Mehlman Camille, Swalduz Aurelie, Monnet Isabelle, Morin Clara, Wislez Marie, Guisier Florian, Curcio Hubert, Du Rusquec Pauline, Cortot Alexis B, Gounant Valerie, Abbar Baptiste, Duchemann Boris, Giroux-Leprieur Etienne, Pierret Thomas, Quilot Fleur-Marie, Cadranel Jacques, Fallet Vincent
Department of Pneumology and Thoracic Oncology, Tenon Hospital, Assistance Publique Hôpitaux de Paris and GRC 4, Theranoscan, Sorbonne Université, Paris, France.
Department of Medical Oncology, Léon Bérard Cancer Centre, Lyon, France.
Oncologist. 2024 Dec 26. doi: 10.1093/oncolo/oyae312.
The emergence of diverse resistance mechanisms after osimertinib therapy, including on-target epidermal growth factor receptor (EGFR) mutations and off-target alterations, warrants investigation of novel therapeutics to overcome these challenges and improve patient outcomes.
COMPOSIT was a French, retrospective, multicenter, cohort study of the effectiveness and tolerability of osimertinib in combination with other targeted therapies in patients with advanced EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC) who harbored other oncogenic drivers as primary or acquired resistance mechanisms. Real-world progression-free survival (rwPFS), overall survival (OS), and objective response rate (ORR) were the primary endpoints.
The study included 61 patients (63.9% women; median age, 61 years). Chemotherapy was administered to 26 patients (42.6%) before the combinations. The most frequently targeted resistance mechanisms were MET amplification (n = 40) and BRAF alterations (n = 11). Sixteen combinations of osimertinib with other targeted therapies were reported. Overall (except for 10 patients in clinical trials), median rwPFS and OS were 3.9 (95% CI, 2.9-5.2) and 9.8 months (95% CI, 6.8-14.8). Best ORR (n = 54) was 50% (95% CI, 33.0-72.8). In patients with MET amplification (n = 29), median rwPFS and OS were 4.9 (95% CI, 2.9-7.2) and 8.6 months (95% CI, 5.3-21.6). Grade ≥3 adverse events occurred in 15 patients (24.6%). No deaths were related to treatment.
Combinations of osimertinib with other targeted therapies appeared to be feasible and safe and may offer clinical benefit to overcome resistance to osimertinib in EGFRm NSCLC, especially in patients with MET amplification.
奥希替尼治疗后出现多种耐药机制，包括靶向表皮生长因子受体（EGFR）突变和非靶向改变，这就需要研究新的治疗方法来克服这些挑战并改善患者预后。
COMPOSIT是一项法国的回顾性多中心队列研究，旨在评估奥希替尼联合其他靶向治疗对晚期EGFR突变（EGFRm）非小细胞肺癌（NSCLC）患者的有效性和耐受性，这些患者存在其他致癌驱动因素作为主要或获得性耐药机制。真实世界无进展生存期（rwPFS）、总生存期（OS）和客观缓解率（ORR）是主要终点。
该研究纳入61例患者（63.9%为女性；中位年龄61岁）。26例患者（42.6%）在联合治疗前接受过化疗。最常见的靶向耐药机制是MET扩增（n = 40）和BRAF改变（n = 11）。报告了16种奥希替尼与其他靶向治疗的联合方案。总体而言（临床试验中的10例患者除外），中位rwPFS和OS分别为3.9个月（95%CI，2.9 - 5.2）和9.8个月（95%CI，6.8 - 14.8）。最佳ORR（n = 54）为50%（95%CI，33.0 - 72.8）。在MET扩增患者（n = 29）中，中位rwPFS和OS分别为4.9个月（95%CI，2.9 - 7.2）和8.6个月（95%CI，5.3 - 21.6）。15例患者（24.6%）发生≥3级不良事件。无死亡与治疗相关。
奥希替尼与其他靶向治疗联合似乎可行且安全，可能为克服EGFRm NSCLC对奥希替尼的耐药性提供临床益处，尤其是在MET扩增患者中。
