66 F never smoker presented last year with NSCLC, extensive bone and brain mets.Bx adnoca, NGS EGFR L858R and EGFR T79M both high VAF, EGFR amplification and RET V804M (confirmed to be germline by genetic testing). Treated with osi with initial response but progression after just 6 months. Re biopsy and repeat NGS; Same variant plus MET amplification and DCC deep deletion. Would you rec to target MET ampl, or RET ( selpercatinib vs amivantamab) or just chemo?
I think it is reasonable to keep the osimertinib and target the MET amplification. There are MET targeting agents like crizotinib and tepotinib that you may be able to obtain though, as there is no approval here. The germline mutation is a point mutation not a fusion so I think it is unlikely to be driving the lung cancer.
