Rucaparib Maintenance Extends Survival
Madrid, Spain—Maintenance therapy with the poly ADP-ribose polymerase (PARP) inhibitor rucaparib (Rubraca) after response to platinum-containing therapy significantly improved progression-free survival (PFS) by 11.2 months in patients with recurrent ovarian cancer compared with placebo, according to overall results of the ARIEL3 trial. The study was presented at the 2017 European Society for Medical Oncology (ESMO) Congress.
The PFS was significantly longer with rucaparib versus placebo in patients with ovarian cancer and a germline or somatic BRCA mutation, those with a BRCA mutation or with BRCA wild-type who had homologous recombination deficiency (HRD), and all patients included in the study (intent-to-treat population).
“These results reinforce the potential of rucaparib to provide an enduring and significant clinical benefit in women with advanced ovarian cancer, regardless of their tumor genetics,” said lead investigator Jonathan A. Ledermann, MD, FRCP, Deputy Director and Clinical Lead, UCL Cancer Institute, London, England, who presented the study results.
“It is both impressive and encouraging that rucaparib demonstrated improvements in key primary, secondary, and exploratory end points in all 3 ARIEL3 populations. It is also clinically significant that rucaparib not only sustained patients’ most recent responses to platinum, but in some participants also enhanced that response, including the radiological elimination of residual tumor,” Dr Ledermann added.
The ARIEL3 clinical trial was a double-blind, placebo-controlled phase 3 study of 564 women with 1 of 3 types of cancer—platinum-sensitive, high-grade ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Patients were randomized to receive rucaparib maintenance therapy or placebo.
Rucaparib reduced the risk for disease progression by 77% in patients with a BRCA mutation (N = 196). According to investigator assessment, the median PFS in this group was 16.6 months for rucaparib versus 5.4 months for placebo (P <.0001). In the HRD subpopulation (N = 354), the median PFS was 13.6 months with rucaparib versus 5.4 months with placebo (P <.0001). In the overall intent-to-treat analysis (N = 564), rucaparib reduced the risk for disease progression by 64% (median PFS, 10.8 months vs 5.4 months; P <.0001).
In an exploratory PFS analysis in patients with BRCA wild-type ovarian cancer and high or low loss of heterogeneity (LOH) disease (N = 158 and N = 161, respectively), rucaparib significantly improved median PFS for both subgroups. The LOH test failed to separate responders from nonresponders.
The most common grade ≥3 treatment-emergent adverse events with rucaparib were anemia/decreased hemoglobin (19%), increase in ALT/AST (10%), neutropenia (7%), asthenia/fatigue (7%), thrombocytopenia (5%), vomiting (4%), and nausea (4%). Discontinuations because of treatment-emergent adverse events were 13.4% with rucaparib and 1.6% with placebo.
Commenting on the study, Andrés Poveda, MD, Head of the Gynaecological Cancer Clinic, Oncology Foundation Institute Valencia, Spain, said, “ARIEL3 achieved a huge decrease in the risk of relapse with rucaparib. All of the patient subgroups benefitted, especially those with BRCA mutations but also homologous recombination deficient (HRD) patients.”
“Further studies are needed to identify biomarkers of response to PARP inhibitors, specifically, whether there are non-HRD factors that predict response,” Dr Poveda added.
Sandro Pignata, MD, PhD, Uro-Gynecological Department, National Cancer Institute of Naples, Italy, said, “This is new evidence for maintenance therapy with rucaparib. These results are extraordinary, particularly in the BRCA mutation patients, but also in the BRCA wild-type and high LOH subgroups. But rucaparib was also effective even if we consider the whole population.”
“Rucaparib is another option for maintenance therapy. The 3 PARP inhibitors have some differences in toxicity, and we will need to consider safety profile in treatment selection,” Dr Pignata said.