Pembrolizumab Plus CRT Improves Survival in High-Risk Cervical Cancer

Cervical cancer cells: ©heitipaves - stock.adobe.com

The combination of pembrolizumab (Keytruda) plus chemoradiotherapy (CRT) improved overall survival (OS) in patients with newly diagnosed, high-risk, locally advanced cervical cancer, meeting the primary end point of the phase 3 KEYNOTE-A18 trial (NCT04221945; ENGOT-cx11/GOG-3047).¹

Pembrolizumab plus CRT showed a statistically significant and clinically meaningful improvement in OS vs CRT alone, and the safety profile of pembrolizumab was consistent with pervious reports. Findings will be shared at an upcoming medical meeting and shared with global regulatory authorities.

In January 2024, the FDA approved the combination in this intent-to-treat population, making pembrolizumab the first immunotherapy approved in the group. The approval was supported by the KEYNOTE-A18 trial.

Results from the KEYNOTE-A18 trial were published in the Annals of Oncology and presented at the 2023 European Society for Medical Oncology (ESMO) Annual Congress. A total of 1060 patients were randomized to pembrolizumab and concurrent CRT (n = 529) or placebo and concurrent CRT (n = 531). As of the data cutoff of January 9, 2023, with a median follow-up of 17.9 months (range, 0.9-31.0), the pembrolizumab arm had a 67.8% 24-month progression-free survival (PFS) rate vs 57.3% in the placebo arm, and the median PFS was not reached in either arm (HR, 0.70; 95% CI, 0.55-0.89; P =.0020).^2,3

“At the first interim analysis after 237 events, we reduced the risk of recurrence or death by 30% with a hazard ratio of .70. [These are] early results because again, this is a first interim analysis, but at 2 years and with most of the patients still on treatment, we were able to reduce the risk of recurrence or death by more than 10%,” Bradley J. Monk, MD, FACS, FACOG, gynecologic oncologist with Florida Cancer Specialists & Research Institute, told Targeted Oncology^TM.

About KEYNOTE-A18

KEYNOTE-A18 was open to patients with high-risk, locally advanced, stage IB2 to IIB node-positive or III to IVA disease.⁴

“It was high-risk, locally advanced cervical cancer, but there's no such thing as a low-risk patient who has a tumor like this that can't be resected,” Monk explained. “Patients who get cervical cancer are of a different demographic. More than half of the patients enrolled in [KEYNOTE-A18] are not White. I hope that the FDA sort of follows their consistency and allows this to get reimbursed for all women that have locally advanced cervical cancer, not just the high-risk because there's no such thing.”

The study’s primary end points were investigator-assessed PFS and OS, and secondary end points included PFS per blinded independent central review, OS at 36 months, complete response rate, overall response rate, OS in PD-L1-positive patients, and incidence of adverse events.⁴

REFERENCES:

1. Merck’s Keytruda (pembrolizumab) plus chemoradiotherapy (CRT) significantly improved overall survival (OS) versus CRT alone in patients with newly diagnosed high-risk locally advanced cervical cancer. News release. Merck. March 15, 2024. Accessed March 15, 2024. https://tinyurl.com/4n4mfs9a

2. FDA grants priority review to Merck’s application for KEYTRUDA (pembrolizumab) plus concurrent chemoradiotherapy as treatment for patients with newly diagnosed high-risk locally advanced cervical cancer. News release. Merck. September 20, 2023. Accessed March 15, 2024. https://tinyurl.com/yc5m5wfn

3. Lorusso D, Xiang Y, Hasegawa K, et al. Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: a randomized, double-blind, phase III ENGOT-cx11/GOG-3047/ KEYNOTE-A18 study. Ann Oncol. 2023;34(S2):S1279-S1280. doi:10.1016/j.annonc.2023.10.032

4. Study of chemoradiotherapy with or without pembrolizumab (MK-3475) for the treatment of locally advanced cervical cancer (MK-3475/KEYNOTE-A18/ENGOT-cx11/GOG-3047). ClinicalTrials.gov. Updated March 4, 2024.; Accessed March 15, 2024. https://clinicaltrials.gov/study/NCT04221945