Is there any role for re-biopsy and NGS for patients with NSCLC and KRAS G12C at time of progression after first line therapy before starting sotorasib, or after progression on sotorasib?

This is a great question and one that will come up more frequently. There clearly is a role for biopsy at the time of progression on targeted therapies in other driver alterations in NSCLC, and in limited data; to date, we know that occasionally there are resistance mechanisms to KRAS inhibitors that may be targetable (including BRAF, ALK, RET, MET as well as non-targetable acquired KRAS mutations: Awad et al., PMID 34161704). So in terms of the second question, I certainly would advocate for rebiopsy/liquid biopsy if feasible.

For the first question, for me, it would depend primarily on the timing/duration of first line therapy. I am thinking of those patients who have had durable responses to first line treatment, or stop treatment due to...