Patterns of progression on first line osimertinib in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC): A Swiss cohort study.

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for patients with EGFR mutated non-small cell lung cancer as first-line treatment. However, treatment resistance inevitably emerges and may present as oligo-progressive disease (OPD) or systemic progressive disease (SPD). The incidence of OPD on first-line osimertinib is unknown. We retrospectively analyzed patients who received first-line osimertinib at 13 Swiss centers. The rate of OPD (PD in ≤ 5 lesions) and treatment outcomes were analyzed. The median age of the 148 patients was 68.2 years (range. 38.0-93.3). There were 62 % females, 83 % with a PS ≤ 1, 59 % never smokers, 57 % of patients with an EGFR exon 19 deletion and 37 % with EGFR p.L858R exon 21. 77 % experienced OPD. Median overall survival (OS) was 51.6 months (95 % CI, 38.4-65.0). Median progression-free survival (PFS) was 19.2 (95 % CI, 14.3-23.5) and 8.7 (95 % CI, 2.8-15.6) months for patients with common and uncommon EGFR mutations. Patients with OPD compared to SPD had a significantly longer time to treatment failure and longer OS of (22.9 vs. 10.8 months, p < 0.001 and 51.6 vs. 26.4 months, p = 0.004, respectively). The most common organ sites of PD were lung (62 %), brain (30 %), lymph nodes (30 %), bone (27 %) and pleura (27 %). Twenty-six patients (45 %) with OPD received local ablative treatment (LAT). The OS of OPD patients with LAT was 60.0 (95 % CI, 51.6-NA) vs. 51.4 (95 % CI 38.4-65.3) months (p = 0.43) without LAT. The rate of OPD of patients receiving first line osimertinib was 77 %. Patients with OPD had a significantly better OS compared to patients with SPD (51.6 vs. 26.4 months). Patients with OPD receiving LAT had the longest median OS (60.0 months).

Informations de copyright

Copyright © 2023. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alexandra Schuler: Takeda (travel support), AstraZeneca (research funding, institutional), Amgen (speakers’ bureau, institutional); Sabine Schmid: Grants (institutional): AstraZeneca, Janssen, BMS; Advisory boards (institutional): MSD, Merck, BMS; AstraZeneca; Travel support: Takeda, MSD, Amgen; Oliver Gautschi: local investigator for a clinical trial with osimertinib by AstraZeneca (all fees paid to institution); Laetitia Mauti: AstraZeneca: research funding, travel and expenses, Advisory Board, speaker's fee; MT Mark: advisory fees from BMS, MSD, AstraZeneca, Roche, Takeda and institutional research grants from AstraZeneca, Gilead, Swiss Cancer Foundation (paid to institution); SI Rothschild: Honoraria (Recipient institutional): Roche Pharma AG, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, MSD Oncology, Novartis, Amgen, Lilly, Eisai, Merck Serono, Pfizer, Takeda, Bayer, Janssen Oncology, Otsuka, PharmaMar, Sanofi. Consulting or Advisory Role (Recipient institutional): AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Eisai, Eli Lilly, Merck Serono, MSD Oncology, Novartis, Roche Pharma AG, Takeda, Amgen, Otsuka, PharmaMar. Speakers’ Bureau (Recipient institutional): Roche Pharma AG, Sanofi/Aventis, Amgen, AstraZeneca, Takeda. Research Funding (Recipient institutional): Abbvie, Bristol-Myers Squibb, AstraZeneca, Boehringer Ingelheim, Merck Serono, Roche Pharma AG. Travel support (Recipient personal): Sanofi. Travel support (Recipient institutional): Roche Pharma AG, Bristol-Myers Squibb, MSD Oncology, AstraZeneca, Takeda, Boehringer Ingelheim, Amgen; Alfredo Addeo: Consulting or Advisory Role: BMS, Astrazeneca, Roche, MSD,Pfizer, Eli Lilly, Astellas, Amgen, Novartis. Speaker Bureau: Eli Lilly,Astrazeneca , Amgen. Grant: Astrazeneca; Christian Britschgi: Advisory Role: AstraZeneca, Pfizer, Roche, Takeda, Janssen-Cilag, Boehringer-Ingelheim, Merck KGaA, Sanofi. Research Funding: Bayer. Travel support: AstraZeneca, Takeda, Amgen; Martin Früh: Research Funding (institutional): MSD, AstraZeneca. Other authors declare that they have no known competing financial interests.