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Dual Checkpoint Inhibition With or Without Chemotherapy in Metastatic NSCLC: A Reconstructed Individual Patient Data
Skyler Taylor1, Isadora Mamede2, Gabriela Gazzoni3
1Division of Hematology & Medical Oncology, Mayo Clinic Arizona, Phoenix, Arizona.
Introduction:
Dual immune checkpoint inhibition (DICI) is an established first-line treatment for metastatic NSCLC. Whether the addition of chemotherapy provides an incremental survival benefit beyond DICI alone remains unclear.
Methods:
We performed a systematic review and reconstructed individual patient data meta-analysis of trials evaluating first-line DICI and DICI plus chemotherapy (DICI-CT) in metastatic NSCLC. Data were reconstructed from Kaplan-Meier curves. Overall survival (OS) and progression-free survival were analyzed using Cox proportional hazards and time-varying models. Prespecified subgroup analyses were conducted according to PD-L1 expression, histology, and STK11 or KEAP1 mutational status.
Results:
Four trials comprising 1654 patients were included (699 receiving DICI-CT and 955 receiving DICI). Median OS was similar between the groups (15.4 versus 15.0 mo, hazard ratio = 0.93, 95% confidence interval: 0.81-1.08). Proportional hazards assumptions were violated, and time-varying analyses suggested modest late survival differences favoring DICI, with higher 5-year OS (19.4% versus 17.1%) and progression-free survival (10.5% versus 8.2%). In STK11-mutated tumors, DICI-CT was associated with a limited early survival benefit that was not sustained over time. No clear differences were observed in KEAP1-mutated tumors.
Conclusions:
The addition of chemotherapy to DICI was not associated with improved survival in an unselected population of patients with metastatic NSCLC. These findings support an individualized approach to the use of chemotherapy in combination with DICI.