Second-line treatment with a combination of bevacizumab plus the chemotherapies carboplatin and pegylated liposomal doxorubicin may significantly improve the outcomes of platinum-sensitive ovarian cancer patients, compared to standard treatment, findings from a Phase 3 trial suggest.
Women who received this experimental combination in the ENGOT-ov18 trial (NCT01837251) lived significantly longer without disease progression and experienced extended overall survival than those on standard bevacizumab, carboplatin, and gemcitabine, all without impairing quality of life.
The findings were detailed in a study, “Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial,” published in The Lancet Oncology.
Current treatment for women with ovarian cancer who responded to first-line platinum-based chemotherapy consists of a combination of bevacizumab, a therapy marketed as Avastin by Roche, among other brand names, that prevents blood vessels from growing in cancers, plus the chemotherapeutic agents carboplatin (marketed as Paraplatin, among others), and gemcitabine (sold as Gemzar and other names).
Research suggests that replacing gemcitabine in that combination for a liposomal formulation of doxorubicin (brand names Caelyx or Doxil) may further improve the outcomes of these women. But so far no randomized trials have directly compared these two regimens.
The multi-center ENGOT-ov18 trial, funded by Roche, included 682 patients with epithelial ovarian, primary peritoneal, or fallopian tube carcinoma whose disease had progressed more than six months after first-line platinum-based chemotherapy.
Participants, enrolled at 159 academic centers in Europe and Australia, were randomly assigned to receive bevacizumab, carboplatin, and gemcitabine in three-week cycles or bevacizumab, carboplatin, and pegylated liposomal doxorubicin in four-week cycles.
Treatment was given for up to six cycles, followed by maintenance with bevacizumab, administered every three weeks until disease progression or unacceptable signs of toxicity.
The trial’s main goal was to determine if the liposomal doxorubicin-containing regimen significantly extended the time without disease progression or death. Secondary measures included overall survival, quality of life, safety, and tolerability.
At the time of the analysis, patients in the experimental arm had been followed for a median of 12.4 months and those on standard treatment for a median of 11.3 months. At that time, about 80% and 87% of patients in each group had either died or experienced disease worsening.
Researchers found that the liposomal doxorubicin-containing regimen significantly extended survival without disease progression by a median of 1.7 months — to 13.3 months compared with 11.6 months on standard treatment. Survival time was also longer with this regimen (median 31.9 months) compared with the gemcitabine triple combo (27.8 months).
The findings meant that the experimental treatment reduced both risk of death and of disease progression or death by 19%, a reduction that was maintained even after excluding data from the 84 patients who received bevacizumab after disease progression.
During the study, patients in both groups experienced similar reductions in their quality of life.
Overall, most patients in both groups experienced at least one adverse event, but those on the gemcitabine regimen more frequently experienced severe or worse side effects (81%) than those on liposomal doxorubicin (75%).
Nevertheless, researchers said that the “safety profile in both treatment groups was consistent with the known side-effects of bevacizumab and the chemotherapy backbones.”
While the results suggest that the triple combination containing pegylated liposomal doxorubicin should be a “new standard regimen for patients with recurrent ovarian cancer,” the researchers warn that this trial was designed in 2012, before PARP inhibitors became the standard of care for recurrent platinum-sensitive ovarian cancer, which is a clear limitation.
As “PARP inhibitors are used earlier in the treatment algorithm, the patient population enrolled in [ENGOT-ov18] might become less representative of patients presenting in clinical practice in the future,” they wrote.
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