Medline ® Abstracts for References 40-42
of 'Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal cancer: Platinum-sensitive disease'
Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer.
Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV
Gynecol Oncol. 2015 Oct;139(1):10-6. Epub 2015 Aug 10.
OBJECTIVE: OCEANS is a randomized, placebo (PL)-controlled, phase 3 trial evaluating the efficacy and safety of bevacizumab combined with gemcitabine+carboplatin (GC) for patients with platinum-sensitive recurrent ovarian cancer (ROC). The study met its primary endpoint, demonstrating improved progression-free survival with GC+bevacizumab compared with GC+PL. Herein, we describe results of final overall survival (OS) and updated safety.
METHODS: Patients with recurrent platinum-sensitive ROC (recurring≥6months after first-line platinum-based therapy) and measurable disease at baseline were randomized to receive GC+bevacizumab or GC+PL for 6-10cycles; PL or bevacizumab was then continued until disease progression. In this updated analysis, a Cox proportional hazards model was used to compare OS between the 2 treatment arms.
RESULTS: At the data cutoff date (July 19, 2013), 353 patients (72.9%) had died. Median follow-up for OS was 58.2months in the experimental arm and 56.4months in the control arm. Consistent with interim analyses, median OS was comparable between arms (GC+bevacizumab: 33.6months; GC+PL: 32.9months; hazard ratio=0.95; log-rank p=0.65), and was consistent across all examined patient subgroups. The frequency and severity of adverse events were consistent with previous analyses; no new safety concerns were identified.
CONCLUSIONS: Results from final OS analysis of the phase 3 OCEANS study showed no significant difference in OS for patients treated with GC+bevacizumab compared with GC+PL.
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. Electronic address: firstname.lastname@example.org.
OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer.
Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR
J Clin Oncol. 2012;30(17):2039. Epub 2012 Apr 23.
PURPOSE: This randomized, multicenter, blinded, placebo-controlled phase III trial tested the efficacy and safety of bevacizumab (BV) with gemcitabine and carboplatin (GC) compared with GC in platinum-sensitive recurrent ovarian, primary peritoneal, or fallopian tube cancer (ROC).
PATIENTS AND METHODS: Patients with platinum-sensitive ROC (recurrence≥6 months after front-line platinum-based therapy) and measurable disease were randomly assigned to GC plus either BV or placebo (PL) for six to 10 cycles. BV or PL, respectively, was then continued until disease progression. The primary end point was progression-free survival (PFS) by RECIST; secondary end points were objective response rate, duration of response (DOR), overall survival, and safety.
RESULTS: Overall, 484 patients were randomly assigned. PFS for the BV arm was superior to that for the PL arm (hazard ratio [HR], 0.484; 95% CI, 0.388 to 0.605; log-rank P<.0001); median PFS was 12.4 v 8.4 months, respectively. The objective response rate (78.5% v 57.4%; P<.0001) and DOR (10.4 v 7.4 months; HR, 0.534; 95% CI, 0.408 to 0.698) were significantly improved with the addition of BV. No new safety concerns were noted. Grade 3 or higher hypertension (17.4% v<1%) and proteinuria (8.5% v<1%) occurred more frequently in the BV arm. The rates of neutropenia and febrile neutropenia were similar in both arms. Two patients in the BV arm experienced GI perforation after study treatment discontinuation.
CONCLUSION: GC plus BV followed by BV until progression resulted in a statistically significant improvement in PFS compared with GC plus PL in platinum-sensitive ROC.
Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. email@example.com
Independent radiologic review: bevacizumab in combination with gemcitabine and carboplatin in recurrent ovarian cancer.
Aghajanian C, Goff B, Nycum LR, Wang Y, Husain A, Blank S
Gynecol Oncol. 2014 Apr;133(1):105-10. Epub 2014 Feb 6.
OBJECTIVE: OCEANS, a randomized, placebo-controlled, phase III trial, found that adding bevacizumab to gemcitabine-carboplatin (GC) significantly improved investigator-determined progression-free survival (PFS) and objective response rate (ORR) in platinum-sensitive, recurrent ovarian cancer. To evaluate the reliability of assessment of progression and objective response per RECIST, radiologic and clinical data were assessed by an independent review committee (IRC).
METHODS: Radiologic images and clinical data were provided prospectively to the IRC for all randomized patients (N=484). Data were reviewed in a blinded fashion per RECIST (modified v1.0). PFS and ORR were analyzed based on the IRC assessment. Concordance between investigator- and IRC-assessed progression and objective response was assessed.
RESULTS: The IRC analysis demonstrated a statistically significant increase in PFS (hazard ratio [HR]=0.451; 95% confidence interval [CI]=0.351 to 0.580, p<0.0001) consistent with the benefit reported by investigators (HR=0.484; 95% CI=0.388 to 0.605, p<0.0001). The concordance rate, defined by agreement on progression status, was 74.2% overall, and comparable between treatment arms (bevacizumab, 75.2% vs. placebo, 73.1%). IRC-assessed ORR was significantly improved with bevacizumab (bevacizumab, 74.8% vs. placebo, 53.7%; p<0.0001), consistent with the investigator-assessed results. The concordance rate for objective response was 79.8% overall, and comparable between treatment arms (bevacizumab, 78.9% vs. placebo, 80.6%).
CONCLUSIONS: IRC-determined results were highly consistent with those determined by investigators, demonstrating that bevacizumab plus GC provides a significant improvement in PFS and ORR. These results suggest that investigators can reliably assess disease progression and objective response in recurrent ovarian cancer using RECIST, without the necessity of a full IRC review.
Memorial Sloan-Kettering Cancer Center, Gynecologic Medical Oncology Service, 300 East 66th Street, New York, NY 10065, USA; Weill Cornell Medical College, 445 East 69th Street, New York, NY 10021, USA. Electronic address: firstname.lastname@example.org.