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Phase 3 Data Solidify Cemiplimab’s Role in Second-Line Treatment of Cervical Cancer


In May, results showed that cemiplimab (Libtayo, Regeneron/Sanofi) produced significant benefits: a 31% reduction in the risk of death and a 25% reduction in the risk of disease progression.

In 2018, presenters at the American Society of Clinical Oncology (ASCO) turned heads with word they were moving straight to a phase 3 trial in cervical cancer with the checkpoint inhibitor cemiplimab, based on responses from 2 of 3 patients in a phase 1 dose escalation trial.1

Results from just 3 patients led the largest trial ever of patients with an unmet need in cervical cancer: those with recurrent or metastatic disease who had already been treated with platinum-based chemotherapy. The investigators, led by Krishnansu S. Tewari, MD, professor and director of the Division of Gynecologic Oncology at the University of California, Irvine, launched GOG 3016, a study by the Gynecologic Oncology Group, a nonprofit funded by the National Cancer Institute.

Now called EMPOWER-1, the trial reported interim results in a May 2021 virtual plenary session of the European Society of Medical Oncology (ESMO), and Tewari followed with a presentation at the 2021 ESMO Virtual Congress September 16-21.2

The May results showed that cemiplimab (Libtayo, Regeneron/Sanofi) produced significant benefits: a 31% reduction in the risk of death (overall survival [OS]) and a 25% reduction in the risk of disease progression (progression-free survival [PFS]). At the ESMO session September 17, Tewari elaborated on those results and discussed their importance within the context of what women with advanced cervical cancer faced just a few years ago.

Tewari was part of the last big breakthrough in cervical cancer, when in 2013 he was the lead author of a GOG study that showed adding bevacizumab to chemotherapy could improve OS in advanced cervical cancer by 21%.3 But, “after that we had a bit of a drought,” he said. Commentator Rosalind Glasspool, MBBS, PhD, of the University of Glasgow, who appeared before Tewari, agreed.

The phase 3 results compared 304 patients taking cemiplimab with 304 taking the investigator’s choice of chemotherapy in patients in the second-line setting, regardless of PD-L1 expression. Patients received either 350 mg of cemiplimab intravenously every 3 weeks or chemotherapy for up to 96 weeks. Results showed the following:2

  • Median patient age was 51 years (range, 22-87); 477 patients had squamous cell carcinoma (SCC) and 131 had adenocarcinoma (AC).
  • Median cemiplimab exposure was 15 weeks.
  • Overall, the median OS was 12 months in the cemiplimab group and 8.5 months in the chemotherapy group, for an HR of 0.69 (0.56-0.84; P < .001).
  • In the SCC group, median OS was 11.1 months for cemiplimab vs 8.8 months for chemotherapy, for an HR of 0.73 (0.58-0.91; P = .003). In the AC group, the median OS was 13.3 months for cemiplimab vs 7.0 months for chemotherapy, for an HR of 0.56 (0.36-0.85, P < .005).
  • While patients received benefits regardless of PD-L1 status, Tewari’s presentation showed that the benefit compared with chemotherapy was higher among with PD-L1 of 1% or greater.
  • Quality-of-life scores for patients taking cemiplimab were maintained or slightly improved from baseline, while scores declined for those on chemotherapy.

Tewari said EMPOWER-1 stands out for its size and the nature of the patient population, and there were no new safety signals. “We feel this is a drug that can be used in the second-line setting for patients,” he said. The arrival of bevacizumab originally met an unmet need, “but it created a new group of patients that also had an unmet need. And that's patients who need a second-line therapy.”

Glasspool had discussed several emerging issues with the use of immunotherapy in advanced cervical cancer, including the possibilities for combination therapy—particularly anti-TIGIT treatment. Tewari said these are all interesting options, but it is important to remember how rapidly the field has moved.

“When Regeneron/Sanofi started the EMPOWER trial studying single agent PD-1 inhibitor with cemiplimab vs physician’s choice chemotherapy, there was nothing else really being done,” he said.

“Now the space is so crowded, and I think as we get more and more of the molecular data from these studies, and [can] better characterize who are going to be the exceptional responders to various therapies—and who are going to be the poor responders, we're going to be able to figure out where to plug in all these different agents. Because I think there's space for all of them.”


  1. Tewari KS, Vergote I, Oaknin A, et al. GOG 3016/ENGOT-cx9: an open-label, multi-national, randomized, phase 3 trial of cemiplimab, an anti-PD-1, versus investigator’s choice (IC) chemotherapy in ≥2 line recurrent or metastatic cervical cancer. J Clin Oncol 2018;36 (suppl; abstr TPS5600).
  2. Tewari KS, Monk BJ, Vergote I, et al. EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9: Interim analysis of phase III trial of cemiplimab vs investigator’s choice (IC) chemotherapy (chemo) in recurrent/metastatic (R/M) cervical carcinoma. Presented at the European Society of Medical Oncology 2021 Virtual Congress. September 16-21, 2021. Abstract VP4_2021.
  3. Tewari KS, Sill MW, Long HJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014;370:734-743. doi:10.1056/NEJMoa1309748
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