ESMO 2022 | ESMO highlights: KRAS G12C inhibitors
David Hong, MD, University of Texas MD Anderson Cancer Center, Houston, TX, discusses highlights from the European Society for Medical Oncology (ESMO) 2022 on KRAS G12C inhibitors. Compelling data was presented at ESMO on the combination of KRAS G12C inhibitors with cetuximab plus adagrasib and panitumumab in colorectal cancer, which demonstrated the combination of a G12C inhibitor plus an EGFR antibody can lead to clinical benefit in patients with chemo-refractory colorectal cancer. Additionally, the Phase III CodeBreak 200 (NCT04303780) trial of the RAS G12C inhibitor, sotorasib, versus docetaxel in patients with previously treated advanced non-small cell lung cancer (NSCLC) demonstrated a superior progression-free survival (PFS) and objective response rate (ORR) with sotorasib. This interview took place at Congress in Paris, France.
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Transcript (edited for clarity)
So I was involved in the first G12C inhibitor in clinic, which was sotorasib, which eventually led to approval in G12C non-small cell lung cancer. We just had some very compelling data, both from Mirati and Amgen on the combination of their G12C inhibitors with either cetuximab in the case of adagrasib and panitumumab in the context of sotorasib. And again, it tells us that in that context of colorectal cancer, the combination of a G12C inhibitor plus an EGFR antibody can really lead to clinical benefit in chemo refractory colorectal cancer patients who have G12C, both having high response rates suggesting for real prolonged clinical benefit in PFS and probably in OS...
So I was involved in the first G12C inhibitor in clinic, which was sotorasib, which eventually led to approval in G12C non-small cell lung cancer. We just had some very compelling data, both from Mirati and Amgen on the combination of their G12C inhibitors with either cetuximab in the case of adagrasib and panitumumab in the context of sotorasib. And again, it tells us that in that context of colorectal cancer, the combination of a G12C inhibitor plus an EGFR antibody can really lead to clinical benefit in chemo refractory colorectal cancer patients who have G12C, both having high response rates suggesting for real prolonged clinical benefit in PFS and probably in OS. So it’s exciting to see that since each of these drugs are like my children, you want them to eventually get a job, right?
We will see in the presidential session that’s coming up, the CodeBreak 200, which is the randomized trial of sotorasib versus docetaxel in the second line setting, we know it already is a positive study, but everybody’s anticipating what exactly is the PFS and overall survival and so we’re looking forward to that. And I’m confident that it will deliver. And the next questions are is how do we combine these drugs with other agents such as immune checkpoint inhibitors, other agents that possibly can target the MAP kinase pathway such as SHIP2, SOS, etc… The data is very early and immature for us to make final conclusions, but I’m excited about those combinations since I’m involved in many of those trials and hopefully be back to VJOncology to report our results.
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