medwireNews: The VELIA/GOG-3005 trial results support the use of veliparib in combination with carboplatin and paclitaxel for the first-line treatment of stage III–IV, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, followed by maintenance therapy with the PARP inhibitor.
The phase III findings were published in The New England Journal of Medicine to coincide with a presentation at the ESMO 2019 Congress in Barcelona, Spain, by lead investigator Robert Coleman, from the University of Texas MD Anderson Cancer Center in Houston, USA.
The trial recruited 1140 participants.Patients were randomly assigned to receive veliparib 150 mg twice daily alongside six 21-day cycles of carboplatin to area under the curve of 6 mg/mL per min every 3 weeks plus paclitaxel given at a dose of 175 mg/m2 every 3 weeks or 80 mg/m2 weekly, followed by 30 cycles of veliparib maintenance; or to receive chemotherapy plus placebo, followed by placebo maintenance; or to receive chemotherapy plus veliparib followed by placebo maintenance.
For the subgroup of 297 patients with a BRCA1/2 mutation, median progression-free survival (PFS) was 34.7 months for those given chemotherapy plus veliparib, followed by veliparib maintenance, and this was significantly longer than the 22.0 months for those patients who instead received chemotherapy plus placebo and placebo maintenance, with a HR for death or progression of 0.44 in favour of the PARP inhibitor.
The PFS benefit with veliparib throughout over placebo was also found for the 627 patients with homologous recombination deficiency (HRD)-positive disease, including those with BRCA1/2 mutations, at 31.9 versus 20.5 months and a HR of 0.57.
And veliparib combination and maintenance therapy continued to offer a significant PFS benefit within the intention-to-treat population, including all patients regardless of BRCA and HRD status, at 23.5 months with and 17.3 months without veliparib use, with a HR of 0.68.
However, the investigators say that “[t]he independent value of adding veliparib during induction therapy without veliparib maintenance was less clear”.
Analysis of the 383 patients who received veliparib during chemotherapy but placebo during maintenance gave a median PFS of 21.1 months for the BRCA1/2 mutation subgroup (HR=1.22 vs placebo), 18.1 months for the HRD subgroup (HR=1.10 vs placebo), and 15.2 months for the intention-to-treat population (HR=1.07).
“Inferences drawn from the absence of improvement in progression-free survival in the veliparib-combination-only group may suggest that the benefit from veliparib is related to its use as maintenance therapy”, the authors hypothesize, but admit the study design does not test this hypothesis.
At the time of analysis, the overall survival data for the study cohorts were not mature, they add.
Robert Coleman and team report comparable rates of adverse events (AEs) in the intention-to-treat analysis of patients given veliparib throughout versus placebo, but note the PARP inhibitor used throughout treatment was associated with greater gastrointestinal toxicity and higher rates of grade 3–4 thrombocytopenia (28 vs 8%) and anaemia (38 vs 26%).
Nevertheless, the researchers highlight that these haematological events “were significantly lower during the maintenance phase, in which less than 8% of the patients in the veliparib-throughout group had a grade 3 or 4 event.”
“In general, the incidence of toxic effects with veliparib monotherapy was lower than has been reported with other PARP inhibitors,” they add.
Coleman RL, Fleming GF, Brady MF, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer.N Engl J Med; Advance online publication 28 September 2019.DOI: 10.1056/NEJMoa1909707
Coleman RL, Fleming GF, Brady MF, et al. VELIA/GOG-3005: Integration of veliparib (V) with front-line chemotherapy and maintenance in women with high-grade serous carcinoma of ovarian, fallopian tube, or primary peritoneal origin (HGSC).ESMO 2019 Congress; Barcelona, Spain: 27 September–1 October.LBA3
medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group