I think of them as a "Chinese menu" where companies can just order "family style" options they choose from the different columns to create their own new trial with their PD1/PD-L1 checkpoint inhibitor of choice. There are so many that will be reported in the next few years, it's essentially impossible to keep track of all of them. The huge collection of trials testing first line immunotherapy in advanced NSCLC will test all of these issues. chemotherapy as first line treatment for patients with advanced NSCLC and PD-L1 expression of 50% or greater in their tumors (the subset of approximately 25-30% of patients who consistently demonstrate the best probability of major tumor shrinkage and prolonged survival from Keytruda and other PD1/PD-L1 checkpoint inhibitors), we already knew that the ground is shifting under our feet. But with literally dozens of first line trials with several agents and subtly different patient populations and comparisons, we have many open questions:ġ) Will immunotherapy agents provide extremely similar results in comparable populations?Ģ) Which patients will truly benefit from immunotherapy more than chemotherapy? All patients, most, or only a rather selected subset with the highest predicted probability of immuno-sensitivity?ģ) Will checkpoint inhibitors be most helpful when administered as single agents in first line, combined with chemotherapy, or potentially combined with other immunotherapy agents?Ĥ) Do immune checkpoint inhibitors need to really be administered indefinitely, or can patients do just as well with a limited duration of therapy followed by sustained benefit?ĥ) Will the lower bar of improved progression-free survival in first line treatment translate to the more valuable prize of prolonged overall survival, particularly after patients have the benefit of crossing over from one treatment to another? In other words, does the timing of treatment matter significantly, so that it's important to administer immunotherapy in the first line setting rather than later? Based on the preliminary report that the Keynote 024 trial of the PD1 inhibitor Keytruda (pembrolizumab) vs. The transition of PD1 and PD-L1 inhibitors into the first line setting for at least some patients with advanced non-small cell lung cancer (NSCLC) is poised to be the biggest sea change in the management of lung cancer over the next 1-2 years.
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