What does this research mean for the field?

HRD/BRCA-driven genomic instability plays a dominant role in treatment response to PARP inhibitor and immune checkpoint inhibitor combination therapy, indicating that PD-L1 negativity alone should not preclude the use of this combination. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the efficacy of combining PARP inhibitors and immune checkpoint inhibitors in patients with PD-L1–negative cancers across various tumor types and genomic backgrounds.

August 27, 2026Immunotherapy

Efficacy of PARP inhibitor and immune checkpoint inhibitor combination therapy in PD-L1–negative cancers: a systematic review and meta-analysis

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Authors

SZSusu ZhouSUNY Upstate Medical University VPVishw PatelSUNY Upstate Medical University NKNoriko KishiKyoto University

Discussion

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Implication

Meta-analysis reveals sustained PARP and checkpoint inhibitor activity in PD-L1-negative tumors with BRCA or HRD alterations, suggesting PD-L1 status alone should not preclude treatment.

Key Points

To evaluate the efficacy of combining PARP inhibitors and immune checkpoint inhibitors in patients with PD-L1–negative cancers across various tumor types and genomic backgrounds.
Conducted a systematic review and random-effects meta-analysis of 22 clinical trials encompassing 1,849 patients, including 718 who were PD-L1-negative (PROSPERO: CRD420251163119).
Evaluated pooled objective response rate (ORR), disease control rate (DCR), and 12-month progression-free survival (12-m PFS), with subgroup analyses stratified by BRCA mutation, homologous recombination deficiency (HRD), and cancer type.
Treatment activity was sustained in tumors harboring BRCA mutations (p=0.643) and HRD positivity, whereas DCR and 12-month PFS were numerically lower in PD-L1-negative cohorts without reaching statistical significance.
Response patterns varied by cancer type: ovarian cancer maintained meaningful clinical responses regardless of PD-L1 expression, while breast cancer exhibited reduced activity and other tumor types showed limited responses.

Cite This Study

Zhou et al. (2026) studied this question.

synapsesocial.com/papers/6a8fea0d10c91c1e926220d5 https://doi.org/10.1080/1750743x.2026.2722581

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Implication

Meta-analysis reveals sustained PARP and checkpoint inhibitor activity in PD-L1-negative tumors with BRCA or HRD alterations, suggesting PD-L1 status alone should not preclude treatment.

Efficacy of PARP inhibitor and immune checkpoint inhibitor combination therapy in PD-L1–negative cancers: a systematic review and meta-analysis

Discussion

Member takes

Implication

Key Points

Cite This Study

Efficacy of PARP inhibitor and immune checkpoint inhibitor combination therapy in PD-L1–negative cancers: a systematic review and meta-analysis

Discussion

Member takes

Implication

Key Points

Cite This Study

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