Efficacy and safety of standard of care with/without bevacizumab for platinum-resistant ovarian/fallopian tube/peritoneal cancer previously treated with bevacizumab: The Japanese Gynecologic Oncology Group study JGOG3023

Abstract

We investigated the efficacy and safety of further bevacizumab therapy in patients with platinum-resistant ovarian cancer whose disease had progressed after bevacizumab plus chemotherapy. In this multicenter, open-label, phase II trial (JGOG3023), patients were randomized 1:1 to a single-agent chemotherapy alone (either pegylated liposomal doxorubicin [40 or 50 mg/m² administered intravenously], topotecan [1.25 mg/m² intravenously], paclitaxel [80 mg/m² intravenously], or gemcitabine [1000 mg/m² intravenously]) or single-agent chemotherapy + bevacizumab (15 mg/m² intravenously). The primary endpoint was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary endpoints were overall survival (OS), objective response rate (ORR), and response rate according to Gynecological Cancer Intergroup cancer antigen 125 criteria. In total, 103 patients were allocated to chemotherapy (n = 51) or chemotherapy + bevacizumab (n = 52). Median investigator-assessed PFS was 3.1 and 4.0 mo in each group, respectively (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.32-0.90, P = .0082). Median OS was 11.3 and 15.3 mo in each group, respectively (HR = 0.67, 95% CI: 0.38-1.17, P = .1556). Respective ORRs were 13.7% and 25.0% (P = .0599) and response rates were 16.7% and 21.4% (P = .8273). The incidence of grade ≥3 treatment-related AEs was 42.0% in the chemotherapy group and 54.9% in the chemotherapy + bevacizumab group; AEs were well tolerated, with only 2 and 12 events leading to discontinuation of therapy, respectively. Bevacizumab was effective beyond progressive disease and AEs were manageable. The observed improvement in PFS requires further verification.

Keywords: bevacizumab; fallopian tube cancer; ovarian cancer; peritoneal cancer; platinum resistance.

FIGURE 1

Patient disposition. Data are n (%). ^aThe reasons for discontinuation were as follows. In 1 case, the dosing regimen assigned to the patient was not approved. In another case, the patient's protein to creatinine ratio (1.3) was found to be above that established as an eligibility criterion for this study (≤1.0). ^bTwo patients were misallocated to the chemotherapy group and received bevacizumab; these patients were included in the chemotherapy group for efficacy analyses and in the chemotherapy + bevacizumab group for safety analyses. One patient allocated to the chemotherapy + bevacizumab group received chemotherapy alone (without bevacizumab) and was included in the chemotherapy + bevacizumab group for efficacy analysis and the chemotherapy group for safety analysis. BEV, bevacizumab; CT, chemotherapy; ITT, intention to treat

FIGURE 2

Kaplan‐Meier curve for investigator‐assessed progression‐free survival (A) and forest plot of progression‐free survival and interaction term test based on a multivariate Cox regression model (B) (intent‐to‐treat analysis set). BEV, bevacizumab; CI, confidence interval; CT, chemotherapy

FIGURE 3

Kaplan‐Meier curve for overall survival (A) and forest plot of overall survival and interaction term test based on a multivariate Cox regression model (B) (intent‐to‐treat analysis set). BEV, bevacizumab; CI, confidence interval; CT, chemotherapy