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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Friday, April 19, 2024
In the phase I/Ia PETRA study, investigators found that the new-generation PARP inhibitor saruparib showed activity in various solid tumors, including HER2-negative breast cancer. These findings, which were presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract CT014), suggest potential improvements in clinical efficacy and safety compared with approved PARP inhibitors.
“Saruparib at 60 mg [once daily] demonstrated deep and durable responses with a high response rate and tumor reduction in the majority of patients,” stated Timothy A. Yap, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston, in a press release.
The study included patients with advanced HER2-negative breast, ovarian, prostate, or pancreatic cancer with BRCA1/2, PALB2, or RAD51C/D mutations and fewer than one prior PARP inhibitor. Phase IA evaluated dose escalation of saruparib (10–140 mg), and phase IB evaluated dose expansions at 20, 60, and 90 mg in PARP inhibitor–naive patients. The primary endpoint was safety. Secondary endpoints were pharmacokinetics, pharmacodynamics, preliminary efficacy, and circulating tumor DNA (ctDNA) analysis.
As of June 2023, 203 patients received saruparib: 113 in phase A and 90 in phase B. Overall, 60 mg was well tolerated, with low rate of dose reductions or discontinuation. Saruparib showed higherfold pharmacokinetics coverage over the target effective concentration at all doses compared with approved PARP inhibitors and durable PARylation inhibition greater than 90% in tumor biopsies and peripheral blood mononuclear cells at all doses. The objective response rate in patients with breast cancer trended higher at 60 mg and 90 mg than at 20 mg.
In phase II, overall response rate in 31 patients treated with 60 mg was 48.4%, and the median progression-free survival was 9.1 months. A total of 16 of 21 patients (76%) evaluable for ctDNA had a molecular response prior to the first scan. According to the study authors, this finding may support ctDNA kinetics as an early predictive biomarker for efficacy.
Disclosure: For full disclosures of the study authors, visit abstractsonline.com.
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