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Efficacy of PD-1/PDL-1 inhibitors for ovarian cancer: a systematic review and network meta-analysis
Narjisse Ahmadi1,2,3, Chaimae Kadi2,3,4, Maryam Benlamari1,2,3
1Medical Biotechnology Laboratory (MedBiotech), Bioinova Research Center, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco.
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.
Insights
Combining anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapies with chemotherapy or ipilimumab shows promise for ovarian cancer survival. PD-L1 expression may predict treatment effectiveness in patients.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Ovarian cancer treatment efficacy of anti-PD-1/PD-L1 therapies remains unclear.
- Assessing anti-PD-1/PD-L1 agents alone and in combination is crucial for optimal ovarian cancer management.
Purpose of the Study:
- To evaluate the effectiveness of anti-PD-1/PD-L1 therapies in ovarian cancer.
- To compare monotherapy versus combination strategies involving PD-1/PD-L1 inhibitors.
Main Methods:
- Systematic review and Frequentist network meta-analysis (NMA).
- Searched multiple databases including PubMed, Scopus, and Clinicaltrials.gov.
- Included randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitors in ovarian cancer.
Main Results:
- Six studies with 3,895 patients and eight treatment arms were analyzed.
- PD-1/PD-L1 inhibitors plus chemotherapy or ipilimumab demonstrated the most significant progression-free survival (PFS) and overall survival (OS) benefits.
- Combinations, particularly with chemotherapy, improved overall response rates (ORR).
- Subgroup analysis indicated superior PFS and OS for PD-1/PD-L1 inhibitors plus chemotherapy in PD-L1-positive patients.
Conclusions:
- Combination of PD-1/PD-L1 inhibitors with chemotherapy or ipilimumab enhances survival in ovarian cancer.
- PD-L1 expression serves as a potential biomarker for predicting response to PD-1/PD-L1 checkpoint inhibitors.
