ESMO: Pembrolizumab Effective in Metastatic Cervical Cancer

Adding pembrolizumab to standard platinum-based chemotherapy—with or without bevacizumab—significantly improved progression-free survival in women with metastatic cervical cancer, KEYNOTE-826 investigators reported.

“Our data suggest that this may be a new standard-of-care,” Nicoletta Colombo, MD, of the Department of Medicine and Surgery University of Milan–Bicocca, and Division of Gynecologic Oncology, European Institute of Oncology said in a presentation at ESMO 2021 Congress Presidential Symposium. The KEYNOTE-826 findings were also published online by The New England Journal of Medicine.

“We found that adding pembrolizumab reduced the hazard of disease progression, as assessed by investigator review, or death by 38% in patients with a PD-L1 combined positive score of 1 or more, by 35% in the intention-to-treat population, and by 42% in patients with a PD-L1 combined positive score of 10 or more; the hazard of death was reduced by 36%, 33%, and 39%, respectively,” she said.

The researchers enrolled 617 patients with persistent, recurrent, or metastatic cervical cancer and randomized them 1:1 to 200 mg pembrolizumab (n=308) or placebo (n=309) every 3 weeks for up to 35 cycles. All patients also received platinum-based chemotherapy, with or without bevacizumab.

The sample included 548 patients “with a PD-L1 combined positive score of 1 or more (273 in the pembrolizumab group and 275 in the placebo group) and 317 patients with a PD-L1 combined positive score of 10 or more (158 in the pembrolizumab group and 159 in the placebo group),” they wrote. More than 60% of patients had platinum-bevacizumab chemotherapy. The researchers assessed PD-L1 expression during screening.

Among the findings:

• Pembrolizumab-treated patients with a PD-L1 combined positive score of 1 or more survived for a median of 10.4 months versus 8.2 months for similar patients in the placebo arm. The HR for disease progression or death was 0.62 favoring pembrolizumab (P<0.001).
• ITT analysis found a median survival of 10.4 months versus 6.2 months and an HR of 0.65, (P<0.001).
• The median PFS was 10.4 months in pembrolizumab-treated patients with a PD-L1 positive score of 10 versus 8.1 months in the placeb0 group, HR 0.58 (P<0.001).

Mansoor Raza Mirza, MD, chair of the European Network of Gynecological Oncology Trials (ENGOT) group and chief oncologist at Copenhagen University Hospital, who served as the discussant for Colombo’s presentation, called the findings “A game changer… looking at primary endpoints of overall survival and progression-free survival in both the biomarker positive population and the intention to treat population, the curves are clinically significant for both.”

He noted that the first big breakthrough in treatment of metastatic cervical cancer was the introduction of the bevacizumab/platinum doublet, which improved overall survival by a median of 3 months. Since its introduction in 2013-14, it has become the standard of care.

But the introduction of immune checkpoint inhibitors brought a “tsunami of phase III trials,” Mirza noted. For example, he said the findings reported by Colombo serve as a confirmatory trial to the benefit reported in KEYNOTE-158, which assessed pembrolizumab in a variety of solid tumors and demonstrated significant efficacy in cervical cancer.

He pointed out that the study included both squamous cell and adenocarcinoma, but “there is a disbalance in the study that is in the sample size regarding histology: there was no stratification according to histology.” Other checkpoint inhibitor trials have reported only modest activity in adenocarcinoma. In KEYNOTE-826, 24% of patients in the pembrolizumab arm were non-squamous versus 31% of patients in the placebo arm. “So, theoretically, this disbalance in histology may have caused a positive bias in favor of pembrolizumab,” Mirza said.

Also, as in other pembrolizumab trials, there did not seem to be activity in patients who were biomarker negative, and, in the KEYNOTE-826 trial, 11% of the population was biomarker negative, Mirza noted.

“My take home message would be that pembrolizumab plus chemotherapy with bevacizumab in a biomarker positive population shall be the new standard of care for women with persistent recurrent—or perhaps primary metastatic—cervical cancer,” Mirza concluded.

1. Adding pembrolizumab to standard platinum-based chemotherapy—with or without bevacizumab—significantly improved progression-free survival in women with metastatic cervical cancer, according to the latest results from KEYNOTE-826.

2. The researchers suggest that this could become the new standard of care for metastatic cervical cancer.

Peggy Peck, Editor-in-Chief, BreakingMED™

Cat ID: 120

Topic ID: 78,120,730,120,697,935,191,192,925,696