Sandro Pignata, MD

The study’s invited discussant, Sandro Pignata, MD, of the Istituto Nazionale Tumori di Napoli in Italy, called the data from AGO OVAR 2.21 “very strong.” He added: “We now have robust evidence from a trial of more than 600 patients, in which previous bevacizumab (Avastin) was allowed, that carboplatin, pegylated liposomal doxorubicin, and bevacizumab is better than carboplatin, gemcitabine, and bevacizumab…. The study confirmed that bevacizumab after bevacizumab is safe. We can treat patients again with bevacizumab after the first line.”

Although patients with recurrent disease are primarily selected for retreatment according to their platinum-free interval, this is not the only parameter that should be considered in choosing treatment. Tumor biology and histology are clearly important, especially the presence of BRCA mutations and homologous recombination defect, he emphasized.

“BRCA and homologous recombination defect status were missing from this trial. BRCA status has a significant prognostic role, platinum-sensitive recurrence is enriched for homologous recombination defect–deficient patients, and carboplatin/pegylated liposomal doxorubicin may be more effective in these patients,” he said. Dr. Pignata explained that pegylated liposomal doxorubicin has a mechanism of action that makes it especially effective in this subgroup and also demonstrates immunomodulatory effects that are amplified in BRCA1-deficient tumors.

New combinations and strategies need to be investigated for their innovative effects, he added, and BRCA and homologous recombination defect should be explored as possible biomarkers for tailoring treatments. ■

DISCLOSURE: Dr. Pignata has received honoraria from AstraZeneca, Roche, PharmaMar, Tesaro, Pfizer, and MSD; is a consultant/advisor for Pfizer, Tesaro, -AstraZeneca, Roche, and PharmaMar; and has received institutional research funding from Roche and AstraZeneca.