And just like that, adagrasib + cetuximab is no longer FDA approved for KRAS G12C colorectal cancer. The accelerated approval was officially withdrawn September 1 after KRYSTAL-10 failed to confirm benefit. We talked about KRYSTAL-10 when it was presented earlier this year. The phase III randomized 461 patients in 2L to adagrasib + cetuximab vs chemotherapy ± VEGF inhibition. It missed both primary endpoints: ▪️PFS: 7.5 vs 8.1 months, HR 0.89
▪️OS: 21.6 vs 21.7 months, HR 0.83 Hard to argue with a negative phase III trial. But I still like the idea of a chemo free option. Response rate was 47% vs 16%. That could matter for some patients (like those who you need just a little more shrinkage to enable crative intent therapy). KRYSTAL-10 asked whether adagrasib + cetuximab was better than chemotherapy in 2L. It wasn’t. That doesn’t mean the concept of KRAS G12C + EGFR blockade was wrong. And it doesn’t mean there aren’t patients for which this isnt valuable. Anyone celebrating this should look themselves in the mirror; this is a tool that has just been removed from our arsenal. However, the FDA did exactly what the system is designed to do; pull back if the Ph III doesnt pan out after accelerated approval. @OncoAlert @TheGutOncLab @Onco_Nexus