Carboplatin/Pegylated Liposomal Doxorubicin/Bevacizumab vs Carboplatin/Gemcitabine/Bevacizumab in Patients with Recurrent Ovarian Cancer
For patients with recurrent ovarian cancer suitable for platinum-based retreatment, standard platinum-containing treatments include carboplatin/gemcitabine/bevacizumab (CG-BEV) and carboplatin/pegylated liposomal doxorubicin (CD). CG-BEV has been shown to significantly increase progression-free survival (PFS) over CG alone,1 whereas CD has one of the best therapeutic indices for platinum-sensitive recurrent ovarian cancer that is suitable for retreatment.2 Here, Pfisterer et al report the results of a prospective, randomized, phase 3 trial, designed to evaluate whether CD is superior to CG when given in combination with BEV with investigator-determined PFS as the primary objective.3
Patients with recurrent ovarian cancer suitable for platinum-based retreatment were randomized to receive standard CG-BEV (nâ€‰=â€‰337) or experimental CD-BEV (nâ€‰=â€‰345). Secondary objectives included overall survival, biological PFS by serum CA125 levels, quality of life, safety, and tolerability. The trial was designed to have 80% power to show a 26.6% change in PFS (hazard ratio [HR], 0.79; 564 PFS events). Patients were stratified by presence of residual tumor, platinum-free interval, and prior antiangiogenic treatment.
At the time of data cutoff, 571 events had occurred. Of the included patients, 87.4% had serous histology, 83.1% were high grade, and 41.5% had previously received BEV as part of first-line treatment. CG-BEV was associated with 359 (53.3%) serious adverse events versus 314 (46.7%) for CD-BEV (Pâ€‰=â€‰.083). Median PFS in the CG-BEV arm was 11.7 months (95% CI [confidence interval], 11.1-12.8) versus 13.3 months (95% CI, 11.7-14.3) in the experimental CD-BEV arm (HR, 0.80; 95% CI, 0.68-0.96; P =â€‰.0128). For patients who had received previous antiangiogenic treatment (nâ€‰=â€‰309), median PFS was 10.1 months (95% CI, 8.5-11.2) for CG-BEV versus 11.3 months (95% CI, 10.1-13.8) for CD-BEV (HR, 0.73; 95% CI, 0.57-0.94; Pâ€‰=â€‰.0126).
Experimental CD-BEV provided a significant PFS improvement compared with CG-BEV in patients with recurrent ovarian cancer suitable for platinum-based retreatment. A significant PFS improvement was also seen in the subgroup of patients who had received previous antiangiogenic treatment. Furthermore, CD-BEV was associated with fewer serious adverse events, including a 45% reduction in grade ≥3 neutropenia. These data suggest that CD-BEV could be an important addition to the therapeutic options in these patients.
- Aghajanian C, et al. J Clin Oncol. 2012;30(17):2039-2045.
- Mahner S, et al. Eur J Cancer. 2015;51(3):352-358.
- Pfisterer J, et al. ESMO 2018. Abstract 933O.