TY - JOUR
T1 - Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma
T2 - An NRG oncology/gynecologic oncology group study
AU - Huh, Warner K.
AU - Brady, William E.
AU - Fracasso, Paula M.
AU - Dizon, Don S.
AU - Powell, Matthew A.
AU - Monk, Bradley J.
AU - Leath, Charles A.
AU - Landrum, Lisa M.
AU - Tanner, Edward J.
AU - Crane, Erin K.
AU - Ueda, Stefanie
AU - McHale, Michael T.
AU - Aghajanian, Carol
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - HPV
KW - Immunotherapy
KW - Listeria
KW - Metastatic
KW - Recurrent cervical cancer
UR - http://www.scopus.com/inward/record.url?scp=85087489829&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2020.06.493
DO - 10.1016/j.ygyno.2020.06.493
M3 - Article
C2 - 32641240
AN - SCOPUS:85087489829
SN - 0090-8258
VL - 158
SP - 562
EP - 569
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 3
ER -