Linda R Duska1, Jennifer M Scalici2, Sarah M Temkin3, Julie K Schwarz4, Erin K Crane5, Katherine M Moxley6, Chad A Hamilton7, Stephanie L Wethington8, Gina R Petroni9, Nikole E Varhegyi9, Sheena H Clift1, Timothy N J Bullock10, Timothy N Showalter11. 1. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, Virginia. 2. Mitchell Cancer Institute, USA Health, Mobile, Alabama. 3. Anne Arundel Medical Center, Annapolis, Maryland. 4. Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, Missouri. 5. Division of Gynecologic Oncology, Levine Cancer Institute, Charlotte, North Carolina. 6. Stephenson Cancer Center, University of Oklahoma Sciences Center, Oklahoma City, Oklahoma. 7. Inova Schar Cancer Institute, Fairfax, Virginia. 8. Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, Maryland. 9. Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia. 10. Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia. 11. Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia.
Abstract
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.
RCT Entities:
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.
Authors: J M Herter; M Kiljan; S Kunze; M Reinscheid; O Ibruli; J Cai; L Niu; I Heßelmann; M Trommer; G S Herter-Sprie; C Köhler; S Marnitz Journal: Strahlenther Onkol Date: 2022-10-17 Impact factor: 4.033
Authors: Casey W Williamson; Michael V Sherer; Dmitriy Zamarin; Andrew B Sharabi; Brandon A Dyer; Loren K Mell; Jyoti S Mayadev Journal: Cancer Date: 2021-02-23 Impact factor: 6.921