Niamh Coleman1, Andrew Wotherspoon2, Nadia Yousaf3, Sanjay Popat4. 1. Lung Unit, The Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London, SW3 6JJ, United Kingdom. Electronic address: niamh.coleman@icr.ac.uk. 2. Department of Histopathology, The Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London, SW3 6JJ, United Kingdom. 3. Lung Unit, The Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London, SW3 6JJ, United Kingdom. 4. Lung Unit, The Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London, SW3 6JJ, United Kingdom. Electronic address: sanjay.popat@rmh.nhs.uk.
Abstract
OBJECTIVES: Small cell transformation is a well-recognized mechanism of resistance to EGFR-TKI therapy in EGFR-mutant NSCLC, yet it remains a poorly-described phenomenon in ALK-rearranged NSCLC. MATERIAL AND METHODS: Chart and literature review. RESULTS: We report a case of a patient with ALK-rearranged lung cancer progressing on three-lines of ALK-targeted therapies, with development of acquired resistance to lorlatinib, with both transformation to a neuroendocrine carcinoma, and acquisition of ALK 1196 M. CONCLUSIONS: Given the inevitable development of resistance in ALK + NSCLC, if feasible, re-biopsy on progression should be standard over liquid biopsy. Neuroendocrine carcinoma transformation remains an important mechanism of acquired resistance to lorlatinib.
OBJECTIVES: Small cell transformation is a well-recognized mechanism of resistance to EGFR-TKI therapy in EGFR-mutant NSCLC, yet it remains a poorly-described phenomenon in ALK-rearranged NSCLC. MATERIAL AND METHODS: Chart and literature review. RESULTS: We report a case of a patient with ALK-rearranged lung cancer progressing on three-lines of ALK-targeted therapies, with development of acquired resistance to lorlatinib, with both transformation to a neuroendocrine carcinoma, and acquisition of ALK 1196 M. CONCLUSIONS: Given the inevitable development of resistance in ALK + NSCLC, if feasible, re-biopsy on progression should be standard over liquid biopsy. Neuroendocrine carcinoma transformation remains an important mechanism of acquired resistance to lorlatinib.
Authors: Edyta M Urbanska; Jens B Sørensen; Linea C Melchior; Junia C Costa; Eric Santoni-Rugiu Journal: Int J Mol Sci Date: 2020-04-19 Impact factor: 5.923