First-in-human trial of a poly(ADP-ribose) polymerase (PARP) inhibitor MK-4827 in advanced cancer patients (pts) with antitumor activity in BRCA-deficient and sporadic ovarian cancers.

Abstract

Sporadic platinum resistant high grade serous ovarian cancer* n=30 290 mg n=5 210 mg n=6 150 mg n=6 110 mg n=5 80 mg n=6 60 mg n=7 40 mg n=3 30 mg n=6 Key Inclusion and Exclusion Criteria Inclusion criteria • Parts A&B Age 18 or older Confirmed histological diagnosis Informed consent Adequate organ function ECOG PS of ≤ 2

Stumbling Blocks on the Path to Personalized Medicine in Breast Cancer: The Case of PARP Inhibitors for BRCA1/2-Associated Cancers

“…These agents have already begun to show potential as single therapies for tumors with known defects in HR repair in women with germline BRCA1 or BRCA2 mutations. As knowledge of tumor biology increases, it is possible that PARP inhibitors, used correctly, will figure into the treatment of sporadic cancers with specific a good safety profile, and clinical efficacy in both BRCAassociated and sporadic advanced solid tumors ( 14 ).…”

Clinical characteristics and outcomes of BRCA-associated ovarian cancer (OC): Genotype and survival.

“…Recent discoveries have prompted significant excitement regarding the role of PARP-inhibitors in the treatment of BRCA-associated EOC, with multiple studies demonstrating single-agent activity of these agents, even in patients with heavily-pre-treated disease (19,20,22,26,27). However, as patients have remained on these agents for prolonged periods of time, mechanisms of resistance have also emerged.…”

Biomarkers of PARP inhibitor sensitivity

“…Substantial efficacy has been shown with PARP inhibitors in the treatment of hereditary BRCA1/2 related Breast and Ovarian cancer as single agents [1][2][3] and in combination with temozolomide [4]. Similarly, encouraging activtity has been shown in sporadic ovarian cancer with a PARP inhibitor as a single agent [5], and in sporadic triple negative breast cancer in combination with gemcitabine/carboplatin chemotherapy [6].…”