Platinum-Gemcitabine-Avastin (PGA) for platinum-resistant/refractory ovarian cancer.

ABSTRACT

OBJECTIVES: Synergism between gemcitabine and platinum is known clinically. Bevacizumab in combination with single-agent chemotherapy has demonstrated significant clinical activity in platinum-resistant recurrent ovarian cancer in AURELIA study. However, the efficacy of platinum-gemcitabine-bevacizumab (PGA) has not been investigated in the platinum-resistant population. MATERIALS AND METHODS: A retrospective chart review was conducted in all patients with platinum-resistant/refractory ovarian cancer treated with triplet combination therapy containing a platinum agent, gemcitabine, and bevacizumab between July 2011 and December 2013. RESULTS: In total, 13 patients met the selection criteria, including ten patients with resistant disease (10/13, 77%) and three patients with refractory disease (3/13, 23%). Most of the patients were heavily pre-treated, having received over three lines of prior chemotherapy regimens on average (range 1-11). All patients had previously received taxane therapy; four patients received gemcitabine, seven patients failed combination regimens including bevacizumab, and three patients progressed on chemotherapy including both gemcitabine and bevacizumab. Ten patients responded biochemically to the therapy (defined by CA-125 declined by at least 50%). Of ten responders, one patient achieved CR for 24 months (8%), six patients achieved PR for 6.8 months (46%), three had stable disease for 6.7 months (23%), and three patients had PD (23%) by RECIST 1.1 criteria. The regimen was well-tolerated. One patient (8%) developed grade 3 neutropenia and neutropenic fever, requiring hospitalization, two patients developed grade 3 thrombocytopenia, two patients (15%) developed thrombosis in internal jugular vein, requiring discontinuation of bevacizumab, one patient (8%) experienced skin ulcer, and two patients developed thrombosis in internal jugular vein, requiring discontinuation of bevacizumab. CONCLUSIONS: Combination of PGA appears to be safe and very active against platinum-resistant/refractory ovarian cancer and merits further evaluation prospectively. A randomized phase II study (NCTO 1936974) is currently under way to confirm this important finding.