LBA38 - Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: A randomized, double-blind, phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study

Background

Pembrolizumab (pembro) has shown efficacy in patients (pts) with cervical cancer. The effect of chemoradiotherapy may be enhanced by immunotherapy. ENGOT-cx11/GOG-3047/KEYNOTE-A18(NCT04221945) assessed the efficacy and safety of pembro + concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer.

Methods

Eligible pts with newly diagnosed, previously untreated, high-risk locally advanced cervical cancer (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA) were randomized 1:1 to receive 5 cycles of pembro 200 mg or pbo Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. The CCRT regimen included 5 cycles (with optional 6th dose) of cisplatin 40 mg/m² Q1W + EBRT then brachytherapy. Pts were stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), stage at screening (stage IB2-IIB vs III-IVA) and planned total radiotherapy dose. Primary endpoints were PFS per RECIST version 1.1 by investigator and OS.

Results

1060 pts were randomized to pembro + CCRT (n=529) or pbo + CCRT (n=531). At the protocol-specified first interim analysis (January 9, 2023, data cutoff), median follow-up was 17.9 mo (range, 0.9-31.0). Pembro + CCRT showed a statistically significant improvement in PFS vs pbo + CCRT. 24-mo PFS was 67.8% with pembro + CCRT vs 57.3% with pbo + CCRT; median PFS was not reached in either group (HR=0.70 [95% CI, 0.55-0.89; P=0.0020]); results were consistent across all prespecified subgroups. With only 103 events (42.9% maturity), the addition of pembro to CCRT showed a favorable trend in OS (HR=0.73 [95% CI, 0.49-1.07]); these data have not crossed the boundary of statistical significance. Grade ≥3 TRAE incidence was 67.0% in the pembro + CCRT group and 60.0% in the pbo + CCRT group.

Conclusions

Pembro + CCRT showed a statistically significant and clinically meaningful improvement in PFS and a favorable trend in OS compared with pbo + CCRT in pts with high-risk locally advanced cervical cancer and had a manageable safety profile. These data suggest pembro + CCRT can be considered as a new standard of care for this population.

Clinical trial identification

NCT04221945.

Editorial acknowledgement

Editorial assistance in the writing of the abstract was provided by Christine McCrary Sisk, an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A.

Disclosure

D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis; Financial Interests, Personal, Advisory Board, Invited member of advisory board and invited speaker: Seagen, Immunogen, Genmab; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trials: MSD, Clovis Oncology, GSK, PharmaMar; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, Clovis Oncology, roche, Incyte; Non-Financial Interests, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non-Financial Interests, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Non-Financial Interests, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non-Financial Interests, Member, Board of Directors: GCIG; Other, Grants for traveling: AstraZeneca, Clovis Oncology, GSK. Y. Xiang: Financial Interests, Institutional, Funding, Study funding: MSD; Financial Interests, Personal, Advisory Role, Member of Scientific Advisory Committee for MK3475-A18 study: MSD. K. Hasegawa: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Takeda, Chugai, Genmab, Kaken, Eisai, Sanofi, GSK; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Funding, contracted research: MSD, Ono, Daiichi Sankyo, Eisai, Takeda. G. Scambia: Financial Interests, Personal, Invited Speaker, Speaker: Baxter Healthcare, GSK, Intuitive Surgical Inc., AstraZeneca & MSD, Olympus Europa, GSK, AstraZeneca & MSD, Olympus Europa; Financial Interests, Personal, Advisory Board, Trainer: Covidien AG (Medtronic company); Financial Interests, Institutional, Coordinating PI, ‘IsoMSLN’ in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic; Financial Interests, Institutional, Coordinating PI, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca; Financial Interests, Institutional, Coordinating PI, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib.: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, Phase 3, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.; Financial Interests, Institutional, Coordinating PI, Phase 2b randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG; Financial Interests, Institutional, Coordinating PI, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd; Financial Interests, Institutional, Coordinating PI, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial.: Merck. M.H. Leiva Galves: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Roche, MSD, BMS. P. Ramos Elias: Financial Interests, Personal, Invited Speaker, Guest speaker at educational events: MSD, Asofarma, Novartis, AstraZeneca; Financial Interests, Personal, Advisory Board, Participation as a local expert on advisory board meetings: Bristol Myers Squibb, Asofarma, AstraZeneca; Financial Interests, Personal, Advisory Board, local expert on advisory board meetings: Pfizer; Financial Interests, Personal and Institutional, Local PI, Fees for conducting clinical studies: MSD, Roche Genentech, Zymeworks. A. Acevedo: Financial Interests, Institutional, Principal Investigator: Merck Sharp & Dohme. J. Vizkeleti: Financial Interests, Institutional, Principal Investigator: Merck & Co., Inc.. A.J.P.D.S. Gomes: Financial Interests, Personal, Invited Speaker: Astellas, Bayer, Janssen, AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer, Janssen. F. Contreras Mejia: Financial Interests, Personal, Invited Speaker: MSD, BMS, GSK, Eli Lillly, AstraZeneca, Novartis; Financial Interests, Personal, Expert Testimony: MSD, Janssen, GSK, Eli Lilly, BMS; Financial Interests, Personal, Other, Meeting and travel support: MSD, Amgen. A. Reiss: Financial Interests, Personal, Advisory Board: MSD Israel. J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon; Financial Interests, Personal and Institutional, Local PI: Beigene; Financial Interests, Personal, Steering Committee Member: AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Institutional, Research Grant: ONO, Takeda. F. Zagouri: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Personal, Writing Engagement: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Institutional, Funding: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Personal, Principal Investigator: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Institutional, Principal Investigator: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead. K. Li: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. K. Ussui Yamada: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. S. Toker: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. S. Pignata: Financial Interests, Personal, Advisory Board: Roche, AZ, MSD, Clovis, GSK, PharmaMar; Financial Interests, Institutional, Funding: Roche, MSD, Pfizer, AZ. L.R. Duska: Financial Interests, Personal, Advisory Board, Scientific advisory board: Aadi Bioscience; Financial Interests, Personal, Royalties, I write expert content for UpToDate: UpToDate; Financial Interests, Personal, Other, I serve on the Editorial Board: British Journal of Obstetrics and Gynecology; Financial Interests, Institutional, Research Grant, Merck has provided funding for investigator initiated trials to my institution: Merck; Non-Financial Interests, Advisory Role, Acted as an expert advisor for: Merck. All other authors have declared no conflicts of interest.