Warner K Huh1, William E Brady2, Paula M Fracasso3, Don S Dizon4, Matthew A Powell5, Bradley J Monk6, Charles A Leath7, Lisa M Landrum8, Edward J Tanner9, Erin K Crane10, Stefanie Ueda11, Michael T McHale12, Carol Aghajanian13. 1. University of Alabama at Birmingham, Division of Gynecologic Oncology, Birmingham, AL 35249, United States of America. Electronic address: whuh@uabmc.edu. 2. NRG Oncology, Clinical Trial Development Division, Biostatistics & Bioinformatics, Roswell Park, Buffalo, NY 14263, United States of America. 3. Department of Medicine, University of Virginia, UVA Cancer Center, Charlottesville, VA 22908, United States of America. Electronic address: fracasso@virginia.edu. 4. Division of Hematology-Oncology, Lifespan Cancer Institute, Rhode Island Hospital, Department of Medicine, Alpert Medical School of Brown University, Providence, RI 02903, United States of America. 5. Washington University School of Medicine, Saint Louis, MO 63110, United States of America. Electronic address: mpowell@wustl.edu. 6. Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine at St. Joseph Hospital, Phoenix, AZ 85016, United States of America. Electronic address: Monk@usoncology.com. 7. University of Alabama at Birmingham, Division of Gynecologic Oncology, Birmingham, AL 35249, United States of America. Electronic address: cleath@uabmc.edu. 8. Oklahoma University Health Science Center, OB/GYN, Oklahoma City, OK 73104, United States of America. Electronic address: lisa-landrum@ouhsc.edu. 9. Johns Hopkins Medical Institutions, Baltimore, MD 21287, United States of America. Electronic address: etanner4@jhmi.edu. 10. Department of Gynecologic Oncology, Carolinas Medical Center, Levine Cancer Institute, Charlotte, NC 28203, United States of America. Electronic address: erin.crane@atriumhealth.org. 11. University of California, San Francisco, OB/GYN & Reproductive Sciences, Division of Gyn Onc., San Francisco, CA 94115, United States of America. Electronic address: UedaS2@obgyn.ucsf.edu. 12. Moores UCSD Cancer Center, La Jolla, CA 92093, United States of America. Electronic address: mtmchale@ucsd.edu. 13. Memorial Sloan-Kettering Cancer Center, Dept. of Medical Oncology, New York, NY 10021, United States of America. Electronic address: aghajanc@mskcc.org.
Abstract
OBJECTIVE: Women with persistent, recurrent, and/or metastatic cervical cancer have a poor prognosis. Even with the availability of cisplatin plus paclitaxel and bevacizumab, median overall survival (OS) is only 17.0 months, with median post-progression survival of approximately seven months. We studied the therapeutic vaccine, Axalimogene filolisbac (ADXS-HPV), in women who had progressed following at least one prior line of therapy (Gynecologic Oncology Group protocol 265/NCT01266460). METHODS: Volunteers ≥18 years with advanced cervical cancer and GOG performance status score of 0 or 1 were eligible for participation in this 2-stage, phase II trial. In stage 1, women received up to three doses of ADXS-HPV (1 × 109 colony-forming units in 250 mL IV over 15 min every 28 days) and were monitored for tumor progression. In stage 2, women were treated until progression, intolerable adverse events (AEs), or voluntary withdrawal of consent. Co-primary endpoints were safety and proportion of volunteers surviving ≥12 months. An estimated, combined (stages 1 + 2) 12-month OS of 35% was calculated from historical GOG cohorts to declare ADXS-HPV sufficiently active in this platinum-pre-treated population. Secondary endpoints were OS and progression-free survival (PFS). RESULTS: Among 50 evaluable volunteers, the 12-month OS was 38% (n = 19). Median OS was 6.1 months (95% CI: 4.3-12.1) and median PFS was 2.8 months (95% CI: 2.6-3.0). The most common treatment-related AEs were fatigue, chills, fever, nausea, and anemia. The majority of AEs were grade 1 or 2 and resolved spontaneously or with appropriate treatment. CONCLUSION: At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma.
OBJECTIVE:Women with persistent, recurrent, and/or metastatic cervical cancer have a poor prognosis. Even with the availability of cisplatin plus paclitaxel and bevacizumab, median overall survival (OS) is only 17.0 months, with median post-progression survival of approximately seven months. We studied the therapeutic vaccine, Axalimogene filolisbac (ADXS-HPV), in women who had progressed following at least one prior line of therapy (Gynecologic Oncology Group protocol 265/NCT01266460). METHODS: Volunteers ≥18 years with advanced cervical cancer and GOG performance status score of 0 or 1 were eligible for participation in this 2-stage, phase II trial. In stage 1, women received up to three doses of ADXS-HPV (1 × 109 colony-forming units in 250 mL IV over 15 min every 28 days) and were monitored for tumor progression. In stage 2, women were treated until progression, intolerable adverse events (AEs), or voluntary withdrawal of consent. Co-primary endpoints were safety and proportion of volunteers surviving ≥12 months. An estimated, combined (stages 1 + 2) 12-month OS of 35% was calculated from historical GOG cohorts to declare ADXS-HPV sufficiently active in this platinum-pre-treated population. Secondary endpoints were OS and progression-free survival (PFS). RESULTS: Among 50 evaluable volunteers, the 12-month OS was 38% (n = 19). Median OS was 6.1 months (95% CI: 4.3-12.1) and median PFS was 2.8 months (95% CI: 2.6-3.0). The most common treatment-related AEs were fatigue, chills, fever, nausea, and anemia. The majority of AEs were grade 1 or 2 and resolved spontaneously or with appropriate treatment. CONCLUSION: At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma.
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