TY - JOUR
T1 - Randomized phase IIB evaluation of weekly paclitaxel versus weekly paclitaxel with oncolytic reovirus (Reolysin®) in recurrent ovarian, tubal, or peritoneal cancer
T2 - An NRG Oncology/Gynecologic Oncology Group study
AU - Cohn, David E.
AU - Sill, Michael W.
AU - Walker, Joan L.
AU - O'Malley, David
AU - Nagel, Christa I.
AU - Rutledge, Teresa L.
AU - Bradley, William
AU - Richardson, Debra L.
AU - Moxley, Katherine M.
AU - Aghajanian, Carol
N1 - Funding Information:
This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical Office (CA 37517), NRG Oncology (1 U10 CA180822) and NRG Operations (U10CA180868). The following Gynecologic Oncology institutions participated in this study: Ohio State University Comprehensive Cancer Center, University of Oklahoma Health Sciences Center, University of New Mexico, Case Western Reserve University, Carillion Clinic Gynecological Oncology, Froedtert and the Medical College of Wisconsin, University of New Mexico, University of Texas Southwestern Medical Center, Indiana University Hospital/Melvin and Bren Simon Cancer Center, University of Mississippi Medical Center, Wake Forest University Health Sciences, Women's Cancer Center of Nevada and Mayo Clinic.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/9
Y1 - 2017/9
N2 - Objective To assess whether the addition of oncolytic reovirus (Reolysin®) to weekly paclitaxel prolonged progression-free survival (PFS) in the treatment of women with recurrent or persistent ovarian, tubal or primary peritoneal cancer. Patients and methods Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to paclitaxel (80 mg/m2 intravenously days 1, 8, and 15 every 4 weeks) or the combination of paclitaxel (80 mg/m2 intravenously days 1, 8, and 15) plus reovirus 3 × 1010 TCID50/day intravenously on days 1–5, both every 4 weeks until disease progression or toxicity. The primary end point was PFS. The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%. Results The study accrued 108 patients, 100 of whom were evaluable for toxicity. Median PFS was 4.3 months for paclitaxel and 4.4 months for paclitaxel plus reovirus (hazard ratio, 1.11; 90% two-sided CI, 0.78 to 1.59; one-sided P = 0.687). The proportion responding (overall response rate) to paclitaxel was 20% among 45 patients with measurable disease receiving paclitaxel alone, and 17.4% among the 46 patients treated with the combination. The asymptotic relative probability of responding was 0.87 (90% CI, 0.42 to 1.79). Severe adverse events were more common in the combination regimen than in paclitaxel arm for severe neutropenia (grade ≥ 4, 12% versus 0%), and severe respiratory adverse events (grade ≥ 3, 25% versus 2%). No deaths were considered treatment related. Conclusion The addition of reovirus to weekly paclitaxel in the treatment of women with recurrent or persistent ovarian, tubal or peritoneal cancer did not sufficiently reduce the hazard of progression or death to warrant further investigation.
AB - Objective To assess whether the addition of oncolytic reovirus (Reolysin®) to weekly paclitaxel prolonged progression-free survival (PFS) in the treatment of women with recurrent or persistent ovarian, tubal or primary peritoneal cancer. Patients and methods Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to paclitaxel (80 mg/m2 intravenously days 1, 8, and 15 every 4 weeks) or the combination of paclitaxel (80 mg/m2 intravenously days 1, 8, and 15) plus reovirus 3 × 1010 TCID50/day intravenously on days 1–5, both every 4 weeks until disease progression or toxicity. The primary end point was PFS. The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%. Results The study accrued 108 patients, 100 of whom were evaluable for toxicity. Median PFS was 4.3 months for paclitaxel and 4.4 months for paclitaxel plus reovirus (hazard ratio, 1.11; 90% two-sided CI, 0.78 to 1.59; one-sided P = 0.687). The proportion responding (overall response rate) to paclitaxel was 20% among 45 patients with measurable disease receiving paclitaxel alone, and 17.4% among the 46 patients treated with the combination. The asymptotic relative probability of responding was 0.87 (90% CI, 0.42 to 1.79). Severe adverse events were more common in the combination regimen than in paclitaxel arm for severe neutropenia (grade ≥ 4, 12% versus 0%), and severe respiratory adverse events (grade ≥ 3, 25% versus 2%). No deaths were considered treatment related. Conclusion The addition of reovirus to weekly paclitaxel in the treatment of women with recurrent or persistent ovarian, tubal or peritoneal cancer did not sufficiently reduce the hazard of progression or death to warrant further investigation.
KW - Oncolytic virus
KW - Paclitaxel
KW - Recurrent ovarian cancer
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U2 - 10.1016/j.ygyno.2017.07.135
DO - 10.1016/j.ygyno.2017.07.135
M3 - Article
C2 - 28756871
AN - SCOPUS:85026308792
SN - 0090-8258
VL - 146
SP - 477
EP - 483
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 3
ER -