PMID- 32910478 OWN - NLM STAT- MEDLINE DCOM- 20210608 LR - 20210608 IS - 1097-0142 (Electronic) IS - 0008-543X (Linking) VI - 126 IP - 22 DP - 2020 Nov 15 TI - Results of an early safety analysis of a study of the combination of pembrolizumab and pelvic chemoradiation in locally advanced cervical cancer. PG - 4948-4956 LID - 10.1002/cncr.33136 [doi] AB - BACKGROUND: Immune checkpoint inhibitors are being considered for locally advanced cervical cancer (LACC) together with standard-of-care pelvic chemoradiation (CRT). However, the safety of the combination and its optimal schedule are unknown. Defining the safety of the combination is a primary objective of a study examining concurrent and sequential schedules. This article presents a safety analysis that was fully accrued and met reporting requirements. METHODS: Pembrolizumab was given after CRT (arm 1) or during CRT (arm 2) according to a randomized phase 2 design. Patients who were 18 years old or older and had LACC (stages IB-IVA according to the 2009 International Federation of Gynecology and Obstetrics system) were randomized 1:1 to the treatment regimens. The CRT was identical in the 2 arms. Pembrolizumab was administered every 3 weeks for 3 doses; no maintenance was allowed. All patients receiving any treatment were evaluated for safety. Safety assessments included the incidence and severity of adverse events (AEs) and the occurrence of protocol-defined dose-limiting toxicity (DLT) through 30 days after the last pembrolizumab infusion. RESULTS: As of August 2019, 52 of the 88 planned patients had completed treatment and were evaluable for toxicity. Treatment-related grade 2 or higher toxicity was experienced by 88%; 11 had at least 1 grade 4 AE, and another 23 had at least 1 grade 3 AE. Grade 1 or higher diarrhea was reported in 34 patients (65%; 50% of these were grade 1), and there was no difference between arms (63% in arm 1 vs 68% in arm 2). Two patients experienced 3 DLTs. Most patients completed cisplatin (100% in arm 1 vs 82% in arm 2); 83% in both arms completed all pembrolizumab. CONCLUSIONS: Preliminary results support the safety and feasibility of adding pembrolizumab to pelvic CRT concurrently or sequentially. LAY SUMMARY: Pembrolizumab is a humanized antibody against programmed cell death protein 1 that is used in cancer immunotherapy. Preliminary data suggest that pembrolizumab can be safely combined with chemotherapy and pelvic radiation in the treatment of locally advanced cervical cancer. Future studies of the addition of immunotherapy to traditional chemoradiation are planned to determine the best way to deliver the treatment and whether any improvement is seen with the addition of immunotherapy to traditional therapy. CI - (c) 2020 American Cancer Society. FAU - Duska, Linda R AU - Duska LR AUID- ORCID: 0000-0002-8878-4123 AD - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, Virginia. FAU - Scalici, Jennifer M AU - Scalici JM AD - Mitchell Cancer Institute, USA Health, Mobile, Alabama. FAU - Temkin, Sarah M AU - Temkin SM AUID- ORCID: 0000-0002-6472-2745 AD - Anne Arundel Medical Center, Annapolis, Maryland. FAU - Schwarz, Julie K AU - Schwarz JK AD - Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, Missouri. FAU - Crane, Erin K AU - Crane EK AD - Division of Gynecologic Oncology, Levine Cancer Institute, Charlotte, North Carolina. FAU - Moxley, Katherine M AU - Moxley KM AD - Stephenson Cancer Center, University of Oklahoma Sciences Center, Oklahoma City, Oklahoma. FAU - Hamilton, Chad A AU - Hamilton CA AD - Inova Schar Cancer Institute, Fairfax, Virginia. FAU - Wethington, Stephanie L AU - Wethington SL AD - Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, Maryland. FAU - Petroni, Gina R AU - Petroni GR AD - Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia. FAU - Varhegyi, Nikole E AU - Varhegyi NE AD - Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia. FAU - Clift, Sheena H AU - Clift SH AD - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, Virginia. FAU - Bullock, Timothy N J AU - Bullock TNJ AD - Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia. FAU - Showalter, Timothy N AU - Showalter TN AD - Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia. LA - eng GR - Merck Pharmaceuticals/ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200910 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Antibodies, Monoclonal, Humanized) RN - DPT0O3T46P (pembrolizumab) SB - IM MH - Antibodies, Monoclonal, Humanized/pharmacology/*therapeutic use MH - Female MH - Humans MH - Male MH - Pelvis/*pathology MH - Uterine Cervical Neoplasms/*drug therapy/*radiotherapy OTO - NOTNLM OT - cervical cancer OT - chemoradiation OT - combination OT - immunotherapy OT - safety EDAT- 2020/09/11 06:00 MHDA- 2021/06/09 06:00 CRDT- 2020/09/10 12:28 PHST- 2020/05/21 00:00 [received] PHST- 2020/07/03 00:00 [revised] PHST- 2020/07/09 00:00 [accepted] PHST- 2020/09/11 06:00 [pubmed] PHST- 2021/06/09 06:00 [medline] PHST- 2020/09/10 12:28 [entrez] AID - 10.1002/cncr.33136 [doi] PST - ppublish SO - Cancer. 2020 Nov 15;126(22):4948-4956. doi: 10.1002/cncr.33136. Epub 2020 Sep 10.