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Efficacy and Safety of Durvalumab and Tremelimumab in Metastatic Non-Small Cell Lung Cancer: A Systematic Review and
Ikhwan Rinaldi1,2, Eric Ricardo Yonatan2, Tasia Esterita2
1Division of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia Jakarta Indonesia.
Purpose:
Immune checkpoint inhibitors have transformed treatment strategies for metastatic non-small cell lung cancer (mNSCLC). This study aimed to assess the efficacy and safety of durvalumab combined with tremelimumab compared with those of standard chemotherapy, particularly in patients with low or negative PD-L1 expression, and in the overall population.
Methods:
A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA 2020 guidelines. Pooled efficacy and safety outcomes were calculated as hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs).
Results:
Three RCTs (n = 1859) were included. Durvalumab and tremelimumab significantly improved overall survival (OS) compared with that of chemotherapy (HR = 0.81, 95% CI: 0.67-0.99) in patients with PD-L1 < 1%. Progression-free survival (PFS) and objective response rate (ORR) were not significantly different in the overall population compared with those in the patient cohort. Treatment-related adverse events (TRAEs) and grade ≥ 3 TRAEs were significantly lower in patients receiving the drug combination (RR = 0.78 and 0.64, respectively), whereas serious TRAEs were higher (RR = 1.41, 95% CI: 1.14-1.74) when compared with those receiving standard chemotherapy. No significant differences were observed in treatment-related deaths.
Conclusions:
Durvalumab plus tremelimumab may be a promising alternative to chemotherapy in patients with mNSCLC with low PD-L1 expression for improving OS, although the PFS and ORR benefits were not significant in the overall population. This combination has a favorable safety profile, although it is associated with a higher risk of serious TRAEs. Further studies are required to confirm these findings. PROSPERO Protocol Registration: CRD420250652760.
