Pembrolizumab Plus Chemotherapy Improves OS, PFS in Cervical Cancer

Results from the phase 3 KEYNOTE-826 trial show that the safety profile of pembrolizumab plus chemotherapy was manageable in cervical cancer.

Pembrolizumab (Keytruda) with or without bevacizumab (Avastin) in combination with chemotherapy improved overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent, or metastatic squamous cell carcinoma; adenosquamous carcinoma; or adenocarcinoma of the cervix not treated with prior chemotherapy or amenable to curative treatment, according to results from the phase 3 KEYNOTE-826 trial (NCT03635567) published in the Annals of Oncology.

Data reveal that the dual primary end points of OS and PFS were met. Among all-comers who received bevacizumab, the median PFS in the pembrolizumab arm was 15.2 months (95% CI, 10.5-23.3) vs 10.2 months (95% CI, 8.3-12.2) in the placebo arm (HR, 0.57; 95% CI, 0.45-0.73), including 24-month PFS rates of 41.8% and 24.0%, respectively. Additionally, among all-comers who received bevacizumab, the median OS in the investigational arm was 37.6 months (95% CI, 27.0 – not reached [NR]) vs 22.5 months (95% CI, 16.6-25.0) with placebo (HR, 0.61; 95% CI, 0.47-0.80), including 24-month OS rates of 61.2% and 46.1%, respectively.

Additionally, for all-comers who had not received bevacizumab, the median PFS was 6.3 months (95% CI, 6.1-8.3) vs 6.2 months (95% CI, 4.4-6.3) in the respective arms (HR, 0.69; 95% CI, 0.50-0.94) with 24-month PFS rates of 21.6% and 5.8%. For this patient population, the median OS was 17.1 months (95% CI, 14.4-21.3) vs 12.6 months (95% CI, 10.0-15.7), respectively (HR, 0.67; 95% CI, 0.49-0.91), with 24-month OS rates of 36.1% and 26.2%, respectively.

“In this subgroup analysis of the KEYNOTE-826 study, the addition of pembrolizumab to chemotherapy resulted in clinically meaningful improvements in PFS and OS compared with placebo plus chemotherapy regardless of concomitant bevacizumab use in patients with persistent, recurrent, or metastatic cervical cancer,” Domenica Lorusso, MD, PhD, professor and director of the Operative Unit of Gynecological Oncology at Humanitas San Pio X, and study coinvestigators wrote in the study. “Additionally, objective response rate [ORR] was higher and duration of response [DOR] was longer with the addition of pembrolizumab.”

Investigators of the phase 3 KEYNOTE-826 study randomly assigned patients 1:1 to receive either pembrolizumab (with bevacizumab, n = 196; without bevacizumab, n = 112) or placebo (n = 193, 116) plus chemotherapy. Medical reasons accounted for 75.9% of patients who did not receive bevacizumab. Patient demographics and baseline characteristics were balanced between both arms.

Eligible patients 18 years or older with persistent, recurrent, or metastatic cervical cancer received either 200 mg of intravenous pembrolizumab or placebo once every 3 weeks for up to 35 cycles. Patients additionally received 175 mg/m2 of paclitaxel plus 50 mg/m2 of cisplatin or 5 mg/ml/min of carboplatin area under the concentration-time curve. Patients could also have received 15 mg/kg of intravenous bevacizumab once every 3 weeks per investigator decision.

The study primary end points were PFS per RECIST v1.1 criteria and OS. Secondary end points included ORR, DOR, and safety.

Treatment-related adverse events (TRAEs) in patients who received bevacizumab were reported in 97.4% of the investigational arm vs 98.4% of the placebo arm, including grade 3 or greater occurrences in 74.0% and 66.8% of the respective arms. TRAEs leading to discontinuation occurred in 40.8% and 32.6% of the respective arms, with deaths occurring in 1 and 3 patients, respectively.

Among those who did not receive bevacizumab, TRAEs occurred in 96.4% and 94.8%, respectively; grade 3 or greater instances occurred in 60.4% of the investigational arm and 62.1% of the placebo arm. Treatment-related discontinuations occurred in 19.8% and 12.1% of the respective arms, with 1 death reported in each.

Reference

Lorusso D, Colombo N, Dubot C, et al. Pembrolizumab plus chemotherapy for advanced and recurrent cervical cancer: final analysis according to bevacizumab use in the randomized KEYNOTE-826 study. Ann Oncol. Published online October 9, 2024. doi:10.1016/j.annonc.2024.10.002