Veliparib continues to show positive signals in ovarian cancer
Subgroup analyses of the VELIA* trial showed that the concomitant administration of the poly(adenosine diphosphate-ribose) polymerase inhibitor veliparib with an induction chemotherapy (CT) regimen comprising carboplatin and paclitaxel (CP) generated antitumour activity and favourable safety in women with high-grade serous ovarian cancer.
VELIA included 1,140 women (median age 62 years) with previously untreated advanced-stage (stage III/IV) ovarian cancer. Six cycles (21 days/cycle) of CP** were administered after primary cytoreductive surgery or as neoadjuvant CT with interval cytoreduction. Participants were randomized 1:1:1 to receive CP + veliparib 150 mg BID (combination phase) followed by a 30-cycle maintenance phase (cycle 7 onwards) with veliparib (veliparib throughout***) or placebo (veliparib combo), or CP + placebo followed by placebo maintenance (control arm).
In the exploratory analyses evaluating responses during the combination phase, there were more veliparib than placebo recipients who achieved a CA-125# response (ie, ≥90-percent reduction from baseline) by cycle 3 (37/31 percent [veliparib throughout/combo] vs 23 percent [placebo]). A similar trend in CA-125 response was observed among patients undergoing neoadjuvant CT (57/46 percent vs 37 percent). [SGO 2020, abstract LBA 9]
In participants with measurable disease following primary surgery, there were more veliparib recipients who had a complete response (CR) compared with the control arm (26/23 percent vs 18 percent).
“[These results show that] veliparib added to frontline CP during induction resulted in a modest increase in CA-125 responses and CRs in [this patient setting]. These … suggest that veliparib + CP during combination phase may provide antitumour activity [over] CP alone,” said the researchers. These results support the efficacy findings (ie, progression-free survival advantage favouring veliparib) initially established in VELIA. [N Engl J Med 2019;381:2403-2415]
Patients with BRCA mutations (BRCAm) or homologous recombination-deficient (HRD) tumours may be more susceptible to treatment-related toxicities. Thus, another subanalysis evaluated adverse events (AEs) among participants in the veliparib-throughout arm (n=377). [SGO 2020, abstract LBA 37]
During the combination and maintenance phases, the most common grade 3/4 haematologic AEs were neutropenia and anaemia. The rates of these AEs were comparable between the overall cohort and the BRCAm/HRD tumour subgroups (58 percent vs 63/61 percent [neutropenia] and 38 percent vs 37/38 percent [anaemia]). The AE rates leading to dose reduction were also comparable (24 percent vs 24/26 percent). Grade 2–4 nonhaematologic AEs were predominantly gastrointestinal (eg, nausea, vomiting, diarrhoea, and constipation).
“[This subanalysis shows that the AE] frequencies were generally similar among the whole patient population and biomarker-positive patient subsets … [Moreover, the overall] prevalence of all-grade neutropenia, anaemia, thrombocytopenia, and nausea decreased substantially from cycles 7 [through] 12,” said the researchers.
These safety findings correlate with the safety profile of veliparib established in the initial results of VELIA, noted the researchers. Moreover, the current toxicity results reinforce evidence confirming the safety of veliparib when administered concurrently with standard CT. [J Clin Oncol 2019;37:5523]