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• W4385836700 abstract "<div>AbstractPurpose:<p>Acquired <i>RET</i> fusions have been reported at resistance to treatment with EGFR inhibitors in <i>EGFR</i>-mutant non–small cell lung cancer (NSCLC); however, a multicenter cohort of patients with <i>EGFR</i>-mutant lung cancers treated with osimertinib and selpercatinib for <i>RET</i> fusion–mediated osimertinib resistance has not previously been published.</p>Patients and Methods:<p>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 <i>EGFR</i>-mutant NSCLC with a <i>RET</i> fusion detected from tissue or plasma following osimertinib therapy. Clinicopathologic and outcomes data were collected.</p>Results:<p>Fourteen patients with <i>EGFR</i>-mutant and <i>RET</i> fusion–positive lung cancers who experienced prior progression on osimertinib received osimertinib and selpercatinib. <i>EGFR</i> exon 19 deletions (±T790M, 86%) and non-<i>KIF5B</i> fusions (<i>CCDC6-RET</i> 50%, <i>NCOA4-RET</i> 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%, <i>n</i> = 12], 83% (95% CI, 55%–95%), and 7.9 months (range, 0.8–25+), respectively. Resistance was complex, involving EGFR on-target (<i>EGFR</i> C797S), RET on-target (<i>RET</i> G810S), and off-target (<i>EML4–ALK/STRN–ALK</i>, <i>KRAS</i> G12S, <i>BRAF</i> V600E) mechanisms; <i>RET</i> fusion loss; or polyclonal mechanisms.</p>Conclusions:<p>For patients with <i>EGFR</i>-mutant NSCLC with an acquired <i>RET</i> 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.</p><p><i><a href=https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-23-0993 target=_blank>See related commentary by Krebs and Popat, p. 2951</a></i></p></div>" @default.
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• W4385836700 date "2023-08-15" @default.
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• W4385836700 title "Data from Osimertinib and Selpercatinib Efficacy, Safety, and Resistance in a Multicenter, Prospectively Treated Cohort of <i>EGFR</i>-Mutant and <i>RET</i> Fusion-Positive Lung Cancers" @default.
• W4385836700 doi "https://doi.org/10.1158/1078-0432.c.6615935.v2" @default.
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