May 11, 2026
Post TTLC 2026: Dr. Patel asks how the next step differs based on whether the patient received osimertinib monotherapy, FLAURA2, or MARIPOSA, and how progression pattern, CNS involvement, and re-biopsy guide decisions, including which patients should get stereotactic body radiation therapy (SBRT) and which need a histologic diagnosis to rule out small cell transformation.
Dr. Doroshow describes a tiered approach. For clear, slow oligoprogression in a patient unwilling to undergo re-biopsy, she uses radiation, working with a radiation oncology colleague well-versed in systemic options. Multifocal, significant, or rapid progression should prompt repeat biopsy. Patients with baseline TP53 and RB1 co-mutations are at extremely high risk for small cell transformation and should always be re-biopsied. She stresses CNS protection on osimertinib.
Dr. Patel echoes that a baseline RB1 mutation combined with rapid growth — new lesions and a primary tumor that has doubled in size — should prompt work-up for small cell transformation. When transformation is confirmed, he continues osimertinib alongside cytotoxic chemotherapy rather than dropping the EGFR TKI. His rationale is that not all lesions transform simultaneously; the underlying disease remains clonal for EGFR, so removing targeted pressure risks losing control of the residual adenocarcinoma component. He draws an analogy to prostate cancer, where clinicians maintain hormonal suppression even after small cell transformation emerges.
On CNS surveillance, Dr. Patel obtains brain MRI with each CT scan, every 2 to 4 months. Dr. Doroshow notes NCCN guidance is limited for patients without a brain metastasis history, but she still surveils every 3 months in patients with prior brain metastases and every 3 to 6 months otherwise.
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