A study published in The Lancet reports that the anti-PD-1 immunotherapy pembrolizumab significantly improved overall survival in adults with platinum-resistant ovarian cancer when given as part of a chemotherapy/immunotherapy combination with or without a third drug, bevacizumab. The findings from an international clinical trial are reported in the new study led by co-first authors Emese Zsiros, MD, PhD, FACOG, Chair of Gynecologic Oncology at Roswell Park Comprehensive Cancer Center and Nicoletta Colombo, MD, PhD, of the European Institute of Oncology in Milan, Italy.

Results of the randomised phase 3 clinical trial, called ENGOT-ov65/KEYNOTE-B96, show that a treatment regimen of pembrolizumab, a type of immunotherapy known as an immune checkpoint inhibitor, plus weekly paclitaxel significantly improved overall survival in ovarian cancer compared to placebo plus chemotherapy with or without bevacizumab.

Ovarian cancer that does not respond to platinum-based chemotherapy remains one of the most difficult forms of the disease to treat. Many patients experience recurrence within 6 months after treatment, and long-term disease control has historically been limited.

“Progress has been difficult to achieve for patients with ovarian cancer that does not respond to platinum-based chemotherapy,” says Dr. Zsiros. “What we’ve learned through this large international effort represents an important step forward in the treatment landscape. The recent approvals of this regimen in both Europe and the U.S. provide an evidence-based immunotherapy option that has been shown to extend survival, with the greatest benefit observed in patients whose tumours express PD-L1 with what we call a CPS, or a combined positive score of 1 or higher.”

The U.S. Food and Drug Administration (FDA) granted approval of the regimen in February of this year, and its European counterpart, the European Medicines Agency (EMA), followed suit on April 2. The FDA approval specifies the use of pembrolizumab (Keytruda) in combination with the chemotherapy paclitaxel and bevacizumab, a targeted therapy, for patients whose tumours become resistant to platinum-based chemotherapy and who test positive for the biomarker PD-L1 (CPS ≥1). The PD-L1 requirement is included in the approval because the greatest benefit was seen in PD-L1-positive patients who took part in the clinical trial. The approval also includes authorisation of the PD-L1 IHC 22C3 pharmDx companion diagnostic to identify eligible patients.

Conducted between 2021 and 2023, the study enrolled 643 patients at centers in 25 countries. Roswell Park was one of only two centers in New York State to participate, and the only one in Upstate New York (NCT05116189).

“In our experience, some patients with platinum-resistant disease achieve durable disease control,” notes Dr. Zsiros.

First approved by the FDA in 2014 for advanced melanoma, pembrolizumab was previously approved for multiple cancer types, including lung, breast, kidney and bladder cancers. For the treatment of ovarian cancer, it is used in combination with paclitaxel, which directly targets cancer cells, with or without bevacizumab, which inhibits the growth of tumour blood vessels.

Participants enrolled in the ENGOT-ov65/KEYNOTEB96 clinical trial were randomly assigned to receive pembrolizumab plus weekly paclitaxel, with or without bevacizumab, or placebo plus weekly paclitaxel, with or without bevacizumab.

At the final analysis, among the 466 patients whose tumours expressed the biomarker PD-L1 (CPS≥1), those treated with pembrolizumab experienced:

• Median progression-free survival of 8.3 months compared to 7.2 months in the placebo group.
• Median overall survival of 18.2 months compared to 14.0 months in the placebo group.

Source: Roswell Park Comprehensive Cancer Center