Can't win 'em all.

Top Line: Hold on a minute, did the KEYNOTE trial consortium somehow miss advanced esophagogastric cancer and hepatocellular carcinoma (HCC)? Why of course not.
The Study: We've got two new KEYNOTE trials to start off your day, and we sure hope it’s going to get better from here. KEYNOTE-061 compares pembro to paclitaxel in previously treated advanced esophagogastric cancer, while KEYNOTE-224 is a nonrandomized trial of pembro after sorafenib in HCC. Let’s go ahead and rip off the bandaid with the randomized 061 trial where patients with esophagogastric cancer that progressed on platinum/fluorouracil received either pembro or paclitaxel. There was no difference in overall survival, but pembro had an embarrassing median progression free survival of 1.5 months, as opposed to 4 months with paclitaxel, and this was among patients with PD-L1 expression. In the 224 trial, as in many prior immunotherapy trials, a small proportion of patients achieved a response (16%) with the rest having stable disease (44%) or progression (40%). What both of these trials and their accompanying editorials really achieve is reminding us of serious unanswered questions regarding how and why immunotherapy works great for certain cancers and sucks wind for others.
Bottom Line: Pembrolizumab had disappointing results in advanced esophagogastric cancer and HCC, underscoring our evolving understanding of immunotherapy efficacy across individual patients and cancer sites. Zhu, Lancet Oncol 2018 & Shitara, Lancet 2018


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