Clinical Trial

. 2024 Sep;13(18):e70236.

doi: 10.1002/cam4.70236.

Cemiplimab monotherapy in Japanese patients with recurrent or metastatic cervical cancer

Kosei Hasegawa¹, Shunji Takahashi², Kimio Ushijima³, Masao Okadome⁴, Kan Yonemori⁵, Harushige Yokota⁶, Ignace Vergote⁷, Bradley J Monk⁸, Krishnansu S Tewari⁹, Keiichi Fujiwara¹, Jingjin Li¹⁰, Shaheda Jamil¹⁰, Anne Paccaly¹⁰, Kazuhiro Takehara¹¹, Tomoka Usami¹², Yoichi Aoki^#¹³, Nao Suzuki¹⁴, Yoichi Kobayashi¹⁵, Yoshio Yoshida¹⁶, Hidemichi Watari¹⁷, Frank Seebach¹⁰, Israel Lowy¹⁰, Melissa Mathias¹⁰, Matthew G Fury¹⁰, Ana Oaknin¹⁸

Affiliations

¹ Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan.
² Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
³ Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan.
⁴ Gynecology Service, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
⁵ Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁶ Saitama Cancer Center, Saitama, Japan.
⁷ Department of Gynecology and Obstetrics, University Hospitals, Katholieke Universiteit Leuven, Leuven, Belgium.
⁸ Division of Gynecologic Oncology, University of Arizona and Creighton University, Phoenix, Arizona, USA.
⁹ Department of Gynecology and Obstetrics, University of California, Irvine, California, USA.
¹⁰ Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
¹¹ Department of Gynaecologic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
¹² Department of Obstetrics and Gynaecology, Ehime University School of Medicine, Toon, Japan.
¹³ Department of Obstetrics and Gynaecology, University of the Ryukyus Hospital, Okinawa, Japan.
¹⁴ Department of Obstetrics and Gynaecology, St Marianna University School of Medicine, Kawasaki, Japan.
¹⁵ Department of Obstetrics and Gynaecology, Faculty of Medicine, Kyorin University, Tokyo, Japan.
¹⁶ Department of Obstetrics and Gynaecology, University of Fukui, Fukui, Japan.
¹⁷ Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
¹⁸ Gynaecologic Cancer Programme, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.

^# Contributed equally.

PMID: 39325020
PMCID: PMC11426160
DOI: 10.1002/cam4.70236

Clinical Trial

Cemiplimab monotherapy in Japanese patients with recurrent or metastatic cervical cancer

Kosei Hasegawa et al. Cancer Med. 2024 Sep.

. 2024 Sep;13(18):e70236.

doi: 10.1002/cam4.70236.

Authors

Affiliations

¹ Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan.
² Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
³ Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan.
⁴ Gynecology Service, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
⁵ Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁶ Saitama Cancer Center, Saitama, Japan.
⁷ Department of Gynecology and Obstetrics, University Hospitals, Katholieke Universiteit Leuven, Leuven, Belgium.
⁸ Division of Gynecologic Oncology, University of Arizona and Creighton University, Phoenix, Arizona, USA.
⁹ Department of Gynecology and Obstetrics, University of California, Irvine, California, USA.
¹⁰ Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
¹¹ Department of Gynaecologic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
¹² Department of Obstetrics and Gynaecology, Ehime University School of Medicine, Toon, Japan.
¹³ Department of Obstetrics and Gynaecology, University of the Ryukyus Hospital, Okinawa, Japan.
¹⁴ Department of Obstetrics and Gynaecology, St Marianna University School of Medicine, Kawasaki, Japan.
¹⁵ Department of Obstetrics and Gynaecology, Faculty of Medicine, Kyorin University, Tokyo, Japan.
¹⁶ Department of Obstetrics and Gynaecology, University of Fukui, Fukui, Japan.
¹⁷ Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
¹⁸ Gynaecologic Cancer Programme, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.

^# Contributed equally.

PMID: 39325020
PMCID: PMC11426160
DOI: 10.1002/cam4.70236

Abstract

Background: In the phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first-line platinum-based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan.

Methods: Patients were enrolled regardless of programmed cell death-ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigator's choice single-agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression-free survival (PFS) and objective response rate (ORR).

Results: Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow-up was 13.6 (6.0-25.3) versus 18.2 (6.0-38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0-not evaluable) and 9.4 (5.4-14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43-1.68). Median PFS (95% CI) was 4.0 (1.4-8.2) versus 3.7 (1.8-4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50-1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44-13.99). Incidence of treatment-emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively.

Discussion: While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6-month shorter median duration of follow-up versus the overall study population.

Keywords: cemiplimab; cervical cancer; chemotherapy; immunotherapy; programmed cell death‐1.

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Conflict of interest statement

Kosei Hasegawa reports research grants from Merck Sharp & Dohme, Ono, Takeda, Daiichi‐Sankyo, and Eisai; honoraria from Takeda, Chugai Pharma, Kyowa‐Kirin, Genmab, AstraZeneca, and Merck Sharp & Dohme; and consulting/advisory board fees from Merck Sharp & Dohme, Eisai, and Takeda. Shunji Takahashi reports honoraria from Daiichi Sankyo, Eisai, Bayer, Taiho Pharmaceutical, Merck Sharp & Dohme, Novartis, Chugai Pharma, AstraZeneca, Bristol‐Myers Squibb Japan, Ono Pharmaceutical, Nihonkayaku, Pfizer, and Lilly Japan; an advisory role at Bayer; research funding from Daiichi Sankyo, Sanofi, Eisai, Bayer, Taiho Pharmaceutical, Merck Sharp & Dohme, Novartis, Chugai Pharma, AstraZeneca, Bristol‐Myers Squibb, Lilly, Ono Pharmaceutical, PharmaMar, and Pfizer/EMD Serono; and travel, accommodation, and expenses from Daiichi Sankyo and Novartis. Kimio Ushijima reports honoraria from Chugai Pharma; and research funding from Kaken Pharmaceutical, Takeda Pharmaceutical Company, and Tsumura & Co. Masao Okadome reports no conflict of interest. Kan Yonemori reports lecture fees and/or advisory fees from AstraZeneca, Chugai Pharma, Daiichi Sankyo, Esai, Ono Pharmaceutical, Novartis, Pfizer, and Takeda Pharmaceutical Company. Harushige Yokota reports honoraria from Chugai Pharma, Kaken Pharmaceutical, and Merck Sharp & Dohme; and research funding from Pfizer and Zeria Pharmaceutical. Ignace Vergote reports consulting fees from AstraZeneca, Elevar Therapeutics, Genmab, GlaxoSmithKline, Immunogen, Merck Sharp & Dohme, and Oncoinvent; and contracted research from Genmab and Hoffmann‐La Roche. Bradley J Monk reports consulting honoraria from Aravive, Asymmetric Therapeutics, Boston Biomedical, ChemoCare, ChemoID, Circulogene, Conjupro Biotherapeutics, Eisai, Geistlich, Genmab/Seattle Genetics, Gynecologic Oncology Group Foundation, ImmunoGen, Immunomedics, Incyte, Laekna Health Care, Mateon/Oxigene, Merck, Mersana, Myriad, Nucana, Oncomed, Oncoquest, Oncosec, Perthera, Pfizer, Precision Oncology, Puma, Regeneron, Samumed, Takeda, VBL, and Vigeo; and consulting/speaker honoraria from AstraZeneca, Clovis, Janssen/Johnson & Johnson, Roche/Genentech, and Tesaro/GSK. Krishnansu S Tewari reports honoraria from Tesaro and Clovis Oncology; consulting fees from Genentech, Tesaro, Clovis, and AstraZeneca; speaker fees from Genentech, AstraZeneca, Merck, Tesaro, and Clovis; research grants from AbbVie, Genentech, Morphotek, Merck, and Regeneron Pharmaceuticals, Inc; and travel/accommodation expenses from Genentech. Keiichi Fujiwara reports receiving consulting fees and/or grant support from Pfizer, Daiichi Sankyo, Eisai, Immunogen, Kyowa Hakko Kirin, Merck Sharp & Dohme, Mochida Pharmaceutical, NanoCarrier, Novartis, Oncotherapy, Regeneron Pharmaceuticals, Inc., Taiho, Zeria, Chugai Pharma, Genmab, and Takeda Pharmaceutical Company. Jingjin Li, Shaheda Jamil, Anne Paccaly, Frank Seebach, Israel Lowy, Melissa Mathias, and Matthew G Fury are employees and shareholders of Regeneron Pharmaceuticals, Inc. Kazuhiro Takehara reports lecture fees and consulting fees from Takeda. Tomoka Usami reports no conflict of interest. Yoichi Aoki reports no conflict of interest. Nao Suzuki reports no conflict of interest. Yoichi Kobayashi reports no conflict of interest. Yoshio Yoshida reports no conflict of interest. Hidemichi Watari reports honoraria from Merck Sharp & Dohme, Tsumura & Co, AstraZeneca, Aska Pharmaceutical Co, Ltd, Terumo, Bayer Yakuhin, Kaken Pharmaceutical, Mochida Pharmaceutical Co, Ltd, Daiichi Sankyo/UCB Japan, Chugai Pharmaceutical, and Takeda; consulting/advisory board fees from Decision Resources Group Japan, Kaken Pharmaceutical, and Chugai Pharmaceutical; and research grants from Hokkaido Welfare Federation of Agricultural Cooperatives, Kaken Pharmaceutical, Mochida Pharmaceutical Co, Ltd, Taiho Pharmaceutical, Chugai Pharmaceutical, Hokkaido Cancer Society, and Takeda. Ana Oaknin reports advisory board fees from Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro, Inmunogen, Genmab, Mersana Therapeutic, GlaxoSmithKline, and Deciphera Pharmaceuticals; and support for travel or accommodation from Roche, AstraZeneca, and PharmaMar.

Figures

**FIGURE 1**
Overall survival in (A) the Japanese subgroup and (B) the overall population. Data cutoff date: January 4, 2021. ^aStratified by histology (SCC vs. AC) according to IWRS. ^bFrom randomization to data cutoff date. ^cStratified by histology (SCC vs. AC) and geographic region (North America vs. Asia vs. ROW) according to IWRS. AC, adenocarcinoma or adenosquamous carcinoma; CI, confidence interval; HR, hazard ratio; IWRS, interactive web response system; OS, overall survival; ROW, rest of world; SCC, squamous cell carcinoma.

**FIGURE 2**
Progression‐free survival in (A) the Japanese subgroup and (B) the overall population. Data cutoff date: January 4, 2021. ^aStratified by histology (SCC vs. AC) according to IWRS. ^bStratified by histology (SCC vs. AC) and geographic region (North America vs. Asia vs. ROW) according to IWRS. AC, adenocarcinoma or adenosquamous carcinoma; CI, confidence interval; HR, hazard ratio; IWRS, interactive web response system; PFS, progression‐free survival; ROW, rest of world; SCC, squamous cell carcinoma.

**FIGURE 3**
Observed mean (SD) cemiplimab C _trough and C _max over time in the Japanese subgroup and the overall study population treated with cemiplimab 350 mg every 3 weeks. Data cutoff date: January 4, 2021. C _max, maximum concentration; C _trough, trough concentration at the end of the dosing interval; SD, standard deviation.

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References

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Cemiplimab monotherapy in Japanese patients with recurrent or metastatic cervical cancer

Affiliations

Cemiplimab monotherapy in Japanese patients with recurrent or metastatic cervical cancer

Authors

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Abstract

Conflict of interest statement

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