Mansoor Raza Mirza, MD
The invited discussant of EMPOWER-Cervical 1 was Mansoor Raza Mirza, MD, Chief Oncologist at Copenhagen University Hospital and Chairman of the European Network of Gynaecological Oncology Trials group (ENGOT). Dr. Mirza called the findings “amazing” and predicted they will “usher in a new era” in the treatment of cervical cancer.
As he pointed out, concurrent chemoradiation has resulted in significant improvements in survival, yet for patients with recurrent or metastatic disease, overall survival remains quite short. In GOG 240, the addition of bevacizumab to platinum-doublet chemotherapy improved median survival to 17 months,1 but after further disease progression, there is no standard of care for second-line treatment, and survival becomes “quite pathetic…. Now we are seeing the next phase III data that are changing practice again,” he commented.
Dr. Mirza explained there is a strong rationale for treating cervical cancer with immunotherapy, and, to this end, a variety of immunotherapeutic approaches are being evaluated. Pembrolizumab is already approved under the accelerated approval program of the FDA in patients with PD-L1-expressing tumors; nivolumab plus ipilimumab has shown synergy in small trials; and a newer PD-1 antibody, balstilimab, is moving to phase III trials alone and in combination with the anti–CTLA-4 agent zalifrelimab.
‘Impressive’ Overall Survival
Commenting on EMPOWER-Cervical 1, Dr. Mirza praised the “clean and simple design,” the relevant endpoint of overall survival, and the relevant stratification factors. “The result is an impressive overall survival benefit,” he commented. “The median increased from 8.5 months to 12.0 months, but I think it’s more important to look at the tail of the curve. This is efficacy that is extended, and these curves are not falling into each other. The beauty of immunotherapy is that responders have long-term benefit.”
Dr. Mirza emphasized that the study dispels the belief that only tumors with squamous cell histology respond to immunotherapy, since patients with adenocarcinoma also had an improvement in survival with second-line cemiplimab. Although this is a positive trial, he added, it also reveals an unmet need: more than half the patients experienced disease progression within 3 months of starting treatment. “Who are these patients, and how can their outcomes be improved?” he asked.
Dr. Mirza said he awaits data according to PD-L1 status and would like to see details of prior and subsequent treatments, which may have affected outcomes. Finally, he said, “I think we should move cemiplimab into earlier lines of treatment, where we will probably have even better results than we see here.”
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 European Network of Gynaecological Oncology Trials, European Society for Gynaecological Oncology, and Gynecological Cancer InterGroup.
1. Tewari KS, Sill MW, Long HJ, et al: Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 370:734-743, 2014.
The PD-L1 inhibitor cemiplimab-rwlc has become the first immunotherapy to yield a statistically significant and clinically meaningful survival benefit in recurrent or metastatic cervical cancer progressing after first-line platinum-containing chemotherapy. Patients were enrolled irrespective of...