In the phase III VELIA trial, the addition of veliparib to frontline induction chemotherapy expanded the number of complete responses and CA-125 responses in patients with high-grade serous ovarian cancer compared with chemotherapy alone, according to results from an exploratory analysis.
David O'Malley, MD
In the phase III VELIA trial, the addition of veliparib to frontline induction chemotherapy expanded the number of complete responses (CRs) and CA-125 responses in patients with high-grade serous ovarian cancer compared with chemotherapy alone, according to results from an exploratory analysis.1
The 3-arm VELIA trial randomized patients to veliparib plus induction carboplatin and paclitaxel (CP) either with (veliparib throughout) or without veliparib maintenance, or a control arm of induction CP with no maintenance. The overall study results showed a significant progression-free survival (PFS) benefit for the veliparib throughout arm versus the control arm. However, a similar benefit was not demonstrated in the veliparib arm that did include maintenance therapy. Thus, this exploratory analysis was conducted to try to isolate the benefit of veliparib during the CP plus veliparib combination phase.
Among the veliparib-throughout arm, the CR rate during the combination phase was 26% (25 of 98). During this phase, the CR rate was 23% (23 of 99) in the cohort receiving veliparib in the combination phase only (combo only), and the CR rate was 18% (17 of 93) in the control arm. The CA-125 response by cycle 3 was 37% (118 of 316 evaluable patients) in the veliparib throughout arm, 31% (100 of 323) in the combo-only arm, and 23% (76 of 324) in the control arm.
Specifically among patients receiving neoadjuvant chemotherapy, the CA-125 response during the combination phase was 57% (49 of 86 evaluable patients) in the veliparib throughout arm, 46% (46 of 101) in the combo-only arm, and 37% (37 of 100) in the control arm. The rates of stable disease were 8%, 9%, and 19% in the 3 arms, respectively.
The findings from the study were made available as part of the virtual platform for the SGO 2020 Annual Meeting that was implemented due to the shutdown caused by the novel coronavirus (COVID-19).
“These exploratory analyses suggest that veliparib added to CP during the combination phase may provide antitumor activity above CP alone,” lead study investigator David M. O’Malley, MD, professor, Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, and director, Division of Gynecologic Oncology at The Ohio State University Comprehensive Cancer CenterThe James, and coauthors wrote. Overall, 1140 patients underwent randomization in the VELIA trial. The control arm consisted of carboplatin and paclitaxel with placebo followed by placebo as maintenance (n = 375). In the veliparib throughout arm, the PARP inhibitor was added at 150 mg twice daily to carboplatin and paclitaxel followed by veliparib alone at 400 mg twice daily as maintenance (n = 382). The combo-only arm examined the addition of veliparib at 150 mg twice daily to carboplatin and paclitaxel as induction therapy followed by placebo maintenance (n = 383). CP was administered over 6 cycles (21-day interval) following primary cytoreduction or as neoadjuvant chemotherapy with interval cytoreduction.
Patient characteristics were well balanced across arms. The median age of patients was 62 years, and approximately 60% had an ECOG performance status of 0. Two-thirds of patients had stage III disease, and most had received primary surgery, with the remaining having interval surgery. Nearly half of patients in both groups had no residual disease, and approximately 30% had residual disease.
In the veliparib-throughout arm, the median PFS for the induction and maintenance phases combined was 23.5 months compared with 17.3 months in the control arm (HR, 0.68; 95% CI, 0.56-0.83;P<.001).1,2The benefit was more pronounced for those with BRCAmutations. In this group, the median PFS was 34.7 months compared with 22.0 months for veliparib and placebo, respectively (HR, 0.44; 95% CI, 0.28-0.68; P<.001).
In those testing positive for homologous recombination deficiency (HRD), the median PFS was 31.9 months in those receiving veliparib throughout the trial compared with 20.5 months in the control arm (HR, 0.57; 95% CI, 0.43-0.76;P<.001). Data were not yet sufficiently mature to conduct overall survival analyses across the groups.
In those receiving veliparib with induction chemotherapy followed by placebo maintenance, the median PFS across the full study was 15.2 months compared with 17.3 months in the control arm (HR, 1.07; 95% CI, 0.90-1.29). In the BRCA group, the median PFS was 21.1 months with this regimen compared with 22.0 months for the control (HR, 1.22; 95% CI, 0.82-1.80). In the HRD-positive group, the median PFS was 18.1 months with the combination compared with 20.5 months for the control (HR, 1.10; 95% CI, 0.86-1.41).
An objective response rate (ORR) was available for patients with measurable disease at study entry (25% of study). Those receiving veliparib throughout the full study had an ORR of 84% compared with 79% and 74% in the veliparib upfront alone and control arms, respectively.
An assessment of PFS prior to beginning maintenance therapy revealed some data on the efficacy of adding veliparib to the frontline therapy. In this analysis, PFS was not improved with the combination of veliparib and chemotherapy versus the control group (HR, 1.07; 95% CI, 0.90-1.29). These findings were consistent across subgroups.
At least 1 treatment-emergent adverse event (AE) was experienced by all patients across the 3 arms. Grade 3/4 AEs were experienced by 88% of those receiving veliparib throughout and for 88% of those receiving veliparib only in the induction combination. In the control arm, grade 3/4 AEs were experienced by 77% of patients.
The most commonly observed grade 3/4 AEs in the veliparib throughout group compared with control, respectively, were neutropenia (58% vs 49%), anemia (38% vs 26%), thrombocytopenia (28% vs 8%), and leukopenia (18% vs 9%). In the veliparib induction/placebo maintenance group, the most common grade 3/4 AEs were neutropenia (62%), anemia (41%), thrombocytopenia (31%), and leukopenia (12%).