American Association for Cancer Research, April 5-10

The annual meeting of the American Association for Cancer Research was held this year from April 5 to 10 in San Diego, drawing approximately 19,000 participants from around the world, including scientists, cancer survivors, clinicians, allied health professionals, and industry professionals. The conference highlighted recent advances in the treatment, management, and prevention of cancer.

As part of the phase I/II PETRA multicenter clinical trial, Timothy A. Yap, M.B.B.S., Ph.D., of the University of Texas MD Anderson Cancer Center in Houston, and colleagues found that saruparib, a selective inhibitor of poly-ADP ribose polymerase 1 (PARP1), is associated with favorable efficacy and safety among patients with certain homologous recombination repair (HRR)-deficient breast cancers.

The investigators evaluated the safety and efficacy of saruparib among 306 patients with previously treated HRR-deficient breast, ovarian, pancreatic, or prostate cancer. They found that saruparib demonstrated a favorable safety and tolerability profile, with no unexpected safety findings. Adverse events leading to dose reduction or treatment discontinuation were infrequent and generally mild. Saruparib pharmacokinetics appeared to be linear and demonstrated robust target engagement. At the 60-mg once-daily dose, saruparib delivered promising efficacy, with deep and durable responses (overall response rate, duration of response, and median progression-free survival) observed in a heavily pretreated population of patients with breast cancer harboring HRR mutations (e.g., BRCA1, BRCA2, PALB2, RAD51C, and RAD51D). In collaboration with the U.S. Food and Drug Administration as part of Project Optimus, saruparib 60 mg once daily was established as the optimal recommended monotherapy dose to maximize efficacy and tolerability.

“Saruparib is a first-in-class, potent new-generation PARP inhibitor with high selectivity for PARP1. Saruparib has a wide therapeutic index, superior pharmacokinetic/pharmacodynamic properties, and efficacy compared with approved PARP inhibitors, and is conveniently administered as a once-daily dose,” Yap said. “The favorable safety profile of saruparib together with the low rate of dose reduction compared with approved PARP inhibitors may allow patients to remain on treatment longer at an optimal dose with superior drug exposures and maximal target engagement, which could lead to improved efficacy.”

The study was funded by AstraZeneca, the manufacturer of saruparib.

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In another study, Edward Cliff, M.B.B.S., M.P.H., of Brigham and Women”s Hospital and Harvard Medical School in Boston, and colleagues found that more than five years after a cancer drug goes through accelerated approval, more than half of drug-indication pairs have yet to demonstrate clinical benefit.