(FDA.gov) June 17, 2020 - On June 16, 2020, the Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA, Merck & Co., Inc.) for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. Today, the FDA also approved the FoundationOneCDx assay (Foundation Medicine, Inc.) as a companion diagnostic for pembrolizumab.Read Article
Howard S. Hochster, MD (Posted: June 19, 2020)
Another, but far more problematic approval for Pembro. Which tumors actually have high TMB but not MSI-H? Out of 750+ screened, 102 fit this category for mutations of > 10 mut/MB but only 70 if the cutoff is 13. For the 102, most of the tumors were SCLC, followed by cervix, endometrial and anal cancer. These basically had about a 30% RR but many of these would receive anti-PD1 anyway. It would be useful to know how many of these are hypermutated tumors due to POLE and similar mutations. All in all, this is likely to be a very rare happening in any tumor where we aren't already using anti-PD1 as SOC.