How do you treat patients with sensitizing EGFR mutations who progress on osimertinib with small cell transformation, but with persistent EGFR mutation detected in the peripheral blood or tumor?   

There are no studies to directly address this issue. For sure the patient needs chemotherapy with etoposide/platinum. Whether osimertinib should be continued during the chemotherapy or re-instituted after 4 cycles of EP has not been studied. I would give both.

I fully agree with @Paul A. Bunn that the patient should be treated with platinum and etopiside. My experience in half a dozen patients with small cell transformation of EGFR mutant lung cancer has been that the responses are not as deep nor very prolonged compared to de-novo small cell (regula...