23O - A randomized, phase III, double-blind study of chemoradiotherapy with or without pembrolizumab in patients with high-risk, locally advanced, cervical cancer (KEYNOTE-A18/ENGOT-cx11/GOG-3047): Results for patients enrolled in Asia

Background

In the global, randomized, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945) study, pembrolizumab (pembro) + concurrent chemoradiotherapy (CCRT) showed a statistically significant improvement over placebo (pbo) + CCRT in PFS (median PFS, not reached in either group; hazard ratio [HR], 0.70 [95% CI, 0.55–0.89]; P=0.0020) and a favorable trend for improved OS vs pbo + CCRT (median OS not reached in either group; HR, 0.73 [95% CI, 0.49–1.07]) in patients with high-risk locally advanced cervical cancer (LACC) at the first interim analysis. We present results for patients enrolled in East Asia.

Methods

Eligible patients had newly diagnosed, previously untreated, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of lymph node status). Patients were randomly assigned (1:1) to receive 5 cycles of pembro 200 mg or pbo Q3W + CCRT, followed by 15 cycles of pembro 400 mg or pbo Q6W. CCRT included 5 cycles (with optional 6th dose) of cisplatin 40 mg/m² QW + external beam radiotherapy, then brachytherapy. Primary endpoints were PFS per RECIST v1.1 by investigator assessment and OS. No alpha was allocated to this exploratory analysis in the East Asia subgroup.

Results

299 patients were enrolled in East Asia (China, n=149; Japan, n=90; Republic of Korea, n=26; Thailand, n=20; Taiwan, n=14): pembro + CCRT, n=153; pbo + CCRT, n=146. Median follow-up at database cutoff (Jan 9, 2023) was 19.3 (range, 0.9–31.0) months. Median PFS was not reached in either treatment group (HR, 0.55 [95% CI, 0.35–0.88]); 24-month PFS rate was 77.6% in the pembro + CCRT group and 59.8% in the pbo + CCRT group. Grade ≥3 treatment-related AEs occurred in 78.3% of patients in the pembro + CCRT group and 77.4% in the pbo + CCRT group; none were grade 5. Immune-mediated AEs occurred in 43.4% and 10.3% of patients, respectively.

Conclusions

Consistent with the global analysis, pembro + CCRT demonstrated PFS benefit vs pbo + CCRT, with manageable safety in patients with high-risk LACC enrolled in East Asia. These results suggest pembro + CCRT may be considered as a new treatment option for patients with high-risk LACC in East Asia.

Clinical trial identification

NCT04221945; EudraCT 2019-003152-37.

Editorial acknowledgment

Writing support was provided by Christabel Wilson, MSc, of ICON plc (Blue Bell, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

Y. Xiang: Financial Interests, Personal, Research Grant: MSD. K. Hasegawa: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Takeda, Chugai, Genmab, Kaken, Eisai, Sanofi, GSK; Financial Interests, Personal, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Funding, contracted research: MSD, Ono, Daiichi Sankyo, Eisai, Takeda. H. Zhu: Financial Interests, Personal, Other, Honoraria: MSD. J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche, AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Financial Interests, Institutional, Invited Speaker: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon; Financial Interests, Personal and Institutional, Invited Speaker: BeiGene; Financial Interests, Institutional, Research Grant: ONO, Takeda. S. Suzuki: Financial Interests, Personal, Other, Honoraria: Eisai and MSD K.K. A. Lertkhachonsuk: Financial Interests, Personal, Invited Speaker, Honoraria: MSD, AstraZeneca and Eisai. K. Li, K.U. Yamada, S. Toker: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. 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, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clinical 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, Personal, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Personal, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, Clovis Oncology, Roche, Incyte; Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non-Financial Interests, Personal, Member, Board of Directors: GCIG; Other, Personal, Other, Grants for traveling: AstraZeneca, Clovis Oncology, GSK. All other authors have declared no conflicts of interest.