Phase II study of pembrolizumab plus olaparib in recurrent cervical cancer progressing after platinum-based chemotherapy (GOTIC-025).

OBJECTIVE

Treatment options for recurrent cervical cancer, particularly after platinum-based chemotherapy and immunotherapy, remain limited. However, PD-1 blockade is effective in patients naïve to immune checkpoint inhibitors. Further, PARP inhibition may modulate the tumor immune microenvironment and enhance the efficacy of PD-1 blockade therapy. This study evaluated the efficacy and safety of pembrolizumab plus olaparib for cervical cancer.

METHODS

This multi-center, investigator-initiated, single-arm phase II trial enrolled immunotherapy-naive patients with recurrent cervical cancer who previously received platinum-based chemotherapy. Patients received pembrolizumab (200 mg every three weeks) and olaparib (600 mg daily) until disease progression or unacceptable toxicity. The primary outcome was objective response rate (ORR), and secondary outcomes were progression-free survival (PFS), overall survival (OS) and safety.

RESULTS

Among enrolled 28 patients, 14 had squamous cell carcinoma, 20 received ≥2 prior chemotherapy regimens. Twenty-two patients had prior bevacizumab. Twenty-six patients were evaluable for response. The ORR was 3.8% (90% CI, 0.2%-17.0%); the disease control rate was 50.0%. The median PFS was 3.4 months. No patients required discontinuation of pembrolizumab; 4 patients discontinued olaparib due to adverse events (AEs). All patients experienced AEs with grade ≥ 3 events in 60.7%, and hematologic toxicities were the most common severe events.

CONCLUSIONS

We investigated the combination of pembrolizumab and olaparib in patients with platinum-treated recurrent cervical cancer and demonstrated manageable safety. However, adding a PARP inhibitor to PD-1 blockade showed limited activity in this small cohort. Although the ORR was modest, DCR and median OS were numerically encouraging in this heavily pretreated population.