4.6 Article

A phase I study of talazoparib (BMN 673) combined with carboplatin and paclitaxel in patients with advanced solid tumors (NCI9782)

Journal

CANCER MEDICINE
Volume 11, Issue 21, Pages 3969-3981

Publisher

WILEY
DOI: 10.1002/cam4.4724

Keywords

BMN673; carboplatin; paclitaxel; PARP; talazoparib

Categories

Funding

  1. UW Comprehensive Cancer Center Support Grant (CCSG) [P30CA014520]
  2. John Hopkins Translational Science Team and Consortium for ETCTN Studies [UM1CA186691]

Ask authors/readers for more resources

This study aimed to determine the safety and tolerability of the PARP inhibitor talazoparib with carboplatin and paclitaxel in patients with advanced solid tumors. The results revealed that this combination therapy is associated with significant myelosuppression, and modifying the chemotherapy component may be necessary for further development.
Background Inhibitors of poly(ADP-ribose) polymerase (PARP) proteins potentiate antitumor activity of platinum chemotherapy. This study sought to determine the safety and tolerability of PARP inhibitor talazoparib with carboplatin and paclitaxel. Methods We conducted a phase I study of talazoparib with carboplatin AUC5-6 and paclitaxel 80 mg/m(2) days 1, 8, 15 of 21-day cycles in patients with advanced solid tumors. Patients enrolled using a 3 + 3 design in two cohorts with talazoparib for 7 (schedule A) or 3 days (schedule B). After induction with 4-6 cycles of triplet therapy, patients received one of three maintenance options: (a) continuation of triplet (b) carboplatin/talazoparib, or (c) talazoparib monotherapy. Results Forty-three patients were treated. The MTD for both schedules was talazoparib 250mcg daily. The main toxicity was myelosuppression including grade 3/4 hematologic treatment-related adverse events (TRAEs). Dose modification occurred in 87% and 100% of patients for schedules A and B, respectively. Discontinuation due to TRAEs was 13% in schedule A and 10% in B. Ten out of 22 evaluable patients in schedule A and 5/16 patients in schedule B had a complete or partial response. Twelve out of 43 patients received >= 6 cycles of talazoparib after induction, with a 13-month median duration of maintenance. Conclusion We have established the recommended phase II dose of Talazoparib at 250mcg on a 3- or 7-day schedule with carboplatin AUC6 and paclitaxel 80 mg/m(2) on days 1, 8, 15 of 21-day cycles. This regimen is associated with significant myelosuppression, and in addition to maximizing supportive care, modification of the chemotherapy component would be a consideration for further development of this combination with the schedules investigated in this study.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available