Abstract 546P
Background
Pembrolizumab (pembro) previously demonstrated robust and durable antitumor activity in patients with MSI-H/dMMR advanced endometrial cancer in the open-label, multicohort, phase 2 KEYNOTE-158 study (NCT02628067). Here we report updated efficacy and safety outcomes with a substantially longer follow-up in the patients enrolled.
Methods
This analysis included those patients with previously treated, MSI-H/dMMR advanced endometrial cancer enrolled in cohorts D (advanced endometrial cancer of any MSI/MMR status) and K (any MSI-H/dMMR advanced solid tumor, except colorectal) of KEYNOTE-158. MSI-H/dMMR status was determined retrospectively by PCR at a central lab in cohort D and prospectively by PCR and/or IHC at a local lab in cohort K. Patients received pembro 200 mg Q3W for up to 35 cycles. Primary endpoint was ORR per RECIST v1.1 by independent central radiologic review. Secondary endpoints included DOR, PFS, OS, and safety.
Results
94 patients with previously treated MSI-H/dMMR advanced endometrial cancer were included in this analysis. Median time from first dose to data cutoff (Jan 12, 2022) was 54.5 (range, 14.7–71.4) mo. Efficacy results are shown in the Table. ORR was 50% (95% CI, 39.5%–60.5%); responses were seen across all prior treatment lines. 4-y DOR rate was 66% by K-M estimate. Median (95% CI) PFS and OS were 13.1 (4.3‒25.7) mo and 65.4 (29.5‒NR) mo; 4-y PFS and OS rates were 37% and 59%, respectively. Treatment-related AEs occurred in 71 patients (76%); 13 patients (14%) had grade 3‒4 treatment-related AEs (no grade 5). Table: 546P
| Analysis population (n = 94) | |
| ORR, % (95% CI) | 50 (39.5–60.5) |
| CR, n (%) | 15 (16) |
| PR, n (%) | 32 (34) |
| SD, n (%) | 17 (18) |
| ORR by prior treatment line, % (95% CI)a | |
| Neo-adjuvant and/or adjuvant therapy only (n = 10) | 40 (12.2–73.8) |
| 1 line (n = 39) | 59 (42.1–74.4) |
| >1 line (n = 45) | 44 (29.6–60.0) |
| DOR, median (range),b mo | 63.2 (2.9–63.2) |
| DOR ≥1 y,b % | 87 |
| DOR ≥2 y,b % | 71 |
| DOR ≥3 y,b % | 66 |
| DOR ≥4 y,b % | 66 |
| Median PFS (95% CI),b mo | 13.1 (4.3–25.7) |
| 4-y PFS rate,b % | 37 |
| Median OS (95% CI),b mo | 65.4 (29.5–NR) |
| 4-y OS rate,b % | 59 |
K-M, Kaplan-Meier; NR, not reached. aPercentages are based on number of patients in each subgroup. bK-M estimate
Conclusions
These updated results reconfirm the robust and durable antitumor activity of pembro and show encouraging survival outcomes in patients with advanced endometrial carcinoma that is MSI-H/dMMR, who have PD following prior systemic therapy and are not candidates for curative surgery or radiation, supporting the use of pembro in this setting.
Clinical trial identification
NCT02628067.
Editorial acknowledgement
Medical 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
D. O'Malley: Financial Interests, Personal, Advisory Board: AstraZeneca, Tesaro/GSK, BBI, Immunogen, Ambry, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, GOGFoundation, Iovance Biotherapeutics, Inc, Myriad Genetics, Eisai, Agenus, Tarveda, Merck & Co., Inc., Rahway, NJ, USA, SeaGen, Novartis, ; Financial Interests, Institutional, Research Grant: AstraZeneca, Tesaro/GSK, ImmunoGen, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc, Cerulean Pharma, GOGFoundation, NCI, Bristol Mye. G.M. Bariani: Financial Interests, Personal, Research Grant: Mabxience; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Libbs. P.A. Cassier: Financial Interests, Personal, Advisory Board: Merck Serono/EMD, Roche, Amgen; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Advisor: OSE immunotherapeutics; Financial Interests, Institutional, Invited Speaker: Abbvie, Amgen, Blueprint, Exelixis, GSK, Janssen, Novartis, Roche, Taiho, LOXO/Eli Lilly; Non-Financial Interests, Institutional, Product Samples: plexxikon, Novartis, MSD, AstraZeneca, GSK. A. Marabelle: Financial Interests, Institutional, Funding, funding to institution during the conduct of the study: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD); Financial Interests, Personal, Other, honorarium: MSD; Financial Interests, Personal, Research Grant: Fondation MSD Avenir and Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb and MSD. A.R. Hansen: Financial Interests, Personal, Advisory Board: Genentech/Roche, Merck & Co., GSK, Bristol Myers Squibb, Novartis, Boehringer Ingelheim, AstraZeneca, MedImmune; Financial Interests, Personal, Research Grant: Genentech/Roche, Merck & Co., GSK, Bristol Myers Squibb, Novartis, Boehringer Ingelheim, AstraZeneca, MedImmune; Financial Interests, Personal, Research Grant, research funding outside the submitted work: Boston Medical. A. De Jesus-Acosta: Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Advisory Board: Merck & Co., Inc., Rahway, NJ, USA. W.H. Miller: Financial Interests, Personal, Other, serving as a consultant: BMS, Merck & Co., Inc., Rahway, NJ, USA, Roche, Novartis, Amgen, GSK, and Sanofi. A. Italiano: Financial Interests, Personal, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; AstraZeneca; Merck Serono; and Bayer; Financial Interests, Personal, Other, Personal fees: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; AstraZeneca; Bayer; Bristol Myers Squibb; Epizyme; and Roche. L. Yao: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. A. Gozman: 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. F.J. Jin: 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. M. Maio: Financial Interests, Personal, Advisory Board: Roche; Bristol Myers Squibb; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Incyte; AstraZeneca; Amgen; Pierre Fabre; Eli Lilly; GlaxoSmithKline; Sanofi; Alfasigma; Merck Serono; Financial Interests, Personal, Other, Honoraria: Roche, Bristol Myers Squibb; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; AstraZeneca; Amgen; Pierre Fabre; Eli Lilly; GlaxoSmithKline; Sciclone; Sanofi; Alfasigma; Merck Serono; Financial Interests, Personal, Stocks/Shares: Epigen Therapeutics, and Theravance. All other authors have declared no conflicts of interest.