Pembrolizumab Improves Surgical Outcomes and Response in Advanced Ovarian Cancer

3D rendering of ovarian cancer: © Dr_Microbe - stock.adobe.com

The combination of pembrolizumab (Keytruda) with neoadjuvant chemotherapy appeared to be feasible and efficacious for patients with high-grade serous cancer (HGSC) that was not completely resectable, signaling the importance of further exploring the role of immunotherapy in this patient population.¹

The phase 2 NeoPembOV study (NCT03275506) evaluated 91 patients with stage IIIC/IV HGSC who were treated with standard-of-care (SOC) carboplatin and paclitaxel with or without pembrolizumab 200 mg every 3 weeks. The study’s primary end point was complete resection rate (CRR) at interval debulking surgery.

Among 61 patients treated with pembrolizumab, the CRR was 74% (1-sided 95% CI, 63%) which exceeded the prespecified 50% threshold and thus achieved the primary end point. The CRR in patients without pembrolizumab was 70% (1-sided 95% CI, 54%).

Secondary end points of the study included completeness of cytoreduction index (CCI) and peritoneal cancer index (PCI) scores, objective response rate (ORR), best response rate (BRR), progression-free survival (PFS), and overall survival (OS).

In the SOC group, 27% of patients had a CCI score of 3 or higher compared with 18% in the investigational group, and PCI scores decreased by a mean of 9.6 in the SOC arm vs 10.2 in the investigational arm.

Regarding response, the ORR in the SOC arm was 60% vs 72% in the investigational arm, and the BRR was 83% vs 90%, respectively.

“The 74% CRR compares favorably with CRRs reported for chemotherapy alone in the EORTC 559711 [NCT00003636] and SCORPION phase 3 [NCT01461850] trials and with results from randomized phase 2 trials evaluating neoadjuvant bevacizumab [Avastin]-containing regimens,” study authors wrote in findings published in Nature Communications.

In SCORPION, a phase 3 study comparing primary surgery vs neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumor load, the complete residual disease rates were 45.5% in patients who had primary surgery vs 57.7% in those who had neoadjuvant chemotherapy (P =.206).² These results signaled a need for further investigation into more effective neoadjuvant strategies, according to study authors.

The median PFS was similar in both arms, with 20.8 months (95% CI, 15.0-25.7) vs 19.4 months (95% CI, 17.0-26.7) in the SOC vs investigational arms, respectively.¹ OS was improved in the investigational pembrolizumab arm with 49.8 months (95% CI, 36.1-not estimable [NE]) compared with 35.3 months (95% CI, 27.1-NE) in the SOC arm.

“Despite the relatively small sample size, this randomized phase 2 trial demonstrates that the integration of pembrolizumab into neoadjuvant therapy is feasible and promising, at least for some HGSCs. Deeper translational research (already envisaged when the trial was designed, including systematic collection of tumor biopsies and blood before and after [neoadjuvant chemotherapy]) will be important in interpreting the impact of the investigational regimen,” study authors concluded.

REFERENCES:

1. Ray-Coquard IL, Savoye AM, Schiffler C, et al. Neoadjuvant and adjuvant pembrolizumab in advanced high-grade serous carcinoma: the randomized phase II NeoPembrOV clinical trial. Nat Commun. 2024;15(1):5931. Published 2024 Jul 16. doi:10.1038/s41467-024-46999-x

2. Fagotti A, Ferrandina G, Vizzielli G, et al. Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): Final analysis of peri-operative outcome. Eur J Cancer. 2016;59:22-33. doi:10.1016/j.ejca.2016.01.017