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Highlights

From 1995 to 2014, patient survival after kidney transplantation improved overall for pediatric recipients in the United States; however, racial/ethnic disparities in long-term survival worsened over time.

Results from the study will be presented at ASN Kidney Week 2018 October 23-October 28 at the San Diego Convention Center.

San Diego, CA (October 25, 2018) -- Although there have been considerable reductions in disparities in adult kidney transplant outcomes in the United States, a new study found that disparities in long-term patient survival among pediatric kidney transplant recipients have worsened. The findings will be presented at ASN Kidney Week 2018 October 23-October 28 at the San Diego Convention Center.

For the study, Tanjala Purnell, MPH, PhD (Johns Hopkins University School of Medicine) and her colleagues examined information on 3,295 White, 2,049 Black, and 2,073 Hispanic children who received a kidney transplant in the United States between January 1, 1995 and December 31, 2014.

From 1995 to 2014, patient survival after transplantation improved for all recipients; however, racial/ethnic disparities in long-term survival worsened over time. In 1995, compared with White kidney transplant recipients, Black and Hispanic recipients had 11% and 49% reduced risks of death, respectively. In 2014, compared with White recipients, Black recipients had an 84% higher risk and Hispanics had a 29% lower risk.

"In this national study of pediatric kidney transplant recipients, we found that while survival after KT improved overall, disparities in long-term patient survival worsened from 1995 to 2014. ?In stark contrast to prior study findings of reduced racial/ethnic disparities in outcomes for adult kidney transplant recipients, we found that disparities in long-term survival worsened over the last two decades for Black children in the United States," said Dr. Purnell. "Our findings suggest that national strategies to elucidate and intervene on mechanisms driving disparities among pediatric kidney transplant recipients are needed."

Use of angiotensin converting enzyme inhibitor drugs (ACEIs) to lower blood pressure is associated with an increased risk of lung cancer compared with use of another group of blood pressure drugs called angiotensin receptor blockers (ARBs), finds a study in The BMJ today.

The risk is particularly elevated among people using ACEIs for more than five years, say the researchers.

Although the risk for individual patients is modest, ACEIs are widely prescribed, so these small relative effects could translate into large absolute numbers of patients at risk for lung cancer, say the researchers.

ACEIs are effective drugs used to treat high blood pressure (hypertension). Evidence suggests that ACEIs may increase the risk of lung cancer through the build-up of protein-like chemicals called bradykinin and substance P in the lung. These chemicals have been found on lung cancer tissue, and bradykinin may directly stimulate the growth of lung cancer.

However, previous observational studies examining this association are limited and report inconsistent results.

To better understand this possible association, researchers led by Professor Laurent Azoulay at McGill University in Canada analysed UK primary care records for nearly one million patients who started taking a new antihypertensive drug between 1995 and 2015.

Patients were at least 18 years of age, with no previous cancer, and were followed up for an average of 6.4 years, during which time 7,952 cases of lung cancer were identified (a rate of 1.3 per 1000 person years).

After taking account of factors that could potentially influence the findings, including age, sex, weight (BMI), smoking status, alcohol related disorders, and history of lung diseases, use of ACEIs was associated with an overall 14% increased risk of lung cancer compared with ARBs (1.6 v 1.2 cases per 1000 person years).

Associations were evident after five years of use and increased with longer durations of use, particularly in patients who used ACEIs for more than 10 years (31% increased risk).

Although the magnitudes of the observed estimates are modest, the researchers point out that ACEIs are one of the most widely prescribed drug classes, "so these small relative effects could translate into large absolute numbers of patients at risk." As such, they say these findings "should be replicated in other settings, particularly among patients exposed for longer durations."

This is an observational study, so no firm conclusions can be drawn about cause and effect, and the researchers cannot rule out the possibility that other unmeasured factors, such as socioeconomic differences, diet, and family history of lung cancer, may have affected the results.

However, this is the largest study to assess this specific association, and findings remained consistent after further analyses to test the strength of the results.

As such, the researchers conclude that the use of ACEIs is associated with an increased risk of lung cancer, and they call for "additional studies, with long term follow-up, to investigate the effects of these drugs on incidence of lung cancer."

In a linked editorial, Associate Professor Deirdre Cronin Fenton from the Department of Clinical Epidemiology at Aarhus University in Denmark, says although a 14% relative increase in lung cancer incidence might not translate to a large absolute risk, "the findings are important given the considerable use of ACEIs worldwide."

Nonetheless, in an individual patient, concerns about the long term risk of lung cancer "should be balanced against gains in life expectancy associated with use of ACEIs," she writes. "Further studies with long term follow-up are now needed to enhance the scientific evidence on the long term safety of these drugs," she concludes.

The most effective way to prevent life-threatening complications of extreme hypertension in African-Americans with diabetes is to better control their blood pressure, according to a Rutgers study, the largest of its kind.

The study, which appears in Clinical and Experimental Hypertension, included 783 diabetic and 1,001 non-diabetic patients from a New Jersey hospital emergency department that serves predominantly African-American communities. It is the first study to look at the risk factors and prevalence for hypertensive emergencies -- or drastic increases in blood pressure -- in diabetic African-Americans, a population disproportionally affected by complications of high blood pressure.

"Our study found that both diabetics and non-diabetics with hypertensive emergencies had similar rates of severe injury to target organs," said Irina Benenson, a Rutgers School of Nursing assistant professor. "Combined with the fact that diabetics with hypertensive emergency also had significantly higher levels of blood pressure, this suggests that the occurrence of severe damage to vital organs is not because of just diabetes but because of the accompanying severely elevated blood pressure."

According to Benenson, hypertensive emergencies are associated with life-threatening damage to the brain, heart and kidneys. An estimated one percent to two percent of people with high blood pressure will have a hypertensive emergency during their lives, and the likelihood is even higher among people with diabetes.

Benenson said the risk of hypertensive emergencies in diabetic African-Americans was significantly higher in those with cardiovascular conditions, kidney disease and anemia, and that having medical insurance and access to a healthcare provider did not lessen complications of severely elevated blood pressure. The research is consistent with another recent study, which showed that uncontrolled hypertension was associated with a 57 percent increased risk of cardiovascular disease in people with diabetes.

"Given the fact that the presence of severely elevated blood pressure is the strongest driver of damage to vital organs in individuals with diabetes, the most important intervention for preventing hypertensive emergencies would be to better manage patients' blood pressure," said Benenson. "Carefully selected interventions that improve patients' adherence to medications, and strategies that help providers to overcome clinical inertia, or a failure to increase therapy when blood pressure goals are unmet, may potentially reduce target organ damage associated with hypertensive emergencies."

Munich, Germany, 21 October 2018 - A high concentration of multi-strain probiotic helps to reduce mild to moderate episodes of chemotherapy-induced diarrhoea (CID) in cancer patients, according to results of a phase II/III study in India. (1)

Presenting the final results of the study at ESMO 2018 Congress lead investigator, Atul Sharma, Professor of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India, remarked: "This is probably the first large, randomised, placebo-controlled study to look at the role of multi-strain, high dose probiotic in chemotherapy-induced diarrhoea,".

"Though it did not meet its primary endpoint in reducing incidence of grade 3 and 4 diarrhoea [statistical significance was not met], it helped to reduce the incidence of all grades of diarrhoea. The probiotic also helped in reducing levels of inflammatory markers, the significance of which needs to be ascertained," he added.

The incidence of grade 3 diarrhoea episodes was 8.0% for patients on probiotics, and 4.1% for those on placebo (p=0.088); and for grade 4 episodes the respective incidences were 2.0% and 0% (p=0.050). For all grades of diarrhoea, there were 199 and 220 episodes in probiotic and placebo groups respectively (p=0.019). Analysis of serum vascular endothelial growth factor (VEGF), clusterin, and faecal calprotectin showed levels were reduced in patients taking the multi-strain probiotic.

Chemotherapy changes the consistency of the gut microflora and as such it can lead to some serious side-effects. Sharma explained that, "chemotherapy-induced diarrhoea is an under-reported, unpleasant, and sometimes a serious side-effect of chemotherapy. It may be associated with weight-loss, malnutrition, fatigue and malaise, electrolyte imbalance and inability to deliver full dose of chemotherapy on time. It may also cause loss of body fluid resulting into acute renal injury and rarely death."

To determine whether it improved the balance of intestinal flora and as such reduce these side effects, the study investigated the efficacy of a high potency multi-strain probiotic on patients experiencing CID while receiving fluropyrimidines and/or irinotecan-based cancer therapy.

The multi-strain probiotic consisted of 900 billion colony forming units (CFU) sachet of four strains of lactobacillus, three strains of bifidobacteria and one strain of streptococcus thermophiles. Patients were randomised to receive either one sachet of probiotic twice daily (n=145) or one sachet of placebo twice daily (n=146), started 14 days prior to chemotherapy, and continued for two weeks following chemotherapy cycle three. The vast majority of patients were men, approximately 80%; and aged approximately 46 years. There were no increased incidence of infections.

Adding comment on the study for ESMO was Prof. Michal Mego, Head of 2nd Department of Oncology, Comenius University, National Cancer Institute, Bratislava, Slovak Republic, said: "These data suggest that probiotics have potential to be a simple and novel approach in the reduction of chemotherapy-induced diarrhoea, however confirmatory studies are awaited. As probiotics are living microorganisms there is potential risk of iatrogenic infection in immuno-compromised cancer patients, therefore safety data and adverse events associated with probiotic administration could influence their future role in prevention of chemotherapy induced diarrhoea."

Reflecting on the accumulation of evidence for the effect of the gut microbiome on cancer therapy, Prof. John B.A.G. Haanen, CSO Immunotherapy, Netherlands Cancer Institute, Amsterdam and Professor of Translational Immunotherapy of Cancer, Leiden University Medical Center, Leiden, The Netherlands, said: "Due to the effect of the gut microbiome on response and toxicity in cancer patients treated with immune checkpoint inhibitors and the recently initiated trials with faecal transplantation to improve outcome of checkpoint inhibitors, this study is of interest."

"Currently unknown is whether probiotics used in this RCT positively or negatively influence the immune system, and with more patients being treated with immunotherapy, before embarking on large-scale usage of probiotics to reduce chemotherapy-induced diarrhoea, their effect on the immune system should be investigated," he remarked.

We all know that those angry rants on social media can come back to hurt you--and sooner than you think. "Good," positive chat resonates for a few seconds, generally, but negative chat, even in a chat room where exchanges happen more immediately than on Facebook or Twitter, persists for many minutes, new UC Davis research suggests.

"It's not just that this negative chat has a long life," said Seth Frey, an assistant professor of Communication at UC Davis who is the lead author of the study. "But it has a longer effect on the original speaker. Negative people are really hurting themselves."

The findings were published in Behavior Research Methods in October. Researchers looked at hundreds of millions of chat room messages, over many months, in about 600,000 conversations among young people playing a popular online social game. Most of the million participants worldwide were between 8 and 12 years of age.

The data showed that a positive message doesn't just cause changes in others, but ripples back to the original sender. The effects of a sender's message start rippling back quickly, after just two seconds, and continue for a minute. However, chat containing negative messages or words affects others more strongly and continues to ripple back from a chat audience for up to eight minutes on average. The result is a "feedback loop" in which one instance of negativity causes a stream of negativity that continues to perpetuate itself.

Helping users understand how actions can have consequences

Positive and negative statements were measured with a sentiment analysis toolkit typically used for short Twitter posts.

"This work," the report concludes, "can expand the scope of social-influence-based public health policies and ultimately help young people respond maturely to social influences, whether positive or negative, online or offline." Knowing how long negative or positive interactions persist and measuring precisely how much they snowball helps us understand when a helpful administrator should intervene, and for how long they should continue monitoring.

Frey pointed out, as well, that the participants in this study were younger than many social media participants, who would have more complex emotions and political opinions, and more fluent computer skills, that may make these patterns stronger for older populations. The findings show, Frey said, that emotions ripple online in ways that we can't always measure in in-person, one-on-one conversations. "It's really about isolating the effects that your angry and distasteful actions have on you in the future."

Levels of antiphospholipid antibodies, which are associated with rheumatic diseases, are also elevated in myocardial infarction without any autoimmune co-morbidity, a study from Karolinska Institutet in Sweden published in The Annals of Internal Medicine reports.

Antiphospholipid antibodies (aPL) are a group of antibodies that target endogenous tissue, including the fat molecule cardiolipin and the plasma protein β2glycoprotein-I. Cardiolipin is found in the membranes of blood vessel and blood platelet cells, whereas β2glycoprotein-I is found in the blood and is thought to help the body rid itself of dead cells.

The antibodies are common in rheumatic diseases such as SLE and increase the risk of blood clots. Antiphospholipid syndrome (APS) is an autoimmune condition characterised by recurrent blood clots and/or pregnancy morbidities together with chronically elevated levels of antiphospholipid antibodies.

It is unknown how common the antibodies are in patients with myocardial infarction but without any autoimmune co-morbidity. Previous studies have been small and the antibody measurement flawed.

"I've long been convinced that the antibodies are more common than we think and have now been able to analyse their presence in a large patient material," says Elisabet Svenungsson, professor of rheumatology at Karolinska Institutet's Department of Medicine in Solna.

The study involved 800 patients from 17 Swedish hospitals who had suffered their first myocardial infarction and as many matched healthy controls. Their blood was then analysed 6 to 10 weeks after the infarction for three different antiphospholipid antibody types: immunoglobulin G (IgG), M (IgM) and A (IgA). It was found that eleven per cent of the patients had antiphospholipid antibodies against both cardiolipin and β2glycoprotein-I, which was ten times more than the controls.

"It was a surprisingly high proportion of the patients and the levels were also clearly high," says Professor Svenungsson.

However, the increase was only found in the IgG antibodies, the type that is considered most associated with blood clots.

The measurement was done on one single occasion, so it is not impossible that it reflects a temporary reaction to the infarction. However, if the levels of antiphospholipid antibodies remained elevated for a further three months, by definition these patients have APS.

"In which case they should, according to current recommendations, be prescribed lifelong treatment with the anticoagulant warfarin, which reduces the risk of new blood clots," says Elisabet Svenungsson. "This would change the prevailing guidelines for the investigation and treatment of heart attacks."

Munich, Germany, 21 October 2018 - Neoadjuvant erlotinib benefits selected epidermal growth factor receptor (EGFR)-mutated patients who undergo complete resection of stage IIIA-N2 stage non-small cell lung cancer (NSCLC), shows a randomised study comparing erlotinib with gemcitabine plus cisplatin as neoadjuvant treatment, presented at the ESMO 2018 Congress in Munich. (1)

"Our results suggest promise for the use of biomarker-guided neoadjuvant EGFR-tyrosine kinase inhibitor (TKI) treat-ment strategies in stage IIIA-N2 non-small cell lung cancer,' said Dr Yi-Long Wu, Tenured Professor of Guangdong Lung Cancer Institute, Guangzhou, China who is the principal investigator of the CTONG 1103 study.

"This is the first study to demonstrate progression-free survival (PFS) superiority for erlotinib over gemcitabine plus cisplatin chemotherapy in the neoadjuvant/adjuvant setting of stage IIIA-N2 EGFR mutated NSCLC," added Wu.

Results showed that a total of 386 patients from 17 centres in China were screened, and 72 were randomised 1:1 to therapy and included in the intention-to-treat population. The objective response rate (ORR) for neoadjuvant erlotinib versus gemcitabine plus cisplatin chemotherapy was 54.1% (95% CI: 37.2% to 70.9%) versus 34.3% (95% CI: 17.7% to 50.8%) with an odds ratio of 2.26 (95% CI: 0.87-5.84; p=0.092). After neoadjuvant therapy, 83.8% of patients in the erlotinib group and 68·6% in the gemcitabine plus cisplatin group underwent surgery.

Median progression-free survival (PFS) was significantly longer with erlotinib at 21·5 months (95% CI: 19.3-23.6) versus gemcitabine plus cisplatin chemotherapy at 11.9 months (95% CI: 9.1-14.7) with a hazard ratio of 0.42 (95% CI: 0.23-0.76; p=00003). Overall survival is too immature to report, said Dr Wu.

Current treatment strategies for resected stage IIIA-N2 EGFR mutated NSCLC is controversial, explained Dr Wu, but he added that EGFR-TKIs have been shown to improve the prognosis of patients with advanced EGFR-mutant NSCLC.

"Cisplatin-based doublet chemotherapy as neoadjuvant treatment for stage IIIA-N2 NSCLC only gives patients 5% five-year overall survival benefit," said Dr Wu, explaining the unmet medical need in this patient population. "Recently, the CTONG 1104 trial (2) showed for the first time that adjuvant EGFR-TKI gefitinib could improve disease free surviv-al (DFS) by 10 months compared to adjuvant chemotherapy (28.7 months vs 18.0 months) in N1N2 resected NSCLC. This raises the possibility that EGFR-TKIs may play a beneficial role in the neoadjuvant setting for this subgroup."

Grade 3 and 4 toxicities were fewer in the erlotinib arm (0%) compared to the gemcitabine plus cisplatin arm (29.4%).

Commenting on the study for ESMO, Tony Mok, Professor of Clinical Oncology, the Chinese University of Hong Kong, said that this was a long-awaited study on patients with EGFR mutation positive stage IIIA NSCLC. "It has always been tempting to offer neo-adjuvant EGFR TKI to downstage the patient for surgery, but the action stops short in absence of supporting evidence."

"This randomised study is the first to demonstrate improvement in multiple parameters including tumour response rate, resection rate, major pathologic response and PFS with the use of neoadjuvant EGFR TKI followed by adjuvant TKI," he pointed out. He added that, "While the difference between EGFR TKI and chemotherapy is significant, the impact of neoadjuvant EGFR TKI is relatively disappointing. Response rate of 54% is lower than what is expected of TKI in stage IV disease (about 70%), and only 13% of patients had attained major pathologic response. The reason for this is unclear, but one may have to query if duration of neoadjuvant EGFR TKI for 42 days is sufficient. Overall, this im-portant study offers us the rationale to consider neo-adjuvant EGFR TKI. "

(Vienna, October 22, 2018) In the first study of its kind, cannabis oil has been shown to significantly improve the symptoms of Crohn's disease and the quality of life of sufferers but, contrary to previous medical thinking, has no effect on gut inflammation.

In a randomised, placebo-controlled study, researchers from Israel have shown that cannabis can produce clinical remission in up to 65% of individuals after 8 weeks of treatment, but that this improvement does not appear to result from a dampening down of the underlying inflammatory process.

Speaking at UEG Week 2018 in Vienna, lead researcher, Dr Timna Naftali explained, "Cannabis has been used for centuries to treat a wide range of medical conditions, and studies have shown that many people with Crohn's disease use cannabis regularly to relieve their symptoms. It has always been thought that this improvement was related to a reduction in inflammation in the gut and the aim of this study was to investigate this."

The Israeli team recruited 46 people with moderately severe Crohn's disease, and randomized them to receive 8 weeks of treatment with either cannabis oil containing 15% cannabidiol and 4% tetrahydrocannabinol or placebo. Symptom severity and quality of life were measured before, during, and after treatment using validated research instruments. Inflammation in the gut was assessed endoscopically and by measuring inflammatory markers in blood and stool samples.

After 8 weeks of treatment, the group receiving the cannabis oil had a significant reduction in their Crohn's disease symptoms compared with the placebo group, and 65%met strict criteria for clinical remission (versus 35% of the placebo recipients). The cannabis group also had significant improvements in their quality of life compared with the placebo group.

"We have previously demonstrated that cannabis can produce measurable improvements in Crohn's disease symptoms but, to our surprise, we saw no statistically significant improvements in endoscopic scores or in the inflammatory markers we measured in the cannabis oil group compared with the placebo group," said Dr Naftali. "We know that cannabinoids can have profound anti-inflammatory effects but this study indicates that the improvement in symptoms may not be related to these anti-inflammatory properties."

Looking ahead, the research group plans to explore further the potential anti-inflammatory properties of cannabis in the treatment of inflammatory bowel disease. "There are very good grounds to believe that the endocannabinoid system is a potential therapeutic target in Crohn's disease and other gastrointestinal diseases," said Dr Naftali. "For now, however, we can only consider medicinal cannabis as an alternative or additional intervention that provides temporary symptom relief for some people with Crohn's disease.'

Labrador retrievers, the second most popular dog breed in the UK, are vulnerable to a number of health conditions, according to a study published in the open access journal Canine Genetics and Epidemiology.

Researchers at The University of Sydney, Australia, in collaboration with the Royal Veterinary College, London found that the most common health issues in Labrador retrievers over a one-year period were obesity, ear infections and joint conditions.

Professor Paul McGreevy, the corresponding author, said: "Labrador retrievers are reportedly prone to many disorders but accurate information about how common certain health problems are in the general pet population is lacking. This is the first study to include a large number of Labrador retrievers based on records gathered from hundreds of UK vet clinics. It provides owners with information on the issues that they should look out for in Labrador retrievers."

McGreevy added: "One interesting finding from our research is that the average life-span of Labrador retrievers was 12 years, but chocolate-colored Labradors showed a 10% shorter lifespan than black or yellow Labradors. We also found that ear infections and skin diseases were more common in chocolate Labradors than non-chocolate Labradors."

The authors suggest that the higher number of skin and ear infections in chocolate Labradors may be due to genetics. Chocolate color is recessive in dogs, which means that the gene for chocolate color must be present in both the parents for the puppies to be chocolate colored. When targeting chocolate coat color, breeders may be more likely to use only Labradors which carry the chocolate coat gene and the reduced gene pool may include a higher proportion of genes involved in ear and skin conditions.

The authors analyzed data on 33,320 Labrador retrievers in the VetCompass™ Programme, which collects electronic patient data on dogs attending UK veterinary practices. They extracted data on disorder and mortality from a random sample of 2,074 (6.2%) of these dogs.

Professor Paul McGreevy said: "We also found that 8.8% of Labrador retrievers are overweight or obese, one of the highest percentages among the dog breeds in the VetCompass™ database. There were more overweight and obese dogs among male Labradors that had been neutered than amongst those that had not, but there was no such pattern for female Labradors."

The authors caution that the study may under-estimate the true number of dogs with health problems, as the data are likely to include more severely affected animals that require veterinary management and there may be lower reporting of health issues in less affected Labrador retrievers.

Combining a targeted drug with hormone therapy substantially extends survival for women with advanced breast cancer, a major clinical trial has found.

Women taking palbociclib together with hormone therapy lived seven months longer than those on hormone treatment alone - adding to previous data showing the combination could delay the disease's progression.

The drug's benefit was stronger in women who had previously responded to hormone therapy - who lived 10 months longer with the combination treatment.

The international PALOMA-3 clinical trial was led by researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, and involved 144 research centres in 17 countries.

The study was funded by the drug's manufacturer, Pfizer. It is published in the New England Journal of Medicine today (Saturday), and is being presented simultaneously at the European Society of Medical Oncology congress in Munich, Germany.

The clinical trial tested the benefit of adding palbociclib to the hormone therapy fulvestrant in 521 women with advanced, hormone-sensitive breast cancer whose tumours did not have a protein called HER2.

When women with advanced breast cancer stop responding to other treatments, the only option available is chemotherapy, which can have debilitating side-effects.

The trial examined what effect palbociclib had on women's overall survival and whether it could delay their having to receive chemotherapy.

In the new analysis, the researchers found that women who received the combination treatment survived for an average of 34.9 months - 6.9 months longer than those who received fulvestrant and a dummy pill.

Three years after they were enrolled in the study, 49.6 per cent of women who received both palbociclib and fulvestrant were still alive, compared with 40.8 per cent of women who were treated with fulvestrant alone.

In women whose tumours had previously been sensitive to hormone therapy, the benefit of palbociclib was even clearer - with the combination treatment extending survival by 10 months.

In these women, those who were given the combination treatment survived for an average of 39.7 months, compared with 29.7 months in women who received fulvestrant alone.

The group of women given the combination treatment also saw a longer delay until the start of chemotherapy.

For these women, the average time between enrolment in the trial and the start of chemotherapy increased to 17.6 months compared with 8.8 months in women who received fulvestrant alone.

The trial was led by Professor Nicholas Turner, who works within the Breast Cancer Research Division and Breast Cancer Now Research Centre at The Institute of Cancer Research (ICR), and is a Consultant Medical Oncologist at The Royal Marsden.

Researchers at the ICR - a research institute and charity - believe the findings strengthen the case for making palbociclib available to women whose cancer has progressed on prior hormone therapy. It was approved by NICE for women with previously untreated advanced breast cancer in November last year.

Professor Nicholas Turner, Professor of Molecular Oncology at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:

"The development of palbociclib is one of the biggest advances in treatment for women with advanced breast cancer in the last two decades.

"It's incredibly rewarding that the benefits we had previously seen for palbociclib are now translating into such significant extensions in survival. This drug can offer women more precious time with their loved ones and because it is a targeted treatment it is much kinder than chemotherapy, and enables many women to carry on with their lives normally.

"I'm keen to see it available on the NHS for women with breast cancer who have been treated previously with hormone therapy, as well as those with newly diagnosed advanced disease, as soon as possible."

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"Palbociclib is an innovative new drug that targets specific weaknesses in cancer cells, treating breast cancer in a smarter, kinder way than anything that had been available for these women before.

"This important trial provides further evidence that precision therapies for cancer, based on our scientific understanding of tumours, can offer real survival benefits over traditional treatments. It is an illustration too of the way that targeted drugs can be given together in innovative combinations, as a way of tackling cancer's ability to adapt and evolve, and slowing down development of resistance to treatment."

Christine O'Connell, 45, from London, who is being treated with palbociclib and hormone therapy for advanced breast cancer, said:

"My treatment with palbociclib and hormone therapy has been much more manageable than the chemotherapy I received when I was first diagnosed with breast cancer in 2012, with all the unpleasant side-effects.

"Without palbociclib, my breast cancer would probably progress sooner. At some point I might need to move on to chemotherapy, but for the moment, palbociclib is doing the job.

"Palbociclib has allowed me to lead a relatively normal life. I'm able to work part-time, and I can keep up my cycling, which I could never have done had I been on conventional therapy."

Munich, Germany, 20 October 2018 - Treatment with the cyclin dependent kinase (CDK) 4/6 inhibitor palbociclib achieves a clinically meaningful improvement in overall survival in patients with hormone receptor positive (HR+) human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer that has relapsed or progressed on hormonal therapy, according to the final analysis of overall survival results from the PALOMA-3 study reported at ESMO 2018. (1)

Most patients with HR+ breast cancer become resistant to hormonal therapies over time and inhibiting CDK4/6 has been identified as a target for overcoming or delaying resistance to hormonal therapy in advanced HR+/HER2-breast cancer. The prospective, randomised phase 3 PALOMA-3 trial showed that the first-in-class CDK 4/6 inhibitor palbociclib in combination with fulvestrant significantly improved progression-free survival (PFS) in 521 women with HR+/HER2- metastatic breast cancer that had progressed on previous hormonal therapy (2).

The new analysis assessed overall survival (OS), a key secondary endpoint of PALOMA-3, after a median follow-up of 44.8 months in 521 patients with HR+/HER2- advanced breast cancer. The patients had relapsed or progressed on prior endocrine therapy before being randomised to palbociclib (125mg/day orally, schedule 3/1) plus fulvestrant (500mg per standard of care) or placebo plus fulvestrant. Researchers carried out the OS analysis when approximately 60% (n?310) of the 521 patients in the study had died.

Results showed that median overall survival improved by 6.9 months with palbociclib plus fulvestrant (median OS 34.9 months, 95% confidence interval [CI] 28.8-40.0) compared to placebo plus fulvestrant (median OS 28.0 months, 95% CI 23.6-34.6, p=0.043).

The improvement was even greater in patients with sensitivity to prior endocrine therapy, with an absolute improvement in median OS of 10.0 months. Median OS improved significantly by 11.5 months in patients without visceral disease. No new safety signals were observed with longer follow-up.

"Here, we present the first-ever overall survival results from a phase 3 study for a CDK4/6 inhibitor in a pre-planned analysis of the PALOMA-3 trial. Importantly, this is the first report demonstrating that the absolute gain in survival is similar to the absolute gain in progression-free survival in the whole population. Moreover, this prolongation of life is of a large magnitude in patients with prior sensitivity to endocrine therapy, "said lead author Massimo Cristofanilli, Professor of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Feinberg School of Medicine, Chicago, USA.

"This is very important for patients, as it shows that the improvement in PFS observed in previous studies may have a positive impact on overall survival, an ultimate goal of treatment, therefore improving the chance for a long-term life in spite of advanced disease," said Cristofanilli. He added: "The demonstration of a positive impact on OS also provides additional confidence to clinicians and patients as to the benefits of this combination as an appropriate and effective treatment approach."

Commenting on the findings for ESMO, Dr Carmen Criscitiello, European Institute of Oncology Milan, Italy, said: "These data were much awaited, as the clinical benefit obtained with CDK 4/6 inhibitors was incontestable, but there was the hot question whether the PFS benefit translates into OS benefit. This randomised Phase III trial shows for the first time an improvement in OS with a CDK4/6 inhibitor in the metastatic setting for ER+/HER2- breast cancer." However, she added: "The study was unpowered for OS so the data should be cautiously interpreted. Although the results strongly suggest that the PFS benefit may translate into OS benefit, the other trials conducted with CDK4/6 inhibitors will contribute to confirm the estimate of the OS benefit observed in this study."

Dr Matteo Lambertini, ESMO fellow at the Institut Jules Bordet, Brussels, Belgium, agreed: "Collecting mature OS data at longer follow-up from randomised trials that investigated the combination of endocrine therapy and CDK 4/6 inhibitors is crucial to have a clearer understanding on the benefit of these expensive agents. The limited OS data that we had so far from these trials are now supported by the PALOMA-3 updated results, which strongly suggest that this treatment should become widely available for women with advanced HR+/HER2- disease." He said: "Further research is needed to better understand how to optimise the sequencing of the available treatment options in this setting as well as to identify patients who may benefit from endocrine therapy alone."

Looking to the future, Cristofanilli said: "The significant impact of CDK 4/6 inhibitors on disease-free and overall survival in metastatic disease lead us to be excited about the potential of this class of agents in early-stage breast cancer, where our goal is to improve the cure rate. On that front, two large randomised adjuvant trials of palbociclib in early stage breast cancer, PENELOPE-B and PALLAS, are ongoing."

There is new hope for people with an aggressive type of breast cancer, as an immunotherapy trial shows for the first time that lives can be extended in people with triple-negative breast cancer.

New research led by Queen Mary University of London and St Bartholomew's Hospital has shown that by using a combination of immunotherapy and chemotherapy the body's own immune system can be tuned to attack triple-negative breast cancer, extending survival by up to ten months.

The research, which is published today in the New England Journal of Medicine and presented at the European Society for Medical Oncology 2018 Congress in Munich, also showed that the combined treatment reduced the risk of death or the cancer progressing by up to 40 per cent.

Triple-negative breast cancer often affects young women, with many people diagnosed in their 40s or 50s. The standard treatment is chemotherapy, which most patients quickly develop resistance to. If the disease spreads to other parts of the body, survival is often only 12 to 15 months.

The new treatment combines standard weekly chemotherapy with the immunotherapy medication atezolizumab which is given once every two weeks. The combination works by chemotherapy 'roughening up' the surface of the cancer, which enables the immune system to better recognise and therefore fight the cancer as a foreign object.

Author of the trial Professor Peter Schmid, Professor of Cancer Medicine at Queen Mary University of London and Clinical Director of the Breast Cancer Centre at St Bartholomew's Hospital, explained: "These results are a massive step forward. We are changing how triple-negative breast cancer is treated in proving for the first time that immune therapy has a substantial survival benefit. In a combined treatment approach, we are using chemotherapy to tear away the tumour's 'immune-protective cloak' to expose it as well as enabling people's own immune system to get at it.

"Triple-negative breast cancer is an aggressive form of breast cancer; we have been desperately looking for better treatment options. It is particularly tragic that those affected are often young, with many themselves having young families. I'm thrilled that by using a combination of immunotherapy and chemotherapy we are able to significantly extend lives compared to the standard treatment of chemotherapy alone."

Based on the results of this trial this new treatment is currently under review by health authorities and will hopefully become available in the NHS in the near future. In the interim, patients at St Bartholomew's Hospital with triple-negative breast cancer are offered immunotherapy within ongoing trials.

CHICAGO, IL -- A bioelectronic medicine device was effective in reducing pain and fatigue in patients with lupus, according to Feinstein Institute for Medical Research Professor Cynthia Aranow, MD, who will present pilot clinical trial results Tuesday at the American College of Rheumatology/Association of Rheumatology Professional's (ACR/ARHP) Annual Meeting. These initial results offer promise to the 5 million people who battle the chronic and potentially fatal autoimmune disease around the world.

Lupus causes the immune system to lose the ability to differentiate between foreign agents and healthy tissue. The immune system becomes hyperactive, attacking healthy tissue while causing inflammation and damage to joints, skin and internal organs. Musculoskeletal pain is one of the most common lupus symptoms, affecting up to 95 percent of patients and contributing to a reduced quality of life. While there are immune-suppressing drugs that decrease disease flare-ups and inflammation, these drugs are not effective for all patients and are associated with side effects.

Dr. Aranow's study examined the safety and efficacy of vagus nerve stimulation by an innovative, proprietary device developed by researchers in the Feinstein Institute's Center for Bioelectronic Medicine to reduce the pain and inflammation of lupus. The vagus nerve, part of the body's peripheral nervous system, originates in the brain and branches out throughout the body. It controls the heart, lungs and digestive tract and has been found in previous studies to be involved in reducing inflammation.

"Our study shows that vagus nerve stimulation significantly reduced pain and fatigue associated with lupus," said Dr. Aranow. "We will continue to study this therapy and the mechanisms involved."

This study builds on previous Feinstein Institute research in modulating neural pathways with bioelectronic medicine therapies, which have been shown to successfully treat rheumatoid arthritis and hold promise in other diseases and conditions, including paralysis, Crohn's disease and diabetes. The device tested in this study was developed by biotech engineers in the Center for Bioelectronic Medicine's Bioelectronics and Biosensing Lab, led by Assistant Professor Timir Datta-Chaudhuri, PhD.

"We took the stimulation parameters - the frequency, duration and the intensity of the electrical pulses - identified by previous Feinstein Institute studies on the vagus nerve and immune system, and developed an external stimulation device that pulses through the ear," said Dr. Datta-Chaudhuri. "Many bioelectronic medicine devices are surgically implanted, and we wanted to see if an external device would be as effective, providing patients with an alternative to surgery. The initial results here suggest that our device has the potential to help patients. Further studies are needed to confirm this result."

In the study, 12 participants were randomized to receive external stimulation of the vagus nerve through the ear for five minutes per day for four days and six participants to receive sham stimulation of the ear (they were outfitted with the device, but the device did not emit electrical pulses). Their pain scores, disease activity and levels of fatigue were measured before stimulation and again at five and 12 days later. On day five, participants who received stimulation had a significant decrease in pain and fatigue compared to those who had sham stimulation. The results were similar at day 12.

"This study highlights the importance and success of a clinician/engineer partnership to bridge the gap between technology and treatment," Kevin J. Tracey, MD, president and CEO of the Feinstein Institute. "The Feinstein Institute is uniquely committed to this expertise by its leadership in the field of bioelectronic medicine. Advances in molecular mechanisms targeted by bioelectronic technology is improving the lives of patients."

Munich, Germany, 21 October 2018 - Young cancer patients at the crossroads of childhood and adulthood seem to be stuck in a treatment impasse. A study (1) to be presented at the ESMO 2018 Congress in Munich, has highlighted the existence of barriers to the inclusion of 12 to 25-year-olds in both adult and paediatric early phase clinical trials, suggesting a need for more tailored approaches to give this patient population better access to therapeutic innovation.

In Europe, the legal minimum age to participate in adult clinical trials is almost universally 18 years. "We know, however, that certain girls will develop genetically driven breast cancers very early in life: there are no paediatric trials for this disease, yet these patients are systematically barred from participating in the relevant adult trials. The situation is similar for some adolescents with lymphomas or sarcomas, whose tumours often resemble those of adults much more closely than those found in children," said study author Dr. Aurore Vozy, from Gustave Roussy Institut de Cancérologie in Villejuif, France.

In rare cases, adults in their early twenties are also diagnosed with tumours most commonly seen in children. Paediatric clinical trials, meanwhile, typically set an upper age limit of 18 or 21 years.

To assess the availability and accessibility of new treatments to young cancer patients, a review was conducted of all phase I and phase II trials opened at Gustave Roussy between 2012 and 2017 for solid tumours or lymphomas. Over a six-year period, 465 trials were open, but only 65 included teenagers between 12 and 17 years of age. "In other words, patients in this age group had access to less than 15% of all the early phase trials at our institute," Vozy noted.

Among the 389 trials that were not open to adolescents, it was found that 55% could have been relevant for underage patients - 28 trials targeted tumour types that are particularly common among teenagers. "This means that patients have been denied access to innovative medicines which were available at the very centre where they were being treated, and to which they may have had a better response than to conventional therapy," said Vozy.

Out of 62 paediatric trials open at the centre over the same period, over half did not recruit patients between 19 and 25 years old - even though 10 of these trials targeted cohorts of tumour types that also occur in this age group. "Raising the age bar in paediatric trials to 25 years would clearly make sense in certain cases," Vozy observed.

She argued, however, that the more pressing issue is the current age limit in adult trials: "We know that the diseases, toxicities and pharmacology seen in 12 to 17-year-olds are similar to what we find in adults, so it would be feasible to include these patients in adult trials at no additional risk to them." This has already been done successfully in the USA, where the minimum age for trial participation has been lowered to 12 years.

An additional measure to consider, Vozy underlined, is creating dedicated trial cohorts for adolescents within adult trials: "In a context where, today, most phase I trials in oncology are launched with multiple study populations for different tumour types, it would be easy to cater to the specific needs of adolescents by including them in cohorts of their own," she explained. "The main constraint is that trials which include underage patients should only be conducted in centres that also have paediatric services onsite: adolescents may be affected by disease similarly to adults, but they still need to be treated and followed up on by paediatric specialists."

Dr. Giannis Mountzios, ESMO Chair of the joint ESMO/SIOPE Working Group on Cancer in Adolescents and Young Adults (AYA), (2) commented: "The report presented by this group of researchers is a testament to their scientific rigour, providing objective data that was direly needed on this very critical issue. It shows that even at a highly specialised cancer centre like Gustave Roussy, these arbitrary age limits, which have no medical or scientific basis, are widely used and prevent young patients from accessing clinical trials that target their tumour type. The situation is certainly even worse in centres that don't have the same expertise and dedicated services for adolescents and young adults. This is why ESMO created the Cancer in AYA Working Group together with the European Society of Paediatric Oncology in 2016, through which we aim to raise awareness and influence authorities and stakeholders to stop imposing these barriers."

"I am happy to report that we are now starting to see clinical trials open for specific tumour types across several age groups: the recent approval, in both the USA and Europe, of CAR T-Cell therapy for leukaemia and certain types of lymphoma in children and young adults up to 25 years has been a big breakthrough in this regard. However, this is just the starting point of what should be a concerted effort to look at and devise appropriate care strategies for all the patient sub-groups - including women, the elderly and patients with particular medical conditions - that are chronically underrepresented in clinical trials," Mountzios stated.

Munich, Germany, 21 October 2018 - There is growing evidence that drugs approved for the treatment of breast cancer in women are also effective and well tolerated in men, according to the largest real-life study yet to investigate treatment and outcomes in men with breast cancer (1) and two further studies to be reported at ESMO 2018 (2,3).

Approximately one in every 100 cases of breast cancer (1%) occurs in men (4). However, there have been few prospective studies in men, and clinical trials of breast cancer treatments have often excluded men so treatment recommendations are largely extrapolated from the results of clinical trials in women (4).

To learn more about the treatment of breast cancer in men researchers analysed clinical data collected by the Epidemiological Strategy and Medical Economics Metastatic Breast Cancer (ESME MBC) platform (5) between January 2008 and December 2014. This national database collects real-life data from 18 French Comprehensive Cancer Centers for all patients newly diagnosed with metastatic breast cancer starting at least one treatment.

Researchers retrieved the data for men with metastatic breast cancer included in the database and compared their treatment and outcome with those in women. They found 149 men from the total of 16,701 patients (0.89%). The men were slightly older than the women (mean age 68.1 years vs 60.6 years, p

Results showed men received similar treatments to women with metastatic breast cancer. Just under half of those with HR+/HER2-negative breast cancer (45/105, 42.9%) received frontline hormonal therapy: tamoxifen (20/45), aromatase inhibitor + luteinizing hormone releasing hormone (LHRH) analogues (18/45) or others (7/45).

Their median progression-free survival was 9.8 months, which was similar to that seen in a matched group of women (13.0 months, p=0.8) with the same age, breast cancer histology and grade, location of metastasis and adjuvant treatment.

One in four men with HR+/HER2- breast cancer (29/105, 27.6%) were treated with front-line chemotherapy. Their median progression-free survival was also similar to a matched group of women receiving chemotherapy (6.9 months vs 6.3 months, hazard ratio 1.24, 95% confidence interval 0.69-2.23). Overall survival for the whole population of men included in the database was also similar to that for women (41.8 months vs 34.9 months, p=0.745).

"We have reported on one of the biggest series of men with metastatic disease, with comprehensive data on their management and outcome with different types of treatment," said study author Jean-Sebastien Frenel, from the Institut de Cancerologie de l'Ouest, Nantes, France. "We found that most of the men with HR+/HER2- metastatic disease had received frontline chemotherapy and around 40% had received hormonal therapy. Most of the patients receiving hormonal therapy were treated with tamoxifen and the remainder received aromatase inhibitors. But few patients received aromatase inhibitors plus LHRH analogues despite some guidelines recommending that they should be given in combination."

Frénel reported: "The progression-free survival provided by chemotherapy or hormonal therapy was similar in men as in women." In terms of clinical implications, he suggested: "Hormonal therapy should be given to men with HR+/HER2- metastatic breast cancer in the absence of visceral crisis." He added that oncologists should be aware that aromatase inhibitors should not be given without LHRH analogues. The study is continuing and will next assess the prevalence of BRCA mutation in the patient population.

Commenting on the findings for ESMO, Agnes Jager, medical oncologist and associate professor at Erasmus Medical University Cancer Institute, Rotterdam, The Netherlands said: "A recent study looked at tumour characteristics and outcome in a large cohort of men with primary breast cancer but such extensive data on advanced breast cancer in men was missing until now." She added: "This new study shows the prognosis of men and women is similar, which is of great value as this justifies our current clinical practice. We currently treat men with breast cancer in a similar way to women, which is now supported by these data."

Jager noted that although the largest study of its kind, the number of men with breast cancer was still small and data were lacking on the extent of advanced disease, BRAC mutation status and type of chemotherapy. However, she said: "More detailed information and longer-term follow-up will indicate whether there are characteristics or prognostic factors that are specific for men, which will allow us to change practice in the future."

Hormonal treatment

Results from the first prospective randomised trial to assess different hormonal treatments in men with breast cancer (2) showed that levels of estradiol, a form of the hormone estrogen, decreased steeply with a gonadotrophin releasing hormone analogue (GnRHa) plus tamoxifen or the aromatase inhibitor exemestane but increased with tamoxifen alone measured after a 6 months' treatment period.

More than 90% of male breast cancer patients have HR+ disease. Tamoxifen is currently the standard of care hormonal therapy but there is limited data on its efficacy and safety in men and little information on other hormone blocking treatments.

The Male-GBG54 trial randomised 55 men with breast cancer to hormonal therapy with one of three regimens as adjuvant or metastatic therapy for six months: tamoxifen (20mg per day); tamoxifen + gonadotrophin releasing hormone analogue (GnRHa) (subcutaneous every 3 months); exemestane (25mg/day) + GnRHa.

Tamoxifen blocks estrogen from attaching to hormone receptors on cancer cells while exemestane is an aromatase inhibitor that inhibits estrogen synthesis. The use of GnRH analogues in men with breast cancer is controversial but is based on reducing levels of testosterone when used in combination with aromatase inhibitors or antiandrogens (6).

Results reported at ESMO 2018 showed the median level of estradiol increased by 67% at three months and by 41% at six months in men treated with tamoxifen alone. In contrast, estradiol levels decreased by 85% after three months in men treated with a GnRH analogue plus tamoxifen and by 73% in those receiving a GnRH analogue plus exemestane. Estradiol levels continued to be decreased at six months with GnRH analogues plus tamoxifen or exemestane. These therapies were well tolerated with no safety signals.

The researchers also assessed the impact of treatment on quality of life and sexual function in men with breast cancer treated with hormonal therapy for the first time, using a validated questionnaire (Aging Males' Symptoms Scale Questionnaire) and assessment of erectile function (International Index of Erectile Function). Results showed that tamoxifen had little impact on health-related quality of life or erectile function in men with breast cancer while the combination of GnRH analogue plus exemestane had a major adverse effect on both measures.

Lead author Mattea Reinisch, from Klinikum Essen-Mitte, Essen, Germany, said: "We observed a deep and stable decrease of estradiol in patients receiving the combination of tamoxifen or an aromatase inhibitor plus GnRH for six months of therapy within the Male trial. The suppression of peripheral estradiol is a necessary condition for a therapeutic benefit of endocrine therapy in men with breast cancer when receiving an aromatase inhibitor plus GnRH analogue. Within the tamoxifen monotherapy arm, the estradiol values increased. These changes are known from female breast cancer patients and were expected."

Reinisch added: "Tamoxifen monotherapy should be kept as standard hormonal therapy for men with breast cancer. The side-effects are moderate, hardly impairing sexual behavior. The combination with GnRH influenced patients' well-being and erectile function profoundly."

Commenting on the study, associate professor Agnes Jager said: "The authors are to be congratulated with a randomised trial in such a rare study population, which must have been a real effort. However, it is regrettable that the estradiol suppression at 3 months was the primary endpoint. Although it is relevant to know whether and to what extent E2 levels change over time during different endocrine treatment strategies, as far as I know E2 suppression at 3 months is neither a validated nor a clinically useful surrogate endpoint for the efficacy of endocrine treatment."

Jager added: "The finding that tamoxifen without an LHRH agonist led to a pronounced increase of E2 levels after 3 and 6 months of treatment is not new, although the degree of the increase is somewhat unexpected." But she cautioned that the endpoint used in the study did not answer the question of whether an LHRH agonist should be added to tamoxifen in men and further research is needed on this. "Due to the severe side-effects of LHRH agonists in men and the negative impact on quality of life, clarity about this is of great clinical importance."

Prolonging sensitivity to hormonal therapies

The cyclin dependent kinase 4 and 6 inhibitor (CDK4/6 inhibitor) ribociclib plus the aromatase inhibitor letrozole has comparable safety and tolerability as first-line therapy in men with HR+/HER2- advanced breast cancer to that seen in women, according to preliminary results from an international phase 3 trial reported at ESMO 2018 (7).

Most patients with HR+ breast cancer become resistant to hormonal therapies over time so there is a lot of interest in finding treatments to prolong or restore sensitivity. Inhibiting the CDK4/6 has been identified as a potential target for overcoming or delaying resistance to hormonal therapy in advanced HR+/HER2-breast.

The CDK4/6 inhibitor ribociclib is approved for use in combination with an aromatase inhibitor for treating postmenopausal women with HR+/HER2- advanced breast cancer who have received no previous treatment for advanced breast cancer based on results from a trial showing significantly prolonged progression-free survival. However, men were not included in the study.

The international CompLEEment-1 trial included 20 men with HR+, HER2- advanced breast cancer in the first 1008 patients enrolled who completed 56 days of follow-up or discontinued before data cut-off. They were treated on an open-label basis with ribociclib (600mg per day, 3 weeks on/1 week off) plus letrozole (2.5mg/day). Male patients also received concomitant goserelin (3.6mg subcutaneous implant every 28 days). A pre-planned interim analysis was conducted approximately 15 months after the first patient's first visit for the primary outcome of safety and tolerability.

Results reported at ESMO 2018 showed the most frequent adverse events in men were hot flushes (30.0%), neutropenia (20.0%) and constipation (20.0%). Adverse events of grade 3 severity or higher included neutropenia (4 patients, 20.0%), increased alanine aminotransferase (2 patients, 10%) and increased aminotransferase (1 patient, 5.0%). QT prolongation was infrequent, occurring in 3 men (15.0%) and all events were grade 1 or 2.

Just over one-third (35.0%) of men required dose reduction or interruption due to adverse events, while two men discontinued treatment due to adverse events.

"We can conclude in this sub-population of men that the tolerability and the expected toxicity with ribociclib in men is no different to women. And this increases our confidence in data obtained in large trials with women in order to translate the results and the applicability to men," said lead author Claudio Zamagni, Head of Breast and Gynaecological Medical Oncology, Sant'Orsola Malpighi Hospital, Bologna, Italy. The combination of hormonal therapy plus ribociclib should be considered as an option also for male patients with metastatic HR+ HER2- breast cancer," he suggested. He noted that this was the first study to assess the safety of a CDK4/6 inhibitor in men, adding that efficacy data will be reported with longer-term follow-up in the future.

Commenting on the study, associate professor Agnes Jager considered that limitations were the small numbers and the lack of efficacy data at the time of reporting. She said: "As expected, there were no major differences in safety compared to previously published toxicity data for women, with the exception of the prevalence of neutropenia." This was less frequent compared with female breast cancer patients in the MONALEESA 2 study (grade 3/4: 20.0% in men vs 59.3% in women).

Jager suggested that if similar results were shown in other studies, this could be of interest from a mechanistic point of view. "One of the explanations might be that there is a gender-dependent toxic effect on bone marrow. Alternatively, it could be a reflection of different plasma concentrations of ribociclib in men and women," she suggested. If this were the case, efficacy could be lower in man. She continued: "The first step forwards is to compare the outcome between the men and women within the CompLEEment study, as well as cross-comparing with other studies in women."

Summing up the three studies, Dr. Stefan Zimmerman, Centre Hospitalier Universitaire Vaudois, Switzerland, said: "Male breast cancer patients seem to benefit from endocrine therapy to a similar degree as women. Furthermore, these research results add to the current literature suggesting that the addition of GnRH analogues might improve on tamoxifen alone, but studies with clinical endpoints are needed. Lastly, it is urgent that strategies that have proven effective in defering resistance to endocrine therapy in women are explored in men with advanced breast cancer as well, including CDK4/6 inhibitors."