Haematology+Oncology_News

Vol. 9 • No. 1 • 2016 • H aematology & O ncology N ews NEWS 7 ASCO Genitourinary Cancers Symposium 2016

Higher BMI linked to better metastatic RCC outcomes

advantage for higher BMI in this cohort, they did find that higher BMI was significantly as- sociated with lower FASN expression levels (P =  0.034), and that FASN expression below the median level was associated with better overall survival (P = 0.002). Finally, they examined biospecimens from the IMDC dataset with information about outcomes under targeted therapy. Here, they found that FASN staining was associated with prognosis groups, but was not an independ- ent prognostic factor for OS in multivariable analysis. “BMI, however, is associated with overall survival independently of FASN,” Dr Albiges said. Although the mechanisms for the effect of BMI on survival are not clear, the study supports observations that many oncologists have made in clinic, said Dr Ulka Vaisham- payan, chair of genitourinary oncology at the Karmanos Cancer Institute at Wayne State University in Detroit. “There is obviously, I think, a clinical gestalt that we all have, that people who are not los- ing a lot of weight are in general doing better across a number of malignancies,” she said. Dr Vaishampayan was the invited discussant.

GenomeAtlas (TCGA, a joint repository of the National Cancer Institute and National Hu- man Genome Research Institute), expression of FASN, a gene that encodes for fatty acid synthase, was associated with overall survival (OS), but in other samples FASN expression was not an independent prognostic factor for OS, she said. Investigate and verify To clarify the role of BMI in mRCC, Dr Al- biges and colleagues looked at data from clini- cal trials, specimens from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), and biologic data from the TCGA. As the group reported at the 2014 ASCO annual meeting (Abstract 4576), they first looked at the effect of low BMI (< 25 kg/m 2 ) vs high BMI ( ≥ 25) in 1,975 patients with mRCC in clinical trials, and found that af- ter adjustment for IMDC prognosis groups, higher BMI was associated with better OS (median 25.6 months vs 17.1 months; hazard ratio, 0.84; P = 0.0079) and longer time to treatment failure (median 8.1 vs 5.7 months; HR, 0.86; P = 0.0067). They then, in collaboration with Pfizer Oncology, conducted an external validation

BY NEIL OSTERWEIL Frontline Medical News

study using data on 4,657 patients with mRCC treated in phase II–III clinical trials from 2003 through 2013. After adjustment for various risk factors, they found again that BMI of 25 or greater was associated with better outcomes in terms of overall survival (23.4 vs 14.5 months; HR, 0.830; P = 0.0008), progression free survival (8.2 vs 5.5 months; HR, 0.821; P < 0.0001), and overall response rate (25.3% vs 17.6; ad- justed odds ratio, 1.527; P < 0.0001). Dr Albiges noted that when patients were stratified by histologic subtype, “the favourable outcome associated with high BMI was only observed in clear cell RCC.” The investigators next looked at informa- tion from the TCGA dataset on patients with metastatic clear cell RCC to see whether there was correlation between BMI and survival and between BMI and FASN expression. Although they did not detect a significant survival There is obviously, a clinical gestalt that we all have, that people who are not losing a lot of weight are in general doing better across a number of malignancies.

T alk about a paradox: high body mass index is a known risk factor for renal cell carci- noma, but previous studies have shown that patients with high BMI who develop localised RCC generally present with lower grade disease and have better outcomes than normal-weight patients. Now, investigators confirm that overweight or obese patients with metastatic renal cell carcinoma (mRCC) also tend to have a better prognosis than their leaner counterparts when treated with targeted therapies. “We externally validate that BMI impacts the outcome of patients with metastatic kidney cancer treated with targeted therapy in terms of overall survival, progression-free survival, and overall response rates,” said Dr  Laurence Albiges, a visiting scientist in the Kidney Can- cer Centre at the Dana-Farber/Brigham and Women’s Cancer Centre, Boston. Although the mechanism for a protective ef- fect of excess weight is not clear, there is some evidence to suggest that fatty acid metabolism in mRCC may play a role, she said at the 2015 Genitourinary Cancers Symposium. In tissues samples from The Cancer

Risk of lethal prostate cancer is lower for regular aspirin users

really don’t know what they were taking,” he said. “More work is needed to identify particular subsets of men most likely to benefit from aspirin and to determine the optimal aspirin dose,” Dr Allard said. In terms of applying the findings to clinical care, he recom- mended an individualised approach. “The main thing to keep in mind is that although aspirin is over the counter, there are side effects and potential harms. That being said, we don’t have the results of a randomised clinical trial looking at aspirin for prostate cancer survival yet,” he said. So men who are inter- ested in aspirin for prevention of lethal prostate cancer should talk to their physicians, he added, “and look at their personal risks of side effects and harms from aspirin, as well as their benefits in terms of both prostate cancer and also potential cardiovascular benefits. It needs to be a personalised decision for every individual patient.” Dr Sumanta Pal, ASCO spokesperson and moderator of the press briefing, agreed that the trial left unanswered some

critical questions and that clinicians must weigh the potential harms of aspirin therapy against the observed benefits. “While this work is provocative, it’s important to keep in mind that the findings were from an observational study in which surveys and a review of hospital records were used to obtain in- formation,” added Dr Pal, a medical oncologist at City of Hope in Duarte, California. “These studies are certainly thought provok- ing but are perhaps best followed by formal clinical trials where we compare use of aspirin either to no treatment or perhaps to placebo.” Dr Allard disclosed that he had no conflicts of interests. The Pros- tate Cancer Foundation and the National Institutes of Health/ National Cancer Institute funded the trial. Dr Pal disclosed that he receives honoraria from Astellas Pharma, Medivation, and Novartis; that he has a consulting or advisory role with Aveo, Genentech, Myriad Pharmaceuticals, Novartis, and Pfizer; and that he receives research funding from Medivation.

BY SUSAN LONDON Frontline Medical News

R egular aspirin use appears to protect against the develop- ment of metastatic and fatal prostate cancer, according to an analysis of the Physicians’ Health Study. Investigators led by Dr Christopher Brian Allard analysed data from 22,071 male physicians who were initially free of prostate cancer and were prospectively followed from 1982 through 2009. Results showed that after adjustment for age, race, body mass index, and smoking status, men who took aspirin regu- larly (more than three tablets a week) were 24% less likely to develop lethal prostate cancer, which was defined in the study as metastatic disease or death from prostate cancer, Dr Allard reported in a press briefing held before the 2016 genitourinary cancers symposium. However, regular aspirin use did not reduce the risk of pros- tate cancer overall, of high-grade prostate cancer, or of locally advanced prostate cancer. Further analyses restricted to the men who developed pros- tate cancer showed that regular aspirin use after diagnosis was associated with a 39% lower risk of dying from the disease. In contrast, use before diagnosis did not have a protective effect. “Our study demonstrates that regular aspirin intake may inhibit lethal prostate cancer, probably by preventing cancer progression,” said Dr Allard, a urologic oncology fellow at Brigham and Women’s Hospital and Massachusetts General Hospital, both in Boston. Also, “men with prostate cancer who took aspirin regularly after diagnosis had a significantly reduced risk of death.” Although aspirin’s exact mechanism in preventing lethal disease is unknown, preclinical data have implicated its anti- platelet action, which is consistent with evidence suggesting that circulating cancer cells may use platelets to escape im- mune detection, he said. “That would explain why there is no effect on the local cancer, but it is preventing deposition of metastases into metastatic environments.” The main shortcoming of the research was the lack of informa- tion on aspirin dose, DrAllard acknowledged.Although the Physi- cians’ Health Study began as a randomised trial in 1982 testing 325mg of the drug every other day, it was formally stopped 5 years later after cardiovascular benefit was established, and participants were free to take any dose thereafter. “We think most men started at 325 [mg] but then 81 mg did become a popular dose, and we

© ASCO/Todd Buchanan 2016