In cases where EGFR NSCLC has transformed into small-cell lung cancer after treatment with osimertinib, and with no CNS involvement, is it advisable to continue osimertinib alongside chemotherapy?
Do you continue EGFR inhibition in patients with EGFR mutated lung adenocarcinoma that progress on 3rd gen TKI and transform into small cell lung cancer?
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There is a paucity of data to guide treatment decisions in this context. Transformed small cell lung cancer is a complex phenomenon wherein some oncogene-driven lung cancer clones undergo a series of transcriptomic and epigenetic changes (such as EMT-like changes and methylation-driven events) as a mechanism of resistance (Oh et al., PMID 39150541; Gardner et al., PMID 38330136). While the presence of TP53 and Rb1 loss increases the risk of small cell transformation in EGFR mutant NSCLC (Offin e...
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Also, tarlatamab doesn’t work well in these despite high DLL3 expression, per this small series Cooper et al., PMID 41166675.
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