Experimental regimen prolongs PFS in recurrent ovarian cancer

MUNICH — Women with recurrent ovarian cancer treated with carboplatin, pegylated liposomal doxorubicin and bevacizumab achieved longer PFS than those who received standard treatment with carboplatin, gemcitabine and bevacizumab, according to randomized phase 3 study results presented at European Society for Medical Oncology Congress.

Perspective from Sandro Pignata, MD

The novel combination also appeared safe.

“Carboplatin plus pegylated liposomal doxorubicin in combination with bevacizumab is a new treatment option for patients with recurrent ovarian cancer suitable for platinum-based retreatment, even after previous antiangiogenic treatment,” Jacobus Pfisterer, MD, PhD, professor of medicine at Städtisches Klinikum Solingen in Germany, said during a presentation.

Standard therapy for women with recurrent ovarian cancer suitable for platinum-based retreatment consists of carboplatin, gemcitabine and bevacizumab (Avastin; Genentech, Biogen), or carboplatin plus pegylated liposomal doxorubicin.

In the prospective ENGOT/GCIG-Intergroup study, Pfisterer and colleagues assessed whether the carboplatin-pegylated liposomal doxorubicin or carboplatin-gemcitabine proved more efficacious when combined with bevacizumab.

The analysis included 682 women (mean age, 62 years) with recurrent ovarian cancer suitable for platinum-based retreatment.

Most women had serous histology (87.4%), high-grade tumors (83.1%) and ECOG performance status of 0 (62%). Fewer than half (41.5%) had received bevacizumab as part of first-line treatment.

Researchers randomly assigned 345 women to the experimental regimen, administered in six 4-week cycles. Treatment consisted of bevacizumab 10 mg/kg every 2 weeks, plus pegylated liposomal doxorubicin 30 mg/m² and carboplatin area under the curve (AUC) 5 on day 1 of each cycle. Bevacizumab treatment continued at 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

The other 337 patients received a standard regimen administered in six 3-week cycles. It consisted of bevacizumab 15 mg/kg every 3 weeks, plus gemcitabine 1,000 mg/m2 on days 1 and 8, and carboplatin AUC 4 on day 1. Bevacizumab treatment continued at 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

Investigator-determined PFS served as the primary endpoint. Secondary endpoints included biological PFS by serum cancer antigen 125, OS, quality of life assessed by the EORTC-QLQ-C30 and QLQ-OV28 scales, safety and tolerability.

Researchers observed 571 PFS events at the time of data cutoff.

Patients assigned the experimental regimen achieved significantly longer median PFS (13.3 months vs. 11.7 months; HR = 0.8; 95% CI, 0.68-0.95). They also achieved longer median OS, but the difference did not reach statistical significance (33.5 months vs. 28.2 months; HR = 0.83; 95% CI, 0.68-1.02).

When researchers analyzed outcomes among the 309 patients who underwent prior antiangiogenic treatment, they determined the experimental regimen conferred a significant PFS benefit (median, 11.5 months vs. 10 months; HR = 0.73; 95% CI, 0.57-0.94).

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Global quality of life was superior in the experimental group (P < .05).

No new safety signals emerged with the experimental regimen, Pfisterer said. Researchers reported no significant difference in the rate of serious adverse events in the experimental group and standard treatment group (46.7% vs. 53.3%).

“[Carboplatin, pegylated liposomal doxorubicin and bevacizumab] provided a significant PFS improvement compared [with carboplatin, gemcitabine and bevacizumab for] patients with recurrent ovarian cancer suitable for platinum-based retreatment,” Pfisterer and colleagues wrote. “A significant PFS improvement was also seen in the subgroup of patients with previous antiangiogenic treatment. [The experimental regimen] was associated with fewer serious adverse events. Thus, [it] might be an important addition to the therapeutic options [for] these patients.” – by Jennifer Southall

Reference:

Pfisterer J, et al. Abstract 933O. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.

Disclosures: F. Hoffman-La Roche provided funding for this study. Pfisterer reports consultant/advisory roles with, research funding from and travel accommodations/expenses from Roche. Please see the abstract for all other authors’ relevant financial disclosures.

Perspective

Sandro Pignata, MD

Treatment for recurrent ovarian cancer is one of the major tasks for us in clinical practice. Traditionally, we select patients for new treatment according to platinum-based retreatment. Patients who are platinum resistant have very poor outcomes. The majority of improvements have been observed in sensitive disease due to new treatment schedules and with the addition of bevacizumab.

This study shows very strong evidence that carboplatin plus pegylated liposomal doxorubicin and bevacizumab is better than carboplatin plus gemcitabine and bevacizumab. This study also confirms that bevacizumab after first-line bevacizumab is safe.

The question becomes: What else do we need now? We need a new label. We ought to be able to use carboplatin plus pegylated liposomal doxorubicin and bevacizumab in our practices.

Sandro Pignata, MD

IRCCS National Cancer Institute Fondazione G. PascaleNaples, Italy

Disclosures: Pignata reports honoraria from AstraZeneca, Clovis, GenMab, Merck Sharpe & Dohme, Pfizer, PharmaMar, Roche and Tesaro; and research funding from AstraZeneca and Roche.