Alessandro D Santin1, Wei Deng2, Michael Frumovitz3, Natalia Buza4, Stefania Bellone5, Warner Huh6, Samir Khleif7, Heather A Lankes8, Elena S Ratner9, Roisin E O'Cearbhaill10, Amir A Jazaeri11, Michael Birrer12. 1. Yale University School of Medicine, New Haven, CT, United States of America. Electronic address: Alessandro.santin@yale.edu. 2. NRG Oncology SDMC, CTD Division, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States of America. Electronic address: dengw@nrgoncology.edu. 3. Dept. of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America. Electronic address: mfrumovitz@mdanderson.org. 4. Yale University School of Medicine, New Haven, CT, United States of America. Electronic address: Natalia.buza@yale.edu. 5. Yale University School of Medicine, New Haven, CT, United States of America. Electronic address: Stefania.bellone@yale.edu. 6. University of Alabama at Birmingham, Birmingham, AL, United States of America. Electronic address: whuh@uabmc.edu. 7. The Loop Immuno-Oncology Research Laboratory, Lombardi Cancer Center, Georgetown University, Washington, DC, United States of America. Electronic address: skhleif@augusta.edu. 8. Biopathology Center, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States of America; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH, United States of America. Electronic address: LankesH@NRGOncology.org. 9. Department of Gynecologic Oncology, Gynecology, Obstetrics, Yale University, New Haven, CT, United States of America. Electronic address: elena.ratner@yale.edu. 10. Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America. Electronic address: ocearbhr@mskcc.org. 11. Dept. of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America. Electronic address: AAJazaeri@mdanderson.org. 12. Department of Oncology, University of Alabama Comprehensive Cancer Center, Birmingham, AL, United States of America. Electronic address: mbirrer@uab.edu.
Abstract
PURPOSE: Patients with persistent/recurrent cervical cancer following platinum-based chemotherapy have limited therapeutic options. The Gynecologic-Oncology-Group conducted a phase II trial to assess efficacy and tolerability of nivolumab, an immune checkpoint inhibitor, in persistent/recurrent cervical carcinoma. PATIENTS AND METHODS: Key eligibility criteria included persistent/recurrent cervical cancer, failure of prior systemic therapy and ECOG PS 0-1. Nivolumab 3 mg/kg was given IV every 2 wk. until disease progression or intolerable toxicity. Response was assessed every 8 wk. for 6 months and every 12 wk. thereafter. The primary endpoints were objective response as assessed by RECIST 1.1. The study used a 2-stage group sequential design. PD-L1 expression was evaluated in tumor specimens by immunohistochemistry (IHC) using a combined-positive-score (CPS) cutoff of ≥1%. RESULTS: Of 26 enrolled patients with persistent/recurrent cervical cancer, 25 were evaluable for response/toxicity with a median age of 45. 36% had ECOG PS of 1, and 100% had received one prior systemic chemotherapy regimen. PD-L1 expression (≥1%) was identified in 77.3% of tumor samples. As of 03/05/19, all patients were off study treatment; median follow-up for survival status was 32 months (range, 2-41.5). There were 21 (84%) patients with a treatment-related adverse event (TRAE) and most were grades 1-2. Six (24%) patients had grade 3 TRAEs with 1 discontinuing nivolumab due to hepatic toxicity. No grade 5 TRAEs occurred, and 2 patients had grade 4 TRAEs. One confirmed partial response (4%; 90% CI, 0.4%-22.9%), duration of response 3.8 months. Thirty-six percent of patients had stable disease (SD) (9/25; 90% CI, 20.2%-54.4%); the median duration of SD was 5.7 months (range, 3.5-12.7). Estimated PFS and OS at 6 months were 16% and 78.4%, respectively. CONCLUSION: Single agent nivolumab exhibited low antitumor activity and an acceptable safety profile in patients with persistent/recurrent cervical cancer previously treated with platinum-based chemotherapy.
PURPOSE:Patients with persistent/recurrent cervical cancer following platinum-based chemotherapy have limited therapeutic options. The Gynecologic-Oncology-Group conducted a phase II trial to assess efficacy and tolerability of nivolumab, an immune checkpoint inhibitor, in persistent/recurrent cervical carcinoma. PATIENTS AND METHODS: Key eligibility criteria included persistent/recurrent cervical cancer, failure of prior systemic therapy and ECOG PS 0-1. Nivolumab 3 mg/kg was given IV every 2 wk. until disease progression or intolerable toxicity. Response was assessed every 8 wk. for 6 months and every 12 wk. thereafter. The primary endpoints were objective response as assessed by RECIST 1.1. The study used a 2-stage group sequential design. PD-L1 expression was evaluated in tumor specimens by immunohistochemistry (IHC) using a combined-positive-score (CPS) cutoff of ≥1%. RESULTS: Of 26 enrolled patients with persistent/recurrent cervical cancer, 25 were evaluable for response/toxicity with a median age of 45. 36% had ECOG PS of 1, and 100% had received one prior systemic chemotherapy regimen. PD-L1 expression (≥1%) was identified in 77.3% of tumor samples. As of 03/05/19, all patients were off study treatment; median follow-up for survival status was 32 months (range, 2-41.5). There were 21 (84%) patients with a treatment-related adverse event (TRAE) and most were grades 1-2. Six (24%) patients had grade 3 TRAEs with 1 discontinuing nivolumab due to hepatic toxicity. No grade 5 TRAEs occurred, and 2 patients had grade 4 TRAEs. One confirmed partial response (4%; 90% CI, 0.4%-22.9%), duration of response 3.8 months. Thirty-six percent of patients had stable disease (SD) (9/25; 90% CI, 20.2%-54.4%); the median duration of SD was 5.7 months (range, 3.5-12.7). Estimated PFS and OS at 6 months were 16% and 78.4%, respectively. CONCLUSION: Single agent nivolumab exhibited low antitumor activity and an acceptable safety profile in patients with persistent/recurrent cervical cancer previously treated with platinum-based chemotherapy.
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