Pembrolizumab Regimens Earn European Approvals in Gynecologic Cancers

The European Commission’s decision follows positive opinions from the European Medicine Agency’s Committee for Medicinal Products for Human Use recommending the approval of pembrolizumab-based treatment for these gynecologic cancer indications in September 2024.

The European Commission has approved pembrolizumab (Keytruda)-containing regimens for 2 gynecologic cancer indications for patients in the European Union, according to a press release from the developer, Merck.¹

Specifically, pembrolizumab plus carboplatin/paclitaxel received approval as frontline therapy for adults with primary advanced or recurrent endometrial carcinoma who are eligible to receive systemic therapy. Additionally, the European Commission approved pembrolizumab plus chemoradiotherapy (CRT) for adults with previously untreated International Federation of Gynecology and Obstetrics 2014 stage III to IVA locally advanced cervical cancer.

The European Commission’s decision follows positive opinions from the European Medicine Agency’s Committee for Medicinal Products for Human Use recommending the approval of pembrolizumab-based treatment for these gynecologic cancer indications in September 2024.²

“These [pembrolizumab]-based regimens have the potential to change the treatment paradigm for [patients] with endometrial and cervical cancer, 2 of the most commonly diagnosed cancers among [patients] in Europe,” Gursel Aktan, MD, PhD, vice president of Global Clinical Development at Merck Research Laboratories, said in the press release.¹ “These approvals underscore the continued expansion of the use of [pembrolizumab] in diverse patient populations and treatment settings with the utility of [pembrolizumab] ranging from earlier lines of therapy to treating advanced disease.”

The approval for the endometrial carcinoma indication was supported by findings from the phase 3 NRG-GY018/KEYNOTE-868 trial (NCT03914612). Supporting data for the cervical cancer approval came from the phase 3 KEYNOTE A-18 trial (NCT04221945).

KEYNOTE-868 Trial

Prior data from the KEYNOTE-868 trial showed that in a cohort of 591 patients with mismatch repair proficient (pMMR) endometrial carcinoma, pembrolizumab/chemotherapy produced a median progression-free survival (PFS) of 13.1 months (95% CI, 10.5-18.8) vs 8.7 months (95% CI, 8.4-10.7) with chemotherapy alone (HR, 0.54; 95% CI, 0.41-0.71; P <.00001).³ Among 225 evaluable patients with mismatch repair deficient (dMMR) disease, the median PFS was not reached (NR; 95% CI, 30.6-NR) and 7.6 months (95% CI, 6.4-9.9) in each respective treatment arm (HR, 0.30; 95% CI, 0.19-0.48; P <.00001).

In the KEYNOTE-868 trial, patients with stage III, IVA, IVB, or recurrent endometrial cancer were assigned to receive pembrolizumab at 200 mg intravenously every 3 weeks or matched placebo plus paclitaxel at 175 mg/m² and carboplatin at area under curve 5 for 6 cycles followed by pembrolizumab at 400 mg intravenously or placebo every 6 weeks for a maximum of 14 cycles.

The trial’s primary end point was PFS. Secondary end points included overall survival (OS), objective response rate (ORR), duration of response, and safety.

In June 2024, the FDA approved pembrolizumab plus carboplatin/paclitaxel for patients with primary advanced or recurrent endometrial carcinoma based on data from the KEYNOTE-868 trial.⁴

KEYNOTE-A18 Trial

Among patients with stage III to IVA cervical cancer in the KEYNOTE-A18 trial, combining pembrolizumab with CRT reduced the risk of disease progression or death by 41% compared with concurrent CRT alone (HR, 0.59; 95% CI, 0,43-0.82). Additionally, prior data from the trial showed that the pembrolizumab combination reduced the risk of death by 33% (HR, 0.67; 95% CI, 0.50-0.90; P = .0040).⁵

In KEYNOTE-A18, 1060 patients with previously untreated cervical cancer were assigned to receive pembrolizumab at 200 mg intravenously every 3 weeks or matched placebo for 5 cycles plus cisplatin at 40 mg/m² every week for 5 cycles and radiotherapy followed by pembrolizumab at 400 mg intravenously or placebo every 6 weeks for 15 cycles.

The trial’s primary end points were PFS and OS. Secondary end points included the complete response rate, ORR, and safety.

The FDA previously approved pembrolizumab/CRT for those with stage III to IVA cervical cancer in January 2024.⁶ Supporting data for the approval came from the KEYNOTE-A18 trial.

References

1. Merck’s KEYTRUDA® (pembrolizumab) receives 30th approval from European Commission with two new indications in gynecologic cancers. News release. Merck. October 24, 2024. Accessed October 24, 2024. https://tinyurl.com/4z5s2f49
2. Merck receives positive EU CHMP opinions for KEYTRUDA® (pembrolizumab) regimens as treatment for patients with two types of gynecologic cancers. News release. Merck. September 20, 2024. Accessed October 24, 2024. https://tinyurl.com/5a95t3dc
3. KEYTRUDA® (pembrolizumab) plus chemotherapy significantly improved progression-free survival compared to chemotherapy alone as first-line therapy for advanced or recurrent endometrial carcinoma, regardless of mismatch repair status. News release. Merck. March 27, 2023. Accessed October 24, 2024. https://tinyurl.com/c3tv394p
4. FDA approves pembrolizumab with chemotherapy for primary advanced or recurrent endometrial carcinoma. News release. FDA. June 17, 2024. Accessed October 24, 2024. https://shorturl.at/sZ3Xx
5. Merck’s KEYTRUDA® (pembrolizumab) plus chemoradiotherapy (CRT) reduced risk of death by 33% versus CRT alone in patients with newly diagnosed high-risk locally advanced cervical cancer. News release. Merck. September 14, 2024. Accessed October 24, 2024. https://tinyurl.com/47n8z3y2
6. FDA approves pembrolizumab with chemoradiotherapy for FIGO 2014 stage III-IVA cervical cancer. News release. FDA. January 12, 2024. Accessed October 24, 2024. https://tinyurl.com/4c6a7dbx