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BACKGROUND Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)--blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population. METHODS In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status. Women were randomly assigned (1:1) to receive cemiplimab (350 mg every 3 weeks) or the investigator's choice of single-agent chemotherapy. The primary end point was overall survival. Progression-free survival and safety were also assessed. RESULTS A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was longer in the cemiplimab group than in the chemotherapy group (12.0 months vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.84; two-sided P<0.001). The overall survival benefit was consistent in both histologic subgroups (squamous-cell carcinoma and adenocarcinoma [including adenosquamous carcinoma]). Progression-free survival was also longer in the cemiplimab group than in the chemotherapy group in the overall population (hazard ratio for disease progression or death, 0.75; 95% CI, 0.63 to 0.89; two-sided P<0.001). In the overall population, an objective response occurred in 16.4% (95% CI, 12.5 to 21.1) of the patients in the cemiplimab group, as compared with 6.3% (95% CI, 3.8 to 9.6) in the chemotherapy group. An objective response occurred in 18% (95% CI, 11 to 28) of the cemiplimab-treated patients with PD-L1 expression greater than or equal to 1% and in 11% (95% CI, 4 to 25) of those with PD-L1 expression of less than 1%. Overall, grade 3 or higher adverse events occurred in 45.0% of the patients who received cemiplimab and in 53.4% of those who received chemotherapy. CONCLUSIONS Survival was significantly longer with cemiplimab than with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. (Funded by Regeneron Pharmaceuticals and Sanofi; EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 ClinicalTrials.gov number, NCT03257267. [ABSTRACT FROM AUTHOR]

Aim: Cemiplimab has demonstrated significantly longer survival than physician's choice of chemotherapy in patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. We report the final survival analysis from the phase III randomized study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9)., Methods: Cemiplimab (n = 304) or chemotherapy (n = 304) were administered every 3 weeks. The primary endpoint was overall survival (OS). Patients were included regardless of programmed cell death-ligand 1 (PD-L1) status., Results: At a median follow-up of 47.3 months (data cut-off: April 20, 2023), median OS was 11.7 versus 8.5 months for patients treated with cemiplimab and chemotherapy, respectively (hazard ratio 0.67, 95 % confidence interval 0.56-0.80, p < .00001). OS benefit was seen in PD-L1 positive and negative populations, even though more patients with PD-L1 < 1 % (n = 92), had poor performance status in the cemiplimab arm than the chemotherapy arm (61.4 % vs 47.9 %)., Conclusion: This final analysis confirms that cemiplimab maintains survival benefit compared with chemotherapy in recurrent cervical cancer after progression on first-line platinum therapy, regardless of PD-L1 expression. The safety profile was consistent with published data; incidences of adverse events were similar between cemiplimab and chemotherapy groups. These results support the use of second-line cemiplimab for patients with recurrent cervical cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ana Oaknin: Personal fees for advisory boards: AstraZeneca, Clovis Oncology, Deciphera, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, MSD, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Shattuck Labs, iTeos, Eisai; travel and accommodation: AstraZeneca, PharmaMar, Roche; funding to institution: AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc., Eisai Ltd, F. Hoffmann-La Roche Ltd, Regeneron Pharmaceuticals, Inc., ImmunoGen Inc, MSD de España SA, Takeda, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb. Bradley J. Monk: Consulting fees: Acrivon, Adaptimune, Agenus, Akeso Bi, Amgen, Aravive, AstraZeneca, Bayer, Clovis Oncology, Eisai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna, Macrogenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron Pharmaceuticals, Inc., Roche/Genentech, Sorrento, TESARO/GSK, US Oncology Research, VBL, Verastem, Zentalis; payment/honoraria: AstraZeneca, Eisai, Myriad Roche/Genentech, TESARO/GSK. Andreia Cristina de Melo: Funding to institution: Amgen, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, GSK, MSD, Novartis, Regeneron Pharmaceuticals, Inc., Roche; personal fees for lectures, presentations, speaker bureaus, manuscript writing, or educational events, and personal fees for participation in a data safety monitoring board or advisory board: AstraZeneca, Bristol Myers Squibb, Daiichi, GSK, MSD, Novartis, Roche. Hee Seung Kim: Nothing to disclose. Yong Man Kim: Stock and other ownership interests: Genolution, Johnson & Johnson; research funding: Regeneron Pharmaceuticals, Inc., Roche. Alla S. Lisyanskaya: Nothing to disclose. Vanessa Samouëlian: Conferences: AstraZeneca, Eisai, GSK, Merck; advisory board: AstraZeneca, GSK, Merck. Domenica Lorusso: Funding: AstraZeneca, Clovis Oncology, Pharma&, Genmad, GSK, Immunogen, MSD, Pharmamar, Novartis, Seagen, Alkermes, Incyte, Roche, Corcept; consulting fees: AstraZeneca, Corcept, Clovis Oncology, Daiichi Sankyo, Genmad, GSK, Immunogen, MSD, Novartis, Oncoinvest, Novocure, Seagen, Sutro; honoraria: AstraZeneca, Corcept, Genmab, GSK, Immunogen, MSD, Seagen; advisory boards: AstraZeneca, Corcept, Clovis Oncology, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Oncoinvest, Novocure, Seagen, Sutro. Fernanda Damian: Nothing to disclose. Chih-Long Chang: Payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events: AstraZeneca and MSD. Evgeniy Gotovkin: advisory/consultancy honoraria: AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar, Roche; speaker bureau/expert testimony honoraria: AstraZeneca-MSD, PharmaMar, Roche, GSK-Tesaro, Clovis, Eisai; and travel/accommodation/expenses from Roche, GSK-Tesaro, Baxter. Shunji Takahashi: Honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events: AstraZeneca, Bayer, Bristol Myers Squib, Chugai, Daichi−Sankyo, Eisai, MSD, Novartis, Ono Pharmaceutical, Taiho; institutional grants: AstraZeneca, Bayer, Bristol Myers Squib, Chugai, Daichi−Sankyo, Eisai, MSD, Novartis, Ono Pharmaceutical, Taiho; institutional grant/honoraria: Sanofi. Daniella Ramone: Medical Director at ICON plc. Beata Maćkowiak-Matejczyk: Honoraria for lectures: AstraZeneca, GSK; support for attending meetings and/or travel: AstraZeneca; advisory board roles: GSK, Seagen. Laura Polastro: Grant research: Eisai, GSK, Seagen, Pharmamar and Pfizer. Maria Jesús Rubio Pérez: Consulting or advisory role: AstraZeneca, Clovis, Eisai, GSK, MSD, PharmaMar, Roche; speaker bureau: AstraZeneca, Clovis, GSK, Roche, MSD, Pharmamar; travel/accommodation/expenses: AstraZeneca, MSD, PharmaMar, Roche. Eva Maria Guerra Alia: Advisory/consultancy honoraria: AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar, Roche; speaker bureau/expert testimony honoraria: AstraZeneca-MSD, PharmaMar, Roche, GSK-Tesaro, Clovis, Eisai; travel/accommodation/expenses: Roche, GSK-Tesaro, Baxter. Nicoletta Colombo: Consulting (personal) fees: AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Inc., Mersana, MSD Oncology, Novocure, Pieris, Pfizer, Roche/Genentech; personal fees, lectures, presentations, speaker bureaus, manuscript writing, or educational events: AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Inc., MSD Oncology, Novartis, Roche/Genentech; participation in a data safety monitoring board or advisory board: AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Inc., Mersana, MSD Oncology, Novocure, Roche/Genentech, Pfizer; immediate family member is an employee of Sarepta. Yulia Makarova: Nothing to disclose. Jeffrey C Goh: Consultant/advisory board member: MSD, AstraZeneca, BMS, GSK; speaker bureaus for: MSD, AstraZeneca, BMS, Ipsen, GSK, Janssen & Bayer; travel/accommodation expenses: Bayer. Kosei Hasegawa: Consulting or advisory role: Eisai, Merck KGaA, MSD, Sanofi, Takeda, Roche, Daiichi Sankyo, Genmab, GSK; honoraria: AstraZeneca, Chugai Pharma, Eisai, Genmab, MSD, Kyowa Kirin, Daiichi Sankyo, Sanofi, Takeda; research grants: Daiichi Sankyo, Eisai, MSD, Ono Pharmaceutical, Takeda; travel expenses: Regeneron Pharmaceuticals, Inc., Seagen. Paulo Mora: Payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events: AstraZeneca, MSD; support for attending meetings and/or travel: AstraZeneca; participation in a data safety monitoring board or advisory board: Knight. Joanna Pikiel: Grants or contracts: Astra Zeneca, GSK, Labcorp Drug Development, MSD, Roche, Sichuan Kelun-Biotech Biopharmaceutical; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events: AstraZeneca, Elly Lily; support for attending meetings and/or travel: Elly Lily, Novartis. Ratnesh Srivastav: Nothing to disclose. Danny Rischin: Institutional research grant and funding: ALX Oncology, Bristol-Myers Squibb, GlaxoSmithKline, Kura Oncology, Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Roche, Sanofi; uncompensated scientific committee and advisory board roles: Eisai, Bicara, GlaxoSmithKline, Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi. Javier Perez, Suk Young Yoo, Bo Gao, Shaheda Jamil, Frank Seebach, Israel Lowy, Melissa Mathias, and Matthew G. Fury: employees and stockholders of Regeneron Pharmaceuticals, Inc. Krishnansu S. Tewari: financial relationships: AbbVie, AstraZeneca, Eisai, GSK, ImmunoGen, Karyopharm, Merck, Morphotek, Regeneron Pharmaceuticals, Inc., Roche/Genentech, Seagen/Genmab., (Copyright © 2025. Published by Elsevier Ltd.)

Mismatch repair-deficient (dMMR) endometrial cancer (EC) is an inflamed phenotype with poor outcomes when meeting high-risk criteria and limited treatment options in the adjuvant setting. We report protocol-prespecified subgroup analysis of patients with dMMR tumors from the phase III ENGOT-en11/GOG-3053/KEYNOTE-B21 study (ClinicalTrials.gov identifier: NCT04634877) in newly diagnosed, high-risk EC after surgery with curative intent. Patients were randomly assigned to pembrolizumab 200 mg or placebo (six cycles) plus carboplatin-paclitaxel (four to six cycles) once every 3 weeks, then pembrolizumab 400 mg or placebo once every 6 weeks (six cycles), respectively. MMR status was a stratification factor. Patients received radiotherapy at investigator discretion. Investigator-assessed disease-free survival (DFS) was a primary end point. No formal hypothesis testing was performed for subgroup analysis. In the intention-to-treat population, 141 patients in the pembrolizumab arm and 140 in the placebo arm had dMMR tumors. At this interim analysis, hazard ratio for DFS favored pembrolizumab (0.31 [95% CI, 0.14 to 0.69]); median DFS was not reached in either group. Two-year DFS rates were 92.4% (95% CI, 84.4 to 96.4) and 80.2% (95% CI, 70.8 to 86.9), respectively. No new safety signals occurred. Longer-term follow-up of outcomes will be evaluated at final analysis. Preplanned subgroup analysis on the basis of the study's stratification factors suggests that pembrolizumab plus chemotherapy improves DFS and is clinically relevant for patients with dMMR tumors in the curative-intent setting.