Efficacy of PD-1/PDL-1 inhibitors for ovarian cancer: a systematic review and network meta-analysis

Abstract

BACKGROUND: Randomized controlled trials (RCTs) have assessed the efficacy of anti-programmed cell death 1 (PD- 1)/programmed cell death ligand 1 (PD-L1), alone or combined with other therapies, for ovarian cancer. However, the optimal strategy remains unclear. This study evaluated their effectiveness as monotherapy and in combination. METHODS: We conducted a systematic review and Frequentist network meta-analysis (NMA) by searching PubMed, ScienceDirect, Web of Science, Scopus, Cochrane Library, and Clinicaltrials.gov databases. This analysis included RCTs comparing PD-L1/PD-1 inhibitors, alone or in combination with other therapies. RESULTS: Six studies involving 3,895 patients and eight treatment combinations were included. PD1/PDL1 inhibitors plus chemotherapy and PD1/PDL1 inhibitors plus ipilimumab showed the greatest progression-free survival (PFS) benefit (hazard ratio (HR) = 0.82, 95% confidence interval [CI]: 0.52-1.07; HR = 0.82, 95% CI:0.51-1.33) and overall survival (OS) (HR = 0.85, 95% CI:0.64-1.14; HR = 0.83, 95% CI:0.45-1.54). These combinations also improved overall response rates (ORR), especially with chemotherapy (OR = 3.06; 95% CI:1.42-6.60). Subgroup analysis suggested that PD-1/PD-L1 inhibitors plus chemotherapy provided the best PFS and OS in PD-L1-positive patients. CONCLUSION: Combining PD-1/PD-L1 inhibitors with chemotherapy or ipilimumab improved survival in ovarian cancer. However, PD-L1 expression may be a valuable biomarker for predicting the efficacy of PD-1/PD-L1 checkpoint inhibitors. REGISTRATION: This systematic review was preregistered in PROSPERO (CRD42022342057). Available from: https://www.crd.york.ac.uk/PROSPERO/view/CRD42022347967.