TY - JOUR
T1 - PD-1 blockade in recurrent or metastatic cervical cancer
T2 - Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer
AU - Rischin, Danny
AU - Gil-Martin, Marta
AU - González-Martin, Antonio
AU - Braña, Irene
AU - Hou, June Y.
AU - Cho, Daniel
AU - Falchook, Gerald S.
AU - Formenti, Silvia
AU - Jabbour, Salma
AU - Moore, Kathleen
AU - Naing, Aung
AU - Papadopoulos, Kyriakos P.
AU - Baranda, Joaquina
AU - Fury, Wen
AU - Feng, Minjie
AU - Stankevich, Elizabeth
AU - Li, Jingjin
AU - Yama-Dang, N. Alice
AU - Yoo, Suk Young
AU - Lowy, Israel
AU - Mathias, Melissa
AU - Fury, Matthew G.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Anti-PD-1
KW - Cemiplimab
KW - Metastatic cervical cancer
KW - Recurrent cervical cancer
UR - http://www.scopus.com/inward/record.url?scp=85090478334&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85090478334&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2020.08.026
DO - 10.1016/j.ygyno.2020.08.026
M3 - Article
C2 - 32917410
AN - SCOPUS:85090478334
SN - 0090-8258
VL - 159
SP - 322
EP - 328
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 2
ER -