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oai:recercat.cat:2445/2249722026-04-08T14:08:30Zcom_2072_1057col_2072_478916col_2072_478917

RELAY, Erlotinib Plus Ramucirumab in Untreated, EGFR-Mutated, Metastatic NSCLC: Outcomes by EGFR Exon 19 Deletion Variants Nishino, Kazumi Shih, Jin Yuan Nakagawa, Kazuhiko Reck, Martin Garon, Edward B. Carlsen, Michelle Matsui, Tomoko Visseren Grul, Carla Nadal, Ernest Epigenètica Farmacogenètica Epidemiologia molecular Epigenetics Pharmacogenetics Molecular epidemiology Introduction: EGFR gene mutations are drivers of NSCLC. The RELAY double-blind, placebo (PBO)-controlled phase 3 study revealed superior progression-free survival (PFS) for ramucirumab plus erlotinib (RAM + ERL) versus PBO (PBO + ERL) in patients with untreated advanced NSCLC and an EGFR-activating mutation. This exploratory analysis evaluated potential associations between EGFR exon 19 deletion (ex19del) variants and clinical outcomes. Methods: Patients (N = 449) were randomized (1:1) to RAM plus ERL or PBO plus ERL. Plasma samples were collected at baseline, on treatment, and at 30-day poststudy treatment discontinuation follow-up. Baseline and treatment-emergent gene alterations were investigated by Guardant360 next-generation sequencing. Patients with a valid baseline plasma sample and ex19del were included (RAM + ERL, n = 62; PBO + ERL, n = 72). Results: The most common ex19del variant was E746_A750del (67.2%); EGFR E746 deletions (E746del) occurred more frequently than L747 deletions (74.6% versus 25.4%, respectively). TP53 mutations were the most frequently co-occurring baseline gene alterations. With treatment arms combined, median PFS was 18.0 months versus 12.5 months for patients with uncommon (non-E746_A750del, n = 44) versus common (E746_A750del, n = 90) ex19del variants (hazard ratio [HR] = 1.657 [95% confidence interval or CI:1.044-2.630]). Median PFS was longer with RAM plus ERL versus PBO plus ERL for patients with the common (15.2 versus 9.9 mo; HR = 0.564 [95% CI: 0.344-0.926]) and E746del (15.4 versus 9.9 mo; HR = 0.587 [95% CI: 0.363- 0.951]) variants. Treatment-emergent post-progression EGFR T790M rates were higher in the common versus uncommon and E746del versus L747 deletion subgroups. Conclusions: RAM plus ERL provides benefit and improves treatment outcomes for patients with metastatic NSCLC with EGFR ex19del variants. 2025-12-16T11:25:10Z 2025-12-16T11:25:10Z 2023-12-19 2025-12-05T14:18:21Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2666-3643 https://hdl.handle.net/2445/224972 38304857 eng Reproducció del document publicat a: https://doi.org/10.1016/j.jtocrr.2023.100624 JTO Clinical and Research Reports, 2023, vol. 5, num. 2 https://doi.org/10.1016/j.jtocrr.2023.100624 cc-by-nc-nd (c) Nishino, Kazumi et al., 2023 https://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess 15 p. application/pdf Elsevier BV Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))