Survival outcomes of PD1/PDL1 inhibitor-based regimens in unresectable stage IIIB, IIIC, and IV non-small cell lung cancer.

e20569 Background: The five-year survival for patients with unresectable Stage IIIB and IIIC non–small cell lung cancer (NSCLC) ranges from 12% to 26%, decreasing to 16% in Stage IV. The introduction of PD-1/PD-L1 inhibitors has changed the therapeutic approach for advanced NSCLC. We aimed to evaluate the survival outcomes of PD-1/PD-L1 inhibitor-based regimens in unresectable Stage IIIB, IIIC, and IV NSCLC. Methods: We conducted a retrospective analysis of adults with unresectable NSCLC treated with PD1/PDL1 inhibitors at a community-based Southern U.S. Health System from 2018 to 2024. Patients were categorized into PD1/PDL1 inhibitor Monotherapy (Group A), Dual-Modality with a PD1/PDL1 inhibitor plus chemotherapy (Group B), and Intensified Multi-agent Therapy (Group C), which included patients who received more than one agent: PD1/PDL1 inhibitors, anti-VEGF, or CTLA4 inhibitor with or without chemotherapy (Group C). A log-logistic survival model adjusted for sociodemographic and comorbidities was used to estimate the adjusted event time ratio (aETR). Results: A total of 133 patients met the inclusion criteria and were categorized into three treatment groups: A (21%), B (64.7%), and C (14.3%). The median age across the three groups was 72 years, 67 years, and 64 years, respectively. The most common PD1/PDL1 inhibitor was pembrolizumab in Groups A (67.9%) and B (67.4%). In Group C, 68.4% received more than one PD1/PDL1 inhibitor, and durvalumab was the most common agent (47.4%). PDL1 expression of more than 50% was seen in 69.2%, 29%, and 11.8% of Groups A, B, and C, respectively. The median survival was 16.2, 10.3, and 24.7 months. Mortality peaked earliest in Group B and latest in Group C during the duration of therapy. The survival model showed no significant difference in the expected survival between Groups A and B (aETR=1.66, 95% CI 0.92–2.99, P>0.05), Groups B and C (aETR=0.53, 95% CI 0.28–0.99, P=0.1), and Groups A and C (aETR=0.88, 95% CI 0.4–1.91, P>0.05). In patients with metastatic disease, the median survival was 16.2, 11.0, and 29.1 months. Mortality peaked earliest in Group B and latest in Group C. The survival model showed no significant difference in the expected survival between Groups A and B (aETR=1.54, 95% CI 0.89-2.66, P>0.05) and Groups A and C (aETR=0.71, 95% CI 0.34-1.51, P>0.05). Group B had a 53.6% lower expected survival (aETR=0.46, 95% CI 0.25-0.87, P=0.047) compared to Group C. Conclusions: Patients with unresectable Stage IIIB, IIIC, and IV non–small cell lung cancer treated with PD1/PDL1 inhibitor monotherapy and multi-agent therapy had longer survival compared to those receiving dual treatment. In patients with metastatic disease, multi-agent therapy had the longest survival of all three regimens. These findings support the benefit of PD1/PDL1 inhibitors. Prospective studies are needed to study its use as direct therapy and as neoadjuvant treatment.