Last Month in Oncology with Dr. Bishal Gyawali: November 2018

By BISHAL GYAWALI MD  Keynote speech There was a very sobering piece in NEJM by the FDA last month in which the authors try to explore what went wrong with the Keynote-183, Keynote-185 and checkmate 602 trials testing PD-1 inhibitors combinations with pomalidomide or lenalidomide and dexamethasone in multiple myeloma. Interim analysis of Keynote 183 and 185 revealed detrimental effects on overall survival (OS) with hazard ratios of 1.61 and 2.06, not explained by differences in toxicities alone. The checkmate 602 trial was also halted in light of these findings and also showed higher mortality in the nivolumab combination arm. In the thoughtful NEJM piece, the authors make at least three important points. First, they question why these PD-1 inhibitors were tested in combination despite their having limited single-agent activity. In fact, a couple of years ago, Vinay Prasad and I asked the same question: why are novel cancer drugs being tested in combination despite having limited activity as a single agent? We found that these drugs, even when ultimately approved, provide relatively low value and recommended that drugs with poor single agent activity not be tested in combinations unless there are specific reasons to expect synergy. The second important point in the article is that many cancer drug approvals are lately based on durable response rates in single arm trials without a control group, a situation in which it is difficult to evaluate the safety and efficacy ...
Source: The Health Care Blog - Category: Consumer Health News Authors: Tags: Pharmaceuticals Physicians Bishal Gyawali Cancer drugs cancer immunotherapy Clinical Trials FDA Oncology PD-1 inhibitors Source Type: blogs