Curiouser and curiouser.

TBCRC 024 was a pretty standard phase 1 trial. Until it wasn't. It was designed to determine the max tolerated dose (MTD) of veliparib concurrent with postmastectomy radiation (PMRT) in patients with inflammatory or recurrent breast cancer. The rationale was preclinical data indicating PARP inhibitors may radiosensitize breast cancer cells--that and doing anything with PARP inhibitors was totally in vogue a few years back. Since then we’ve learned that, without the pre, clinical utility of veliparib is questionable at best. Back to the study. 5 of 30 patients (17%) experienced dose limiting toxicities at veliparib doses of 100-200 mg BID, well below the pre-defined MTD threshold of 30% at 4 weeks. Story’s not over. There happened to be a hefty rate of late chest wall fibrosis, occurring in 6 of 15 patients alive at 3 years. In a strange turn of events, the authors concluded that the lowest tested veliparib dose of 50 mg BID should move on to the phase 2 component. TBL: Veliparib concurrent with PMRT may result in significant late chest wall fibrosis, and phase 1 trials are confusing. | Jagsi, J Clin Oncol 2018