Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada
Pierre Chabot , Jeong-Seon Ryu , Vera Gorbunova , Cristobal Belda , David Ball , Ebenezer A. Kio , Minesh Mehta , Katherine Papp , Qin Qin , Jane Qian , Kyle D. Holen , Vincent L. Giranda , John H. Suh
Background: Veliparib (V) is a potent, orally bioavailable PARP inhibitor that crosses the blood brain barrier. Phase 2 trials in BRCA pts as monotherapy or in unselected pts in combination with platinum-based chemotherapy have demonstrated evidence of efficacy. V plus radiation has shown promising efficacy in preclinical models and clinically in combination with WBRT. Methods: Pts were randomized 1:1:1 to WBRT plus V 50 mg BID (V50), V 200 mg BID (V200), or P BID. Treatment began within 28 days (d) of diagnosis. Pts received 30 Gray WBRT in 10 fractions. V50, V200, or P BID was self-administered starting on d 1 of WBRT and continuing until 1 d after completion. The primary endpoint was overall survival (OS). Survival was assessed at 2 month (m) intervals for 6 m then every 3 m (≥36 m). Pts who received ≥1 dose were included in the safety analyses; AEs were compared across arms using Fisher’s exact test. Results: 307 pts were randomized. OS, intracranial response rate, and time to clinical or radiographic progression were not statistically significantly different between any of the V arms and the P arm. There were no differences in all grade adverse drug reactions (ADRs) across arms and a modest improvement in grade 3/4 AEs in the V arms. Conclusions: Although preclinical and early clinical data suggested that V might synergize with radiotherapy, there was no difference in multiple study endpoints between V50 or V200 and P in this setting. Safety parameters observed in the V arms were generally similar to the P arm; no new safety signals of V were identified. Clinical trial information: NCT01657799
P N=102a | V50 N=103 | V200 N=102 | |
---|---|---|---|
Median age, years | 60 | 60 | 62 |
Sex, n Male | 56 | 61 | 66 |
Graded Prognostic Assessment (GPA), n ≤2.5 | 91 | 91 | 92 |
Median OS, d (95% CI) | 185 (137–251) | 209 (169–264) | 209 ( 138–255) |
Objective Response Rate, % | 41.2 | 36.9 | 42.2 |
Median time to clinical BM progression per event review board, d (95%CI) | 348 (216–NR) | 286 (192–NR) | 255 (204–342) |
Median time to radiographic BM progression per central imaging center, d (95%CI) | 259 (184–NR) | 226 (147–360) | 224 (137–358) |
All ADRs, % | 37 | 37 | 40 |
Gr 3/4 AEs, % | 43 | 28 (p=.040) | 26 (p=.012) |
a1 not dosed or included in the safety analysis; NR, not reached.
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