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Supplementary Table S6 from Osimertinib and Selpercatinib Efficacy, Safety, and Resistance in a Multicenter, Prospectively Treated Cohort of EGFR-Mutant and RET Fusion-Positive Lung Cancers

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posted on 2023-04-25, 13:40 authored by Julia Rotow, Jyoti D. Patel, Matthew P. Hanley, Helena Yu, Mark Awad, Jonathan W. Goldman, Hovav Nechushtan, Matthias Scheffler, Chih-Hsi S. Kuo, Senthil Rajappa, Guilherme Harada, Sarah Clifford, Alison Santucci, Laura Silva, Rebecca Tupper, Geoffrey R. Oxnard, Jennifer Kherani, Alexander Drilon

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ARTICLE ABSTRACT

Acquired RET fusions have been reported at resistance to treatment with EGFR inhibitors in EGFR-mutant non–small cell lung cancer (NSCLC); however, a multicenter cohort of patients with EGFR-mutant lung cancers treated with osimertinib and selpercatinib for RET fusion–mediated osimertinib resistance has not previously been published. Patients who received selpercatinib in combination with osimertinib on a prospective expanded access clinical trial (NCT03906331) and single-patient compassionate use programs across five countries were centrally analyzed. All patients had advanced EGFR-mutant NSCLC with a RET fusion detected from tissue or plasma following osimertinib therapy. Clinicopathologic and outcomes data were collected. Fourteen patients with EGFR-mutant and RET fusion–positive lung cancers who experienced prior progression on osimertinib received osimertinib and selpercatinib. EGFR exon 19 deletions (±T790M, 86%) and non-KIF5B fusions (CCDC6-RET 50%, NCOA4-RET 36%) predominated. Osimertinib 80 mg daily and selpercatinib 80 mg twice daily were the most commonly administered dosages. The response rate, disease control rate, and median treatment duration were 50% [95% confidence interval (CI), 25%–75%, n = 12], 83% (95% CI, 55%–95%), and 7.9 months (range, 0.8–25+), respectively. Resistance was complex, involving EGFR on-target (EGFR C797S), RET on-target (RET G810S), and off-target (EML4–ALK/STRN–ALK, KRAS G12S, BRAF V600E) mechanisms; RET fusion loss; or polyclonal mechanisms. For patients with EGFR-mutant NSCLC with an acquired RET fusion as a mechanism of EGFR inhibitor resistance, the addition of selpercatinib to osimertinib was feasible and safe and offered clinical benefit, supporting the prospective evaluation of this combination.

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