Pembrolizumab Plus Chemotherapy With or Without Bevacizumab Consistently Improves Survival in Advanced Cervical Cancer Subgroups

Results from the phase 3 KEYNOTE-826 trial show a significant survival benefit with pembrolizumab plus chemotherapy with or without bevacizumab in most patient subgroups with persistent, recurrent, or metastatic cervical cancer.

Pembrolizumab (Keytruda) plus chemotherapy with or without bevacizumab (Avastin) for patients with persistent, recurrent, or metastatic cervical cancer led to consistenly improved overall survival (OS) and progression-free survival (PFS) in a subgroup analysis, according to data from the phase 3 KEYNOTE-826 trial (NCT03635567) presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

KEYNOTE-826 randomized patients to receive 200 mg pembrolizumab once every 3 weeks for up to 35 cycles and paclitaxel plus cisplatin or carboplatin once every 3 weeks, with or without 15 mg of bevacizumab once every 3 weeks, vs placebo once every 3 weeks plus paclitaxel plus cisplatin or carboplatin once every 3 weeks, with or without 15 mg bevacizumab once every 3 weeks. Eligible patients had persistent, recurrent, or metastatic cervical cancer that was not amenable to curative treatment, no prior systemic chemotherapy, and an ECOG performance status of 0 to 1. The stratification factors included metastatic disease at diagnosis, PD-L1 combined positive scores (CPS; <1 vs 1 to <10 vs ≥10), and planned bevacizumab use (yes or no).

KEYNOTE-826 had 2 primary dual end points of OS and PFS, and secondary end points of objective response rate, duration of response, and safety.

In the current subgroup analysis, 617 patients were randomly allocated to receive either pembrolizumab plus chemotherapy, with or without bevacizumab, or placebo plus chemotherapy, with or without bevacizumab.

In the treatment arm, 308 patients were allocated and 307 patients were treated. In the placebo arm, 309 patients were allocated and treated. Median follow up was 22.0 months (range, 15.1-29.4 months).

“PFS in the all-comer population benefited when pembrolizumab was integrated in the regimen, including histology, the type of platinum use selection, nonselection of bevacizumab, and prior chemoradiation only,” Tewari, a professor in the Division of Gynecologic Oncology, Obstetrics, & Gynecology School of Medicine, the University of California Irvine, said.

Investigators reported in the all-comer, squamous cell carcinoma population (n = 447), the median PFS in the treatment arm was 10.4 months (95% CI, 8.4-12.1) vs 6.9 months in the control arm (95% CI, 6.2-8.3). Among the non-squamous cell carcinoma population (n = 169), median PFS was 11.6 months (95% CI, 9.1-23.3) in the treatment arm and 8.4 months (95% CI, 7.0-10.4) in the control arm.

Regarding platinum use, median PFS among patients who received carboplatin was 10.2 months in the treatment arm (95% CI, 8.3-10.6) and 7.4 months in the control arm (95% CI, 6.3-8.4). Among patients who received cisplatin, median PFS was 15.2 months in the treatment arm (95% CI, 10.5-not reached ) and 8.4 months (95% CI, 6.4-12.3) in the control arm.

When bevacizumab was added to the regimen, median PFS in the treatment arm was 15.2 months (95% CI, 10.5-21.3) and 10.2 months in the control arm (95% CI, 8.3-12.3). Without bevacizumab, median PFS was 6.3 months in the treatment arm (95% CI, 6.1-8.3) and 6.2 months in the placebo arm (95% CI, 4.4-6.3).

Median PFS in patients who received prior chemoradiation was 10.3 months in the treatment (95% CI, 8.1-12.6) compared with 6.3 months in the control arm (95% CI, 5.0-6.4). In patients who did not receive prior chemoradiation, the median PFS was 10.4 months in the treatment arm (95% CI, 8.9-12.6) compared with 8.4 months in the control arm (95% CI, 8.2-10.2).

Turning to OS, Tewari said, “Similar to progression-free survival, the benefit conferred with the use of pembrolizumab also improved OS in all the key subgroups including histology, platinum use, bevacizumab use, and prior chemoradiation treatment.” He added that similar results were observed for the subpopulation with the CPS of 1 or greater.

Baseline characteristics for the all-comer population were well balanced between the arms. In the treatment arm (n = 308), 76.3% of patients had squamous cell carcinoma, and in the control arm (n = 309), 68.3% of patients had squamous cell carcinoma. In the treatment arm, 88.6% of patients had a PD-L1 CPS of 1 or greater. In the control arm, 89.0% of patients had a PD-L1 CPS of 1 or greater. Bevacizumab was used in 63.6% of patients in the treatment arm and in 62.5% of patients in the control arm.

Tewari noted that adding pembrolizumab resulted in a generally consistent benefit across a broad selection of key patient subgroups, including those defined by histology, platinum use, bevacizumab use, and prior chemoradiation treatment exposure only.

“We feel that these results represent a snapshot of real-world experiences to help provide additional support for the incorporation of checkpoint immunotherapy, specifically pembrolizumab, for women with recurrent metastatic and persistent cervical cancer,” Tewari concluded.

Reference

Tewari KS, Colombo N, Monk BJ, et al. Pembrolizumab + chemotherapy +/- bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer: Subgroup analysis of KEYNOTE-826. J Clin Oncol. 2022;40(suppl 16):5506. doi: 10.1200/JCO.2022.40.16_suppl.5506