343 - Phase 3 Study of Pembrolizumab (Pembro) + Adjuvant Chemotherapy (CT) ± Radiotherapy (RT) for Newly Diagnosed, High-Risk Endometrial Cancer (EC): Exploratory Analysis of Disease-Specific-Free Survival (DSFS) and Safety by Radiation Usage
Presenter(s)
J. S. Mayadev1,2, T. Piatnytska3,4, W. Lv5, F. Ortaç6,7, K. Hasegawa8, H. Dahlstrand9,10, A. Santin11, R. Autorino12,13, A. Danska-Bidzinska14,15, S. García Cabezas16,17, K. Vera18, Y. M. Kim19, S. Crafton2,20, G. Tasca21, S. Kruger22, E. Jensen22, R. Orlowski22, A. Leary23,24, and T. Van Gorp25,26; 1Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 2GOG Foundation, Philadelphia, PA, 3Department of Gynecologic Oncology, Khmelnytskyi Regional Anti-Tumor Center, Khmelnytskyi, Ukraine, 4CEEGOG, Prague, Czech Republic, 5Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China, 6Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, Ankara University School of Medicine, Ankara, Turkey, 7TRSGO, Istanbul, Turkey, 8Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama Prefecture, Japan, 9NSGO-CTU, Copenhagen, Denmark, and Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden, 10Department of Gynecologic Oncology, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden, 11Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, 12Department of Radiation Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, 13MITO, Rome, Italy, 14Department of Gynecological Oncology, 2nd Division of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland, 15PGOG, Warsaw, Poland, 16Department of Radiation Oncology, Reina Sofia University Hospital, Cordoba, Spain, 17GEICO, Madrid, Spain, 18Hospital Británico, Buenos Aires, Argentina, 19Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan, Seoul, Korea, Republic of (South), 20Gynecologic Oncology, West Penn Hospital, Allegheny Health Network, Pittsburgh, PA, 21Veneto Institute of Oncology IOV – IRCCS, Padua, Italy, 22Merck & Co., Inc., Rahway, NJ, 23Department of Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France, 24GINECO, Paris, France, 25Division of Gynaecological Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium, 26BGOG, Leuven, Belgium
Purpose/Objective(s):
In ENGOT-en11/GOG-3053/KEYNOTE-B21 (NCT04634877), pembro (vs placebo [pbo]) + CT (± RT) did not improve DFS (HR, 1.02; 95% CI, 0.79–1.32; P = 0.570) in participants (pts) with newly diagnosed, high-risk EC; pembro improved DFS in dMMR (HR, 0.31; 95% CI, 0.14-0.69) but not pMMR (HR, 1.20; 95% CI, 0.91–1.57) EC. We report exploratory analysis of DSFS in pMMR EC and safety by RT usage.Materials/Methods:
Pts (=18 y) with high-risk EC (FIGO 2009 stage I/II of nonendometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA) following surgery with curative intent (no evidence of disease) were randomized to pembro 200 mg or pbo Q3W for 6 cycles + carboplatin-paclitaxel, then 6 cycles of pembro 400 mg or pbo Q6W, respectively. At investigator discretion, RT (EBRT or EBRT + radiosensitizing cisplatin) was administered after completion of 6 or 4 cycles, respectively, of CT; both approaches can incorporate brachytherapy (BT). Randomization was stratified by MMR status and, within the pMMR subgroup, by planned RT, histology, and surgical stage. DSFS was defined as time from randomization to local or distant recurrence of EC or death due to EC.Results:
In pMMR EC, RT usage was similar between treatment arms, with ~56% of pts receiving EBRT (Table); at data cutoff (Mar 4, 2024), HR (95% CI) for DSFS was 1.14 (0.70–1.85), 0.80 (0.44–1.44), 1.09 (0.32–3.79), and 1.36 (0.84–2.21) in pts receiving EBRT + BT, EBRT, BT, and no EBRT/BT, respectively. Most pts had AEs during RT, with lower rates in the BT vs EBRT + BT or EBRT groups (Table).Conclusion:
In pMMR EC, addition of pembro (vs pbo) to CT did not improve DSFS regardless of RT usage. Safety was manageable across all RT groups, with no evidence of long-term toxicity. Abstract 343 - Table 1| Pembro + CT | Pbo + CT | |||||||||||
| pMMR subgroup | EBRT + BT n = 113 | EBRT n = 110 | BT n = 33 | No EBRT/BT n = 148 | EBRT + BT n = 126 | EBRT n = 110 | BT n = 36 | No EBRT/BT n = 138 | ||||
| Planned RT, n (%) | ||||||||||||
| Chemo-EBRT/ EBRT + BT | 108 (96) | 12 (11) | 1 (3) | 16 (11) | 123 (98) | 14 (13) | 1 (3) | 9 (7) | ||||
| Chemo-EBRT | 2 (2) | 34 (31) | 0 | 1 (1) | 1 (1) | 36 (33) | 0 | 3 (2) | ||||
| EBRT | 2 (2) | 61 (55) | 0 | 8 (5) | 2 (2) | 58 (53) | 0 | 3 (2) | ||||
| BT | 1 (1) | 2 (2) | 32 (97) | 5 (3) | 0 | 2 (2) | 35 (97) | 6 (4) | ||||
| No EBRT/BT | 0 | 1 (1) | 0 | 118 (80) | 0 | 0 | 0 | 117 (85) | ||||
| RT duration, median (range), d | 47 (36–102) | 37 (18–50) | 14 (3–22) | - | 47 (36–118) | 38 (3–73) | 11 (5–17) | - | ||||
| EBRT dose, median (range), Gy | 45 (44–60.8) | 46 (23.4–60.2) | - | - | 45 (45–50.4) | 45 (6–66) | - | - | ||||
| BT HDR dose, median (range), Gy | 12 (6–30) | - | 21 (14–31.5) | - | 12 (6–30) | - | 21 (21–31.5) | - | ||||
| Pembro + CT | Pbo + CT | |||||||||||
| All pts | EBRT + BT n = 160 | EBRT n = 162 | BT n = 43 | EBRT + BT n = 177 | EBRT n = 147 | BT n = 43 | ||||||
| AEs during/after RT, n (%) | ||||||||||||
| Any | 153 (96) / 88 (55) | 157 (97) / 86 (53) | 39 (91) / 17 (40) | 163 (92) / 83 (47) | 140 (95) / 83 (56) | 38 (88) / 21 (49) | ||||||
| Treatment related | 136 (85) / 35 (22) | 141 (87) / 33 (20) | 31 (72) / 5 (12) | 144 (81) / 16 (9) | 120 (82) / 24 (16) | 28 (65) / 4 (9) | ||||||
| Grade =3 treatment related | 49 (31) / 3 (2) | 62 (38) / 4 (2) | 2 (5) / 1 (2) | 41 (23) / 1 (1) | 43 (29) / 1 (1) | 4 (9) / 1 (2) | ||||||