Nivolumab plus ipilimumab with chemotherapy as first-line therapy for NSCLC: A single-center real-world experience.

e20630 Background: Dual immune checkpoint inhibition combined with platinum-based chemotherapy has become one of the standard first-line treatment options for advanced non-small cell lung cancer (NSCLC) following the CheckMate 9LA trial. According to our local practice dual immunotherapy is mostly offered to patients with PD-L1-negative tumors. However, real-world evidence on the effectiveness of this regimen remains limited. We report a single-center experience with a particular focus on outcomes in patients with PD-L1-negative disease. Methods: Patients with metastatic NSCLC without actionable driver mutations who received nivolumab plus ipilimumab with platinum-based chemotherapy as first-line systemic therapy between 2020 and 2024 at Moscow City Oncology Hospital No. 62 were retrospectively analyzed. Clinical characteristics, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related toxicity were evaluated. Survival outcomes were estimated using the Kaplan–Meier method and compared by the log-rank test. Cox proportional hazards models were applied to assess associations between clinical variables and outcomes. Results: A total of 184 patients were included; 88% were male. ECOG performance status was 0 in 12%, 1 in 47.2%, 2 in 34.4%, and 3 in 5.6%. Ninety percent received nivolumab plus ipilimumab with carboplatin and paclitaxel, whereas 10% received dual immunotherapy alone. Squamous cell carcinoma accounted for 35% of cases, and adenocarcinoma for 63.3%. PD-L1 expression was < 1% in 72.2%, 1-50% in 23.3%, and > 50% in 3.1% of patients. After a median follow-up of 31.7 months, median PFS was 7.3 months (95% CI, 5.5-9.7), median OS was 16.2 months, and the 3-year OS rate was 23.8%. ORR was 44.5%, including CR in 4.4% and PR in 37.5%; SD was observed in 11.2%. Radiologically confirmed pseudoprogression occurred in 4 patients (2.4%). Median PFS and OS were comparable between PD-L1-positive and PD-L1-negative subgroups: 10.3 versus 8.7 months for PFS (p = 0.99) and 15.9 versus 17.1 months for OS (p = 0.70), respectively. Median OS by objective response was not reached for CR, 23.9 months for PR, 21.3 months for SD, and 12.3 months for PD (p < 0.001). Grade ≥3 adverse events occurred in 24.2% of cases. Patients with grade ≥3 toxicity had longer median PFS (14.1 vs 6.7 months, p = 0.04; HR 0.63 (0.40-0.99) and OS (18.7 vs 12.5 months, p = 0.02; HR 0.57 (0.34-0.93)). Fourteen patients (8.3%) completed 2 years of immunotherapy. Conclusions: In routine clinical practice, nivolumab plus ipilimumab combined with chemotherapy demonstrated clinically meaningful efficacy as first-line therapy for metastatic NSCLC, independent of PD-L1 expression. Development of grade ≥3 toxicity was associated with improved progression-free survival and overall survival.