Upfront Maintenance Combination for Advanced Ovarian Cancer Not Ready for Clinical Use

Amina Ahmed, MD, Associate Chief Medical Officer, Gynecology, Cancer Center of Rush University Medical Center, Chicago, IL; Paula Anastasia, RN, MN, AOCN, Clinical Nurse Specialist, Gynecologic Oncology, University of California Los Angeles Health; and Ali McBride, PharmD, MS, Clinical Coordinator, University of Arizona Cancer Center, Tucson, discussed the benefits and risks of using combination therapy with a poly (ADP-ribose) polymerase (PARP) inhibitor and bevacizumab (Avastin) as first-line maintenance therapy in patients with ovarian cancer.

“I wouldn’t [use a combination] in general [as maintenance treatment] because there is additive toxicity and it’s hard to know if the combination of bevacizumab and a PARP inhibitor is superior over PARP inhibitor alone,” said Dr Ahmed. “I think, in general, practitioners are probably a little leery of adding two agents for maintenance.”

The PAOLA-1 clinical trial found a progression-free survival (PFS) of 22.1 months with the combination of olaparib (Lynparza) and bevacizumab, compared with 16.6 months for placebo and bevacizumab in patients who had received first-line therapy for advanced ovarian cancer, including bevacizumab, but the trial was lacking an olaparib-alone arm.

In patients with a tumor BRCA mutation, median PFS was 37.2 months in the olaparib group and 21.7 months in the placebo group. The hazard ratio for PFS was 0.33 (95% confidence interval [CI], 0.25-0.45) in patients with tumors positive for homologous recombination deficiency (HRD), including tumors that had BRCA mutations (median PFS, 37.2 vs 17.7 months), and 0.43 (95% CI, 0.28-0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median PFS, 28.1 vs 16.6 months). 

The PAOLA-1 study investigators admitted to the lack of a maintenance monotherapy comparator group as a limitation of PAOLA-1, “making it difficult to conclude whether the PFS benefit seen in patients with HRD-positive tumors without BRCA mutations…was due largely to the addition of olaparib or whether a synergistic effect occurred with olaparib and bevacizumab.”

“We’re still just waiting and treading because we also know that bevacizumab works really well in the recurrent setting,” said Ms Anastasia. “Obviously our goal is to delay or prevent a recurrent setting. But I think we’re just tiptoeing because we don’t want to waste a drug that may have better use in a recurrent setting.”

In agreement was Dr McBride, who said that a drug used as additive therapy would be lost as a potential sequential therapy when one is needed, and the number of therapies in this indication is limited.