Phase II study of multidisciplinary therapy combined with pembrolizumab for patients with synchronous oligometastatic non-small cell lung cancer: TRAP-OLIGO study (WJOG11118L).

8571 Background: Several clinical trials have demonstrated that local ablative therapy (LAT) to all lesions, including primary site, may provide a survival benefit for patients with oligometastatic non-small cell lung cancer (NSCLC). However, few studies have evaluated the efficacy of integrating immune checkpoint inhibitors with chemotherapy and LAT. This study aimed to evaluate the efficacy of multimodal therapy combining platinum-doublet chemotherapy plus pembrolizumab followed by LAT to all sites of disease in patients with synchronous oligometastatic NSCLC. Methods: This multicenter, single-arm, phase II trial enrolled treatment-naive patients with stage IV NSCLC and three or fewer metastatic lesions. Patients received 4 cycles of induction therapy consisting of pembrolizumab plus platinum-doublet chemotherapy. Patients then received LAT to all residual lesions, followed by maintenance therapy with pembrolizumab. The primary endpoint was the 24-month progression-free survival (PFS) rate from the initiation of LAT. Secondary endpoints included safety, response to induction therapy, PFS, overall survival (OS), and the proportion of patients who underwent LAT. The threshold and expected 24-month PFS rates were set at 25% and 60%, respectively, with a one-sided alpha of 0.025 and 80% power. Results: Between October 30, 2020, and August 12, 2022, 30 patients were enrolled. At enrollment, seven patients had one metastasis (23.3%), 14 had two (46.7%), and 9 had three (30%). Twenty-three patients (76.7%) received LAT to all residual disease sites. The 24-month PFS rate from the initiation of LAT was 56.5% (95% CI, 34.3–79.8%). The median PFS from the initiation of LAT was 25.8 months (95% CI, 11.7–not reached). The OS rates at 24 and 36 months from the initiation of LAT were 78.0% (95% CI, 55.0–90.2%) and 61.6% (95% CI, 37.2–78.9%), respectively. During the LAT phase, grade 3/4 adverse events occurred in 3 patients (13.0%). No treatment-related deaths were observed. Conclusions: The TRAP-OLIGO study met its primary endpoint with the lower limit of the 95% CI exceeding the threshold, demonstrating that multimodal therapy combining platinum-based chemotherapy plus pembrolizumab and LAT provides favorable efficacy for patients with synchronous oligometastatic NSCLC. These findings suggest that this integrated approach is a promising treatment strategy for this population. Trial registration: Japan Registry of Clinical Trials, jRCTs041200046. Clinical trial information: jRCTs041200046 .