PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer

Danny Rischin, Marta Gil-Martin, Antonio González-Martin, Irene Braña, June Y. Hou, Daniel Cho, Gerald S. Falchook, Silvia Formenti, Salma Jabbour, Kathleen Moore, Aung Naing, Kyriakos P. Papadopoulos, Joaquina Baranda, Wen Fury, Minjie Feng, Elizabeth Stankevich, Jingjin Li, N. Alice Yama-Dang, Suk Young Yoo, Israel LowyMelissa Mathias, Matthew G. Fury

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Objectives: To characterize the safety, tolerability, and anti-tumor activity of cemiplimab as monotherapy or in combination with hypofractionated radiation therapy (hfRT) in patients with recurrent or metastatic cervical cancer. To determine the association between histology and programmed death-ligand 1 (PD-L1) expression. Methods: In non-randomized phase I expansion cohorts, patients (squamous or non-squamous histology) received cemiplimab 3 mg/kg intravenously every 2 weeks for 48 weeks, either alone (monotherapy cohort) or with hfRT during week 2 (combination cohort). Due to insufficient tissue material, PD-L1 protein expression was evaluated in commercially purchased samples and mRNA expression levels were analyzed from The Cancer Genome Atlas (TCGA). Results: Twenty patients enrolled in both cohorts in total; 10 had squamous histology. The most common adverse events of any grade were diarrhea, fatigue, and hypokalemia, occurring in 35%, 25%, and 25%, respectively. Objective response rate was 10% in each cohort; responders had squamous histology. Duration of response was 11.2 months and 6.4 months for the responder in the monotherapy and combination cohort, respectively. Irradiated lesions were not included in the response assessments. In separate archived specimens (N = 155), PD-L1 protein expression in tumor and immune cells was negative (<1%) more commonly in adenocarcinoma than in squamous tumors. PD-L1 mRNA levels were lower in adenocarcinoma than squamous cell tumors (1.2 vs 5.0 mean transcripts per million, respectively) in TCGA. Conclusions: Cemiplimab has activity in cervical squamous cell carcinoma. The phase I results, combined with results from other anti–PD-1 trials in cervical cancer and our biomarker analyses have informed the design of the ongoing phase III trial, with the primary overall survival hierarchical analyses being done first in patients with squamous histology.

Original languageEnglish (US)
Pages (from-to)322-328
Number of pages7
JournalGynecologic Oncology
Volume159
Issue number2
DOIs
StatePublished - Nov 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Obstetrics and Gynecology
  • Oncology

Keywords

  • Anti-PD-1
  • Cemiplimab
  • Metastatic cervical cancer
  • Recurrent cervical cancer

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