CHICAGO—Adding bevacizumab to neoadjuvant chemotherapy did not improve complete macroscopic response rate (CMR) or progression-free survival (PFS) among women with newly diagnosed, advanced, initially unresectable epithelial ovarian cancer, according to study results (abstract 5508) from the phase II, randomized, multicenter NOVA trial, presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6.
“Although neoadjuvant chemotherapy plus bevacizumab improved surgical feasibility at IDS [interval debulking surgery], neither the rate of optimal cytoreduction nor PFS was improved with 3–4 additional preoperative cycles of bevacizumab,” reported Yolanda Garcia, MD, of the Hospital Parc Tauli Sabadell in Sabadell, Spain.
Standard treatment for advanced epithelial ovarian cancer is primary debulking surgery followed by adjuvant combination chemotherapy with carboplatin plus paclitaxel, with or without bevacizumab. Little is known about bevacizumab’s potential role in neoadjuvant therapy for these patients, however.
The study authors therefore undertook a phase II open-label study of 68 evaluable patients with newly diagnosed, unresectable, high-grade serous or endometrioid epithelial ovarian cancer, FIGO stages III or IV, with ECOG performance status scores of 0 to 2. Patients with intestinal occlusion or bevacizumab contraindications were excluded from the study.
Participants were randomly assigned to receive 4 neoadjuvant courses of triweekly carboplatin (AUC 6) and paclitaxel (intravenous 175 mg/m2), with (n = 35) or without (n = 33) at least 3 courses of bevacizumab (15 mg/kg every 3 weeks). Following surgery, patients from both groups received 3 cycles of chemotherapy with bevacizumab and bevacizumab maintenance therapy for up to 15 months.
The two study groups were well balanced in terms of tumor location, ECOG performance status scores, FIGO stage, and histology. Of the patients enrolled, 22 in the chemotherapy-alone group and 31 of the bevacizumab group underwent surgery; 19 and 29 initiated adjuvant chemotherapy plus bevacizumab.
CMR following IDS was the primary study endpoint. Secondary endpoints included safety, surgical feasibility, optimal cytoreduction surgery rate, response rate, and PFS.
No differences in CMR were seen between the two study groups following surgery. No differences were found in optimal surgery rates.
Suboptimal surgical outcomes were seen for 1 patient in the chemotherapy-alone group and 8 in the bevacizumab group (3% vs 23%; P = .028).
The bevacizumab arm was favored in rates of surgical feasibility (67% vs 89%; P = .029), Garcia noted.
Median PFS was comparable between the two groups (20.1 vs 20.4 months).
However, in part because bevacizumab did not increase overall serious toxicity rates, Garcia suggested that “carefully selected high-risk patients” with unresectable disease at diagnosis might benefit from early integration of bevacizumab into neoadjuvant chemotherapy. Grade 3 or higher adverse events were less frequent in the bevacizumab group at any time during the study (79% vs 54%; P = .033) and during neoadjuvant treatment (61% vs 29%; P = .008). Neutropenia was seen in one patient in each study group, and two patients in the bevacizumab group developed neutropenia with fever. One patient in the bevacizumab group died of postoperative sepsis.