Comparative Effectiveness of Nivolumab and Ipilimumab Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy in PD-L1 Negative Metastatic Non-Small Cell Lung Cancer Patients.

Background: Recently, the combination of nivolumab, ipilimumab and chemotherapy (NIC) became available for the treatment of metastatic non-small cell lung cancer (mNSCLC) patients, introducing a new treatment option. This study aimed to compare the treatment response and real-world outcomes of NIC with the current standard of care pembrolizumab plus chemotherapy (PC) in PD-L1 negative mNSCLC patients treated in clinical practice and to compare these outcomes with the results of the Checkmate-9LA trial.

Methods: All mNSCLC patients with PD-L1<1% treated with NIC or PC at 2 large teaching hospitals in the Netherlands between 2019 and 2023 were included. The objective response rate (ORR) and progression-free survival (PFS) and treatment characteristics of patients treated with NIC were compared to those of patients treated with PC. Additionally, the real-world outcomes of NIC were compared to the results from the CheckMate 9LA trial. A multivariate Cox regression was used to calculate PFS hazard ratios (HR).

Results: PD-L1 negative mNSCLC patients treated with NIC had a higher ORR than those treated with PC (41% versus 27%, P = .08). The PFS was slightly longer for patients treated with NIC versus PC (5.5 vs. 4.5 months, aHR = 0.91 [95% CI 0.59-1.58]), although not statistically significant. The treatment discontinuation rates were comparable between the real-world NIC and PC cohorts (72% vs. 68%), mostly due to disease progression (67% vs. 64%). The outcomes for patients treated with NIC in clinical practice were comparable to the Checkmate-9LA trial.

Conclusion: For mNSCLC patients with <1% PD-L1 expression, the treatment responses to NIC were numerically better than to PC. Larger cohorts with longer follow-up periods and overall survival endpoints are needed to further establish the role of NIC in PD-L1 negative patients.