Safety of veliparib in combination with chemotherapy and as maintenance in front-line ovarian cancer: Results in BRCAm, hrd, and whole populations from the velia trial: Webinar #4: Molecular testing and patient selection in ovarian cancer How Do We Optimize PROs? ORAL abstract

Elizabeth M Swisher, Robert L Coleman, Michael A Bookman, M.F. Brady, Gini F Fleming, Michael Friedlander, J. Cunningham, K.S. Tewari, B Edraki, G.M. Mantia-Smaldone, C. K. Ratajczak, Minh H Dinh, Danielle M Sullivan, S McClain, S Okubo, Karina Dahl Steffensen, Carol Aghajanian

Research output: Contribution to conference without publisher/journalConference abstract for conferenceResearchpeer-review

Abstract

Objective:
The phase 3 VELIA trial demonstrated that veliparib dosed concurrently with carboplatin/paclitaxel and continued as maintenance monotherapy resulted in a statistically significant improvement in progression-free survival compared to carboplatin/paclitaxe alone in patients with newly diagnosed stage III–IV high-grade serous ovarian, fallopian tube, and peritoneal cancer. It has been hypothesized that while DNA repair deficiencies may improve response to PARP inhibition, they may also render patients with BRCA mutations (BRCAm) or homologous recombination-deficient (HRD) tumors more sensitive to treatment-related toxicities.

Method:
Patients were eligible regardless of biomarker status and were randomized to 1 of 3 treatment arms. This analysis is limited to patients randomized to carboplatin/paclitaxel plus veliparib followed by veliparib maintenance. Patients received 6 cycles (21 days/cycle) of carboplatin (AUC 6) and paclitaxel (175 mg/m2 q3w or 80 mg/m2 weekly). Veliparib was continuously dosed at 150 mg BID PO with carboplatin/paclitaxel and then at 300 mg BID, increasing to 400 mg BID if tolerated, for 30 additional cycles. Patients receiving ≥1 dose of study drug were included in safety analyses. Adverse events in patients randomized to carboplatin/paclitaxel plus veliparib followed by veliparib maintenance are reported for the whole patient population, as well as for the BRCAm and HRD patient subsets.

Results:
During the entire treatment period (combination chemotherapy and maintenance), grade 2–4 nonhematologic adverse events were predominantly gastrointestinal. Grade 3–4 hematologic adverse events included neutropenia and anemia in more than one-third of patients. Frequency of common adverse events was generally comparable in the whole population and the BRCAm and HRD patient subsets. Frequency of adverse events leading to dose reduction was also comparable. In the whole population, the prevalence of all-grade neutropenia, anemia, thrombocytopenia, and nausea decreased substantially from cycles 7–9 to cycles 10–12 (in which cycle 7 was the first cycle of monotherapy maintenance). See Table 1.

Conclusion:
In VELIA, adverse event frequencies were generally similar among the whole patient population and biomarker-positive patient subsets.
Table 1. Common treatment-emergent AEs during entire treatment period (combination and maintenance) in patients randomized to veliparib in combination with C/P and continued as maintenance monotherapy.


Table: Adverse event, n (%)
Whole Population
(n = 377)
BRCAm Population
(n = 106)
HRD Population
(n = 211)
AE leading to dose reduction
89 (23.6)
26 (24.5)
55 (26.1)
Hematologic AEs (Grade 3-4)
Neutropenia
218 (57.8)
67 (63.2)
129 (61.1)
Anemia
144 (38.2)
39 (36.8)
80 (37.9)
Thrombocytopenia
105 (27.9)
27 (25.5)
56 (26.5)
Leukopenia
66 (17.5)
18 (17.0)
38 (18.0)
Non-hematologic AEs (Grade 2-4)
Nausea
167 (44.3)
46 (43.4)
100 (47.4)
Fatigue
137 (36.3)
44 (41.5)
73 (34.6)
Alopecia
126 (33.4)
37 (34.9)
75 (35.5)
Vomiting
70 (18.6)
19 (17.9)
40 (19.0)
Peripheral sensory neuropathy
63 (16.7)
17 (16.0)
37 (17.5)
Urinary tract infection
61 (16.2)
16 (15.1)
32 (15.2)
Diarrhea
58 (15.4)
27 (25.5)
37 (17.5)
Constipation
47 (12.5)
17 (16.0)
30 (14.2)
Original languageEnglish
Publication date7. May 2020
Publication statusPublished - 7. May 2020
EventSGO Annual Meeting of Women's Cancer: Converted to webinar due to COVID-19 restrictions - Toronto, Canada
Duration: 28. Mar 202031. Mar 2020
https://www.sgo.org/education/annual-meeting-on-womens-cancer/

Conference

ConferenceSGO Annual Meeting of Women's Cancer
CountryCanada
CityToronto
Period28/03/202031/03/2020
Internet address

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