Bevacizumab plus chemotherapy prolongs PFS for recurrent ovarian cancer
CHICAGO — Rechallenge treatment with bevacizumab in combination with platinum-based chemotherapy prolonged PFS among patients with recurrent ovarian cancer previously treated with first-line bevacizumab, according to phase 3 results presented at ASCO Annual Meeting.
Previous studies indicated bevacizumab (Avastin, Genentech) added to first-line carboplatin and paclitaxel chemotherapy, and as maintenance, prolongs PFS for stage IIIB to stage IV ovarian cancer. The drug is currently approved in Europe in combination with chemotherapy.
Sandro Pignata, MD, PhD, from the IRCCS National Cancer Institute “Fondazione G. Pascale” in Naples, Italy, and president of the Multicentre Italian Trial in Ovarian cancer group, and colleagues aimed to determine whether the addition of bevacizumab to a platinum-based chemotherapy improved PFS for patients who previously received it during first line.
Investigators randomly assigned 405 patients (median age, 61 years) to six cycles of platinum-based doublets — carboplatin/paclitaxel, carboplatin/gemcitabine or carboplatin/PLD — with (n = 203) or without (n = 205) bevacizumab.
Bevacizumab was administered concomitantly with chemotherapy and as maintenance until disease progression.
A majority of patients in both groups had serous tumors (79.8%).
Among the patients, 64% had progressive disease more than 1 year after last dose of platinum chemotherapy and 72% after completion of first-line bevacizumab maintenance.
Investigator-assessed PFS via RECIST 1.1 served as the primary endpoint. Secondary endpoints included OS, safety and objective response rate via RECIST 1.1. Other secondary endpoints for which data were unavailable included central review PFS and prognostic and predictive molecular factors.
The projected PFS in the bevacizumab-treated group was 11.9 months. The expected PFS in the standard group was 8 months.
At a median follow-up of 20.3 months, researchers reported 304 PFS events and 147 deaths.
Median PFS was 11.8 months among patients who received bevacizumab compared with 8.8 months among patients who did not (HR = 0.51; 95% CI, 0.41-0.64) when adjusted by age, performance, center size, rate of relapse and other factors.
“All the main variables in terms of prognostic factors and strata show benefit with the addition of bevacizumab,” Pignata said during his presentation.
The median OS was 26.7 months among patients who received bevacizumab compared with 27.1 months among patients who did not (HR = 1; 95% CI, 0.73-1.39).
“This [OS] analysis should not be considered mature,” Pignata said.
The ORR rate was 74.6% in the bevacizumab group compared with 65.7% in the standard group, which did not represent a significant difference.
Twenty patients in the bevacizumab group had a complete response compared with nine in the standard group, and 77 patients in the bevacizumab group had partial responses compared with 85 in the standard group.
“I think it is [still] important to note the number of complete responses is doubled in patients who received bevacizumab,” Pignata.
Important grade 3 or worse adverse events that occurred more frequently among patients who received bevacizumab included hypertension (27.5% vs. 9.7%; P < .001) and proteinuria (4% vs. 0%; P = .007).
“All other remaining toxic effects were in the range of what was expected,” Pignata said.
“It’s my point of view that chemotherapy and bevacizumab is a clinical option for patients already treated with bevacizumab; future analyses will provide a deeper insight into prognostic and predictive factors,” Pignata said. – by Melinda Stevens
Pignata S, et al. Abstract 5506. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Pignata reports honoraria from AstraZeneca, Merck, Pfizer, PharmaMar, Roche and Tesaro; consultant/advisory roles with AstraZeneca, Pfizer, PharmaMar, Roche and Tesaro; and research funding to his institution from AstraZeneca and Roche. Please see the abstract for all other authors’ relevant financial disclosures.