European Commission Approves Pembrolizumab/Chemotherapy With or Without Bevacizumab for PD-L1+ Metastatic Cervical Cancer

The European Commission has granted an approval to the combination of pembrolizumab (Keytruda) and chemotherapy, with or without bevacizumab (Avastin), for the treatment of adult patients with persistent, recurrent or metastatic cervical cancer whose tumors have a PD-L1 combined positive score (CPS) of 1 or higher.¹

The approval is based on data from the phase 3 KEYNOTE-826 trial (NCT03635567), where pembrolizumab plus chemotherapy with or without bevacizumab demonstrated a statistically significant improvement in overall survival (OS; HR, 0.64; 95% CI, 0.50-0.81; P = .0001) and progression-free survival (PFS; HR, 0.62; 95% CI, 0.50-0.77; P < .0001) vs placebo plus chemotherapy with or without bevacizumab. Furthermore, the pembrolizumab combination elicited an objective response rate (ORR) of 68% (95% CI, 62%-74%) compared with 50% (95% CI, 44%-56%) with the placebo combination.

“After many years of limited progress in developing new treatment options for persistent, recurrent or metastatic cervical cancer, we saw notable improvements in OS in KEYNOTE-826, with a 36% reduction in the risk of death,” said Nicoletta Colombo, MD, PhD, an associate professor at the University of Milan-Bicocca and the director of the Gynecologic Oncology Program at the European Institute of Oncology in Milan, Italy, stated in a press release. “With today’s approval, health care providers in the EU will be able to offer certain patients with advanced cervical cancer a long-awaited immunotherapy option that has shown significant improvement in OS.”

In October 2021, the FDA approved pembrolizumab for use in combination with chemotherapy, with or without bevacizumab, in patients with persistent, recurrent or metastatic cervical cancer whose tumors have a PD-L1 CPS of 1 or higher.²

The multicenter, randomized, double-blind, placebo-controlled KEYNOTE-826 trial enrolled 617 patients with persistent, recurrent, or metastatic cervical cancer who had not received chemotherapy except when used concurrently as a radio-sensitizing agent. Notably, patients were permitted to enroll irrespective of PD-L1 expression status. A total of 548 patients had a PD-L1 CPS of 1 or higher.³

Patients were randomized 1:1 to receive either 200 mg of pembrolizumab or placebo every 3 weeks for up to 35 cycles. All patients received platinum-based chemotherapy (paclitaxel and cisplatin or paclitaxel and carboplatin). Bevacizumab was administered per investigator discretion.

The primary end points of the trial were OS and PFS per RECIST v1.1 criteria. Secondary end points included ORR and duration of response.

Additional data from KEYNOTE-826 showed that patients with cervical cancer whose tumors had a PD-L1 CPS of 1 or higher treated with the pembrolizumab combination had a median OS that was not reached (NR; 95% CI, 19.8 months–NR) compared with 16.3 months (95% CI, 14.5-19.4) in patients treated with the placebo combination.

Patients in the pembrolizumab arm with a PD-L1 CPS of at least 1 had a median PFS of 10.4 months (95% CI, 9.7-12.3) vs 8.2 months (95% CI, 6.3-8.5) in the placebo arm. Additionally, the pembrolizumab combination produced complete response (CR) and partial response (PR) rates of 23% and 45%, respectively, compared with a CR rate of 13% and a PR rate of 37% with the placebo combination.

Clinical trials have evaluated the safety of pembrolizumab in combination with chemotherapy in 3,123 patients with non–small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), esophageal carcinoma, triple-negative breast cancer (TNBC), and cervical cancer at doses of 200 mg, 2 mg/kg of bodyweight (bw), or 10 mg/kg bw every 3 weeks. The most common adverse effects (AEs) of any grade include anemia (55%), nausea (54%), fatigue (38%), neutropenia (36%), constipation (35%), alopecia (35%), diarrhea (34%), vomiting (28%), and decreased appetite (27%).

Rates of grade 3 or higher AEs were similar between the 2 treatments in NSCLC (67% and 66% with the pembrolizumab combination and chemotherapy regimen, respectively), HNSCC (85% and 84%), esophageal carcinoma (86% and 83%), TNBC (78% and 74%), and cervical cancer (82% and 75%).

“Women diagnosed with persistent, recurrent or metastatic cervical cancer often have a low survival rate,” Gursel Aktan, MD, vice president of global clinical development at Merck Research Laboratories, stated in a press release. “The EU approval of this KEYTRUDA regimen for women with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 CPS ≥1 is the first of its kind for an immunotherapy regimen in Europe and is another example of our continued commitment to delivering new therapies for patients with breast and gynecologic cancers.”

References

1. European Commission approves Merck’s KEYTRUDA® (pembrolizumab) plus chemotherapy, with or without bevacizumab, for patients with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1). News release. Merck. April 29, 2022. Accessed April 29, 2022. https://bit.ly/38CBX79
2. FDA approves pembrolizumab combination for the first-line treatment of cervical cancer. News release. FDA. October 13, 2021. Accessed October 13, 2021. https://bit.ly/3lE3vNS
3. Colombo N, Dubot C, Lorusso D, et al. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021;385(20):1856-1867. doi:10.1056/NEJMoa2112435