Phase 2 study of osimertinib in combination with platinum and pemetrexed in patients with previously untreated EGFR-mutated advanced non-squamous non-small cell lung cancer: The OPAL Study

• Published in: European journal of cancer (1990) 2023-05, Vol.185, p.83-93
• Main Authors: Saito, Ryota, Sugawara, Shunichi, Ko, Ryo, Azuma, Koichi, Morita, Ryo, Maemondo, Makoto, Oizumi, Satoshi, Takahashi, Kazuhisa, Kagamu, Hiroshi, Tsubata, Yukari, Seike, Masahiro, Kikuchi, Toshiaki, Okamoto, Isamu, Satoshi, Morita, Asahina, Hajime, Tanaka, Kentaro, Sugio, Kenji, Kobayashi, Kunihiko
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; EGFR mutation; ErbB Receptors - genetics; Humans; Lung Neoplasms - chemically induced; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Mutation; Non-small cell lung cancer; Osimertinib; Pemetrexed; Platinum - therapeutic use; Platinum-based chemotherapy
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2023.02.023

This multicenter phase 2 trial evaluated the safety and efficacy of osimertinib and platinum-based chemotherapy (OPP) in patients with previously untreated EGFR-mutated advanced non-squamous non-small cell lung cancer (NSCLC). Patients received osimertinib 80 mg once daily (QD), with either cisplatin 75 mg/m2 (arm A) or carboplatin (area under the curve [AUC] = 5; arm B), plus pemetrexed 500 mg/m2 for four cycles and maintenance therapy of osimertinib 80 mg QD with pemetrexed 500 mg/m2 every 3 weeks. The primary end-points were safety and objective response rate (ORR), and the secondary end-points were complete response rate (CRR), disease control rate (DCR), and progression-free survival (PFS). In total, 67 patients (34 in arm A and 33 in arm B) were enrolled between July 2019 and February 2020. At the data cutoff (28th February 2022), 35 (52.2%) patients had discontinued the protocol treatment, including 10 (14.9%) due to adverse events. No treatment-related deaths occurred. In the full analysis set, the ORR, CRR, and DCR were 90.9% (95% confidence interval [CI], 84.0–97.8), 3.0% (0.0–7.2), and 97.0% (92.8–100.0), respectively. Based on updated survival data (data cutoff on August 31, 2022, median follow-up time: 33.4 months), the median PFS was 31.0 months (95% CI, 26.8 months–not reached) and median overall survival was not reached. This is the first study to show that OPP has excellent efficacy with acceptable toxicity in previously untreated EGFR-mutated advanced non-squamous NSCLC patients. •This trial evaluated first-line concurrent osimertinib and cytotoxic chemotherapy.•The combination of osimertinib and cytotoxic chemotherapy was found to be tolerable.•The objective response rate was 90.9% (95% confidence interval, 84.0–97.8).•The median PFS was 31.0 months (95% CI, 26.8 months–not reached).