Pembrolizumab plus chemo called new advanced cervical cancer standard

Adding the checkpoint inhibitor pembrolizumab to conventional chemotherapy in women with persistent, recurrent or metastatic cervical cancer improves both progression-free survival (PFS) and overall survival (OS) relative to chemotherapy alone, according to results of a multinational phase 3 trial. The advantage was observed regardless of concomitant use of bevacizumab.

Because of the substantial OS benefit, “pembrolizumab plus chemotherapy may be the new first-line standard of care for advanced cervical cancer,” reported Nicoletta Colombo, MD, PhD, the director of the Gynecologic Cancer Medical Treatments at the Istituto Europeo di Oncologia, in Milan.

Dr. Columbo reported the results of the trial, called KEYNOTE-826, at the 2021 Congress of the European Society of Medical Oncology (ESMO) (abstract LBA2). The article was simultaneously published (N Engl J Med 2021;385[20]:1856-1867).

In the trial, 617 women with persistent, recurrent or metastatic cervical cancer who had not received a prior systemic therapy for their advanced disease were randomly assigned to receive pembrolizumab (Keytruda, Merck) or placebo. Patients in both groups also received paclitaxel and cisplatin or carboplatin. Concomitant bevacizumab was permitted, and its effect was measured. The dual primary end points were PFS and OS in patients with a programmed death ligand-1 (PD-L1) combined positive score (CPS) of 1 or more, in the intention-to-treat (ITT) population, and in patients with a PD-L1 CPS of 10 or more.

At the first interim analysis, conducted almost six months after the last patients were enrolled, among patients with a CPS of 1 or more, the median PFS was 10.4 months in the pembrolizumab group and 8.2 months in the placebo group, producing a risk reduction of nearly 40% (hazard ratio [HR], 0.62; 95% CI, 0.50-0.77; P<0.001). The median PFS was identical among those in the ITT population, but with an HR of 0.65 (95% CI, 0.53-0.79; P<0.001). Among patients with a CPS of 10 or more, PFS was 10.4 months in the pembrolizumab group versus 8.1 months in the placebo group (HR, 0.58; 95% CI, 0.44-0.77; P<0.001).

At 24 months, OS among patients with a CPS of at least 1 was 53.0% in the pembrolizumab group and 41.7% in the placebo group (HR, 0.64; 95% CI, 0.50-0.81; P<0.001); among the ITT population, it was 50.4% versus 40.4% (HR, 0.67; 95% CI, 0.54-0.84; P<0.001), and among those with a CPS of at least 10, it was 54.4% versus 44.6% (HR, 0.61; 95% CI, 0.44-0.84; P=0.001).

Dr. Colombo noted that the PFS and OS rates were only modestly improved for those with a CPS of 10 or higher, which accounted for 51.4% of the population, relative to the all-comer analysis.

The incidence of grade 3 or higher adverse events was 81.8% in the pembrolizumab arm and 75.1% in the arm randomized to placebo. The most common adverse events were anemia (30.3% vs. 26.9%) and neutropenia (12.4% vs. 9.7%). Although both were more frequent in the pembrolizumab arm, Dr. Colombo pointed out that these patients received more treatment cycles and, therefore, had more treatment exposure.

Game Changer
ESMO-invited discussant Mansoor Raza Mirza, MD, the chief oncologist at Copenhagen University Hospital, in Denmark, observed that a subgroup of about 10% of the population did not seem to derive any benefit from treatment. He said biomarkers are needed urgently because of the expense of the immunotherapy, but he also called this trial “a game changer,” saying the experimental regimen in KEYNOTE-826 “should be—not may be—the new standard of care in advanced cervical cancer.” Clinical Oncology