BARCELONA – (HGSC) in the phase 3 VELIA/GOG-3005 trial.
The benefit associated with the oral poly (ADP-ribose) polymerase (PARP) inhibitor was seen in all women with newly diagnosed HGSC included in the randomized, placebo-controlled trial, regardless of BRCA mutation (BRCAm) status or homologous recombination deficiency (HRD) status,, reported at the European Society for Medical Oncology Congress.
Of 1,140 patients enrolled in the international, multicenter trial, 26% had a BRCAm and 55% were HRD positive. In the intent-to-treat population, median progression-free survival (PFS) was 23.5 months in 382 patients who received carboplatin/paclitaxel (CP) plus veliparib followed by veliparib maintenance (veliparib group 1) versus 17.3 months in 375 patients treated with CP alone followed by placebo maintenance (the control group) (hazard ratio, 0.68), according to Dr. Coleman, professor and Ann Rife Cox Chair in Gynecology in the department of gynecologic oncology and reproductive medicine in the division of surgery at the University of Texas MD Anderson Cancer Center, Houston.
Among 200 patients with a deleterious BRCAm, including 108 in the veliparib 1 group and 92 in the control group, median PFS was 34.7 and 22.0 months, respectively (HR, 0.44), and among 421 patients with HRD and BRCAm, including 214 in the veliparib 1 group and 207 in the control group, median PFS was 31.9 versus 20.5 months (HR, 0.57).
In the non-HRD population of 249 patients (125 in the veliparib 1 arm and 124 in the control arm), median PFS was 15.0 and 11.5 months, respectively.
The PFS for an additional group of 383 patients treated with CP plus veliparib followed by placebo maintenance (veliparib group 2) didn’t differ significantly from either the veliparib 1 or the control group (HR, 1.07 vs. the control group in the intent-to-treat population), and the PFS rates were also similar for the BRCAm and HRD-positive patients in the veliparib 2 group and control group, he noted, explaining that the main focus of his presentation was the primary study endpoint of median PFS in the veliparib 1 versus control group.
The overall response rates at the end of treatment in the intent-to-treat populations were 84% in the veliparib 1 group, 74% in the control group, and 79% in the veliparib 2 group, Dr. Coleman said, adding that response rates were numerically higher in both veliparib-containing arms.
Additional analyses, including overall survival, will be reported at a future date, he noted.
Study participants were adults with a mean age of 62 years who had previously untreated stage III-IV HGSC. Treatment included six cycles of CP at 21-day intervals, with paclitaxel given either weekly or every 3 weeks following primary cytoreduction or neoadjuvant chemotherapy with interval cytoreduction. The veliparib dose when given with CP was 150 mg twice daily, and the veliparib maintenance dose was 400 mg twice daily for 30 cycles.
Relative CP dose intensities were similar between arms, and grade 3-4 adverse events were similar in the veliparib 1 and control groups during CP – with the exception of thrombocytopenia, which occurred in 27% and 8% of patients in the groups, respectively. During maintenance, the rates of any grade 3-4 adverse events were higher in the veliparib 1 group versus the control group (45% vs. 32%), but serious adverse event rates were similar in the groups (17% and 19%).
Observed toxicities were consistent with the known veliparib safety profile, Dr. Coleman said.
The findings are notable, as PARP inhibitors have proven effective in ovarian cancer, but their use in combination with chemotherapy has been challenging because of hematologic toxicity, he added, explaining, however, that veliparib has not only been shown to have single agent activity in germline BRCAm recurrent ovarian cancer patients, but also has binding characteristics – namely increased protein poly ADP-ribosylation and decreased PARP trapping – that could allow for its use in combination with chemotherapy.
VELIA/GOG-3005 is the first randomized trial designed to enroll only untreated patients with advanced-stage HGSC regardless of BRCA status, surgical management, or response to treatment, and the findings suggest that veliparib can be safely administered with CP and should be considered a new treatment option for women with newly diagnosed, advanced-stage serous ovarian cancer, he concluded.
In an ESMO press release,, head of the gynecologic cancer program at Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Barcelona, said that this trial, along with others such as the trial, the trial, and the trial, which each looked at integrating PARP inhibitors into first-line treatment, represents “a milestone for patients.”
“After decades studying different chemotherapy approaches, it is the first time we have meaningfully prolonged progression free survival and hopefully we will improve long-term outcome,” she said.
The study was sponsored by AbbVie. Dr. Coleman and Dr. Oaknin reported relationships with numerous pharmaceutical companies.
SOURCE: Coleman RL et al. ESMO 2019, .