Even for Merck’s oncology powerhouse Keytruda, the emerging role of immunotherapies in gynecological cancer treatment represents a bit of a mixed bag. 

While earlier this year Keytruda seemed to shine in treating cervical cancer, the drug later missed the mark in a study of newly diagnosed endometrial cancer patients. Now, with additional data revealed at this year’s European Society for Medical Oncology (ESMO) Congress, the therapy's benefits across two different settings have become clearer. 

The FDA approved Keytruda to treat patients with stage 3 to 4a cervical cancer alongside chemotherapy in January based on the first interim analysis of Merck’s phase 3 KEYNOTE-A18 trial, making the drug the first PD-1 approved to tackle the disease setting. 

A few months later, the company reported that the drug met the overall survival (OS) endpoint in newly diagnosed patients with high-risk locally advanced cervical cancer, making it the first immunotherapy-based regimen to demonstrate a statistically significant improvement in keeping that patient group alive longer.

At ESMO, Merck presented results from the second interim analysis showing that the 36-month OS rate of patients who took Keytruda along with concurrent chemoradiotherapy (CCRT) was 82.6%, compared to 74.8% with CCRT and placebo.

The benefit in terms of improved overall survival "should change our practice as soon as possible,” Isabelle Ray-Coquard, M.D., president of the French group d’Investigateurs national evaluation des cancers de l’ovaire (Le GINECO), said in an ESMO-provided press release. “Immunotherapy plus chemoradiotherapy provides a new standard of care for patients with high-risk locally advanced cervical cancer.”

Meanwhile, the KEYNOTE-B21 study evaluated Keytruda as an adjuvant therapy in newly diagnosed, high-risk endometrial cancer and measured the drug’s impact on disease-free survival (DFS). That endpoint refers to the length of time after primary treatment ends that a patient survives without signs or signs of their cancer.

Merck reported in May that Keytruda failed to make a statistically significant impact on the DFS measure, so overall survival was not formally tested. The results presented at ESMO show that in the study, DFS events were evenly matched in the Keytruda and the placebo arms at a rate of 22%.

Keytruda didn't make a difference in two-year DFS rates either, which were estimated at 75% for Keytruda patients and 76% for those taking placebo.

However, a subgroup analysis revealed that Keytruda did make for clinically meaningful DFS improvements for patients with mismatch repair deficient (dMMR) tumors. In that population, the DFS risk-reduction rate was 69%

The findings in the dMMR subgroup offers a “powerful example that identifying a good biomarker enables us to change a patient’s story definitively,” Elene Mariamidze, M.D., head of the Georgian School of Oncology, noted in a statement facilitated by ESMO.

Keytruda has been pushing ahead in gynecological cancers for years now and has several indications to show for it, which largely apply to specific subgroups. In 2021, the drug became the first immunotherapy cleared to treat cervical cancers. 

As for endometrial cancers, Keytruda rivals GSK’s PD-1 inhibitor Jemperli. A June approval in patients with primary advanced or recurrent endometrial cancer marked Keytruda’s 40th in the U.S.