Phase 2 study of atezolizumab with carboplatin plus pemetrexed followed by maintenance atezolizumab with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer: CJLSG1902.

8580 Background: Chemotherapy, including immune checkpoint inhibitors and platinum-containing agents, is a standard of care for patients with advanced non-small cell lung cancer (NSCLC). Pembrolizumab in combination with pemetrexed and cisplatin/carboplatin is approved as first-line treatment for patients with metastatic non-squamous NSCLC based on the results of KEYNOTE-189. However, data on the efficacy and safety of this regimen are limited in patients ≥75 years old. On the other hand, the results of the post hoc integrated analysis of IMpower130 and IMpower132 suggest that the efficacy and safety of atezolizumab in combination with platinum-based chemotherapy is maintained in patients ≥75 years old. Methods: This multicenter, open-label, phase 2 trial was conducted at 28 institutions in Japan to evaluate the efficacy and safety of atezolizumab with carboplatin plus pemetrexed followed by maintenance atezolizumab with pemetrexed. Eligible patients had metastatic/recurrent non-squamous NSCLC without sensitizing EGFR or ALK mutations, were aged ≥75 years, had received no prior systemic chemotherapy, and had an ECOG performance status of 0 or 1. For induction therapy, patients received atezolizumab (1,200 mg/body), pemetrexed (500 mg/m 2 ) and carboplatin (area under concentration-time curve 5 mg/mL/min) on day 1 of each 21-day cycle. For maintenance therapy, patients received atezolizumab (1,200 mg/body) and pemetrexed (500 mg/m 2 ) on day 1 of each 21-day cycle. Treatment continued until radiographic progression or unacceptable toxicity was observed. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety. This trial is registered with the Japan Registry of Clinical Trials (jRCTs041200032). Results: From July 2020 to January 2023, 60 patients were enrolled in this study. Median age was 77.0 years (range 75-86), 84.1% of the patients were male, and 25.5% had a PD-L1 TPS ≥50%. The median PFS was 7.49 months (80% CI 5.52-7.75, exceeding the threshold of 5.5 months), and the median OS was 16.82 months (80% CI 14.49-20.93). The ORR was 55.9% (95% CI 42.4-68.8). The most common grade 3 or 4 adverse events were neutropenia (40.7%), leukopenia (35.6%), anemia (35.6%), and thrombocytopenia (30.5%). Serious adverse events were observed in 19 patients (6 with pneumonitis, 6 with febrile neutropenia). No treatment-related deaths were observed. Conclusions: This study met the primary endpoint of PFS. Atezolizumab with carboplatin plus pemetrexed followed by maintenance atezolizumab with pemetrexed showed favorable efficacy and the safety profile was manageable. This combination therapy is an encouraging option as a first-line treatment strategy for elderly patients with metastatic non-squamous NSCLC. Clinical trial information: 041200032 .