Veliparib with gemcitabine, radiotherapy safe for locally advanced pancreatic cancer
Veliparib, a poly (ADP-ribose) polymerase (PARP)-1/2 inhibitor, with gemcitabine and radiotherapy (RT) is safe and effective for patients with locally advanced pancreatic cancer (LAPC), a recent study has found.
The open-label single-arm phase 1 clinical trial included 30 LAPC patients (median age 68 years; 40 percent male), who were given weekly gemcitabine with daily intensity modulated RT (IMRT). Veliparib was also administered at 20 mg twice-daily for 3 weeks, with dose escalation using a Bayesian adaptive design.
The maximum tolerated dose of veliparib was 40 mg twice-daily with 400 mg/m2 gemcitabine and 36 Gy/15 fractions of RT. Treatment was reasonably safe, with 16 dose-limiting toxicities observed in 12 patients. Gastrointestinal, haematologic and fatigue problems were the most common adverse events. No grade 5 toxicities were reported.
The median progression-free survival (PFS) and overall survival (OS) were 9.8 and 14.6 months, respectively. By data cut-off, majority (83 percent; n=25) of the participants had had their disease progress and 80 percent (n=24) had died.
Stratified according to the DNA damage repair pathway, median PFS was higher in those with altered than in patients with an intact pathway (19 vs 14 months).
Multivariate Cox proportional hazards analysis showed that enhanced expression of the PARP3 (hazard ratio [HR], 0.49; 95 percent CI, 0.21–0.99; p=0.048) and attenuated expression of the Ring-Box 1 (HR, 3.01; 1.12–8.59; p=0.03) genes were associated with better OS. However, researchers emphasize that these are exploratory analyses and should be validated in larger trials.