“The standard of care [in advanced cervical cancer] has been the addition of bevacizumab to platinum-based chemotherapy since 2014. Even with the addition of bevacizumab, we still need to do better. There is a substantial unmet need for new therapies,” said invited discussant Mansoor Raza Mirza, MD, of the Rigshospitalet, Copenhagen University, Denmark, after the presentation of results from KEYNOTE-826.
“The study today is a confirmatory trial for pembrolizumab in this setting. The stratification factors [metastatic or recurrent disease; biomarker status; and use of bevacizumab] are important. Many patients cannot tolerate bevacizumab, so there is a population in this study who got chemotherapy without bevacizumab,” he said.
“The strengths of the study are that it is phase III with a large sample size that allows for subgroup analysis. The endpoints are clinically meaningful. Both squamous cell carcinoma and adenocarcinoma are included. And, the quality of life shows a positive outcome in the experimental arm,” Dr. Mirza continued.
“At this preplanned interim analysis, median follow-up is already 22 months, and about two-thirds of the pembrolizumab group and 82.5% of the placebo group have discontinued treatment. A total of 50% of estimated deaths have occurred. The data are solid, and I don’t believe results will change with longer follow-up,” he noted.
Mansoor Raza Mirza, MD
Unanswered Questions
“Subgroup analyses are interesting in this trial. There was no effect of pembrolizumab in the biomarker-negative population [11% of the study population]. And, there was a lack of efficacy in patients with primary metastatic disease who were treatment-naive. The interpretation could be that treatment-naive patients have a greater response to platinum-based therapy, but the trial was not powered to answer that question. This is a subject for future study,” he said.
“Although the trial was not powered to answer the question of whether bevacizumab is needed, the hazard ratio was not significant in the one-third of patients who did not receive bevacizumab. This suggests that antiangiogenesis is needed. This is another question for future study,” Dr. Mirza continued. “The study also raises questions for the future, as to whether pembrolizumab plus chemotherapy is effective in primary metastatic disease, in the biomarker-negative population, in adenocarcinoma, and given without bevacizumab.”
Dr. Mirza concluded: “These results are groundbreaking. In the biomarker-positive population, pembrolizumab added to chemotherapy should be a new standard of care, perhaps for primary metastatic cervical cancer.”
DISCLOSURE: Dr. Mirza has served in a leadership role for Karyopharm Therapeutics and Sera Prognostics; holds stock or other ownership interests in Karyopharm Therapeutics and Sera Prognostics; has received honoraria from AstraZeneca, Geneos, Genmab/Seattle Genetics, GSK, Merck, Mersana, Oncology Venture, Roche, Sotio, Takeda, and Zai Lab; has served as a consultant or advisor to AstraZeneca, Biocad, Cerulean Pharma, Genmab, GSK, Karyopharm Therapeutics, Pfizer, and Sotio; has received institutional research funding from AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Pfizer, and Tesaro; holds institutional intellectual property in AstraZeneca, GSK, Pfizer, and Ultimovacs; has been reimbursed for travel, accommodations, or other expenses by AstraZeneca, Karyopharm Therapeutics, Pfizer, Roche, SeraCare, and Tesaro; and has held other relationships with the European Network of Gynaecological Oncology Trials, the European Society for Gynaecological Oncology, and the Gynecological Cancer InterGroup.
