Emily Menendez

GU Oncology Now

Poly(adenosine diphosphate&ndash;ribose) polymerase (PARP) inhibitors may offer a therapeutic benefit in patients with metastatic urothelial cancer (mUC). PARP inhibitors are the first approved targeted agent to manage DNA damage response (DDR) genes and have demonstrated a clinical benefit in patients with solid tumors who carry germline or somatic alterations in those genes.As somatic alterations in DDR genes are common in patients with advanced urothelial cancer, researchers <a href="https://ascopubs.org/doi/abs/10.1200/PO.23.00095" target="_blank" rel="noopener">examined the use of the PARP inhibitor olaparib</a> to determine the drug&rsquo;s potential therapeutic benefit in patients with mUC with somatic DDR alterations.The phase 2 study included 19 patients with mUC who harbored somatic DDR alterations. Nine patients (47.4%) had received prior cisplatin-based chemotherapy, 10 patients (52.6%) had alterations in homologous recombination (HR) genes, 8 patients (42.1%) had pathogenic BRCA2 mutations, and 2 patients had alterations in other HR genes. The median patient age was 66 years (range, 45-82 years).Patients were administered olaparib 300 mg twice daily, with a primary end point of objective response rate. Secondary end points were safety, progression-free survival (PFS), and overall survival (OS).The trial ended early before slow accrual; no patients achieved a partial response, but 6 patients achieved stable disease lasting 2.13 to 16.10 months. The median PFS was 1.9 months (range, 0.8-16.1 months), and the median OS was 9.5 months (range, 1.5-22.1 months).In patients with mUC and DDR alterations, olaparib demonstrated limited antitumor activity. This outcome may be due to poorly characterized functional implications of certain DDR alterations, or to cross-resistance with platinum-based chemotherapy.

DDR Mutations Not Linked to Clinical Benefit of Olaparib in mUC

Advanced Urothelial Carcinoma

PARP inhibitors may offer a therapeutic benefit in patients with urothelial cancer, offering a clinical benefit in patients who carry alterations in DDR genes.

About Us

Contributors and Partners

Editorial Policy

Advertising

eNewsletters

Calendar

Contact Us

Contribute

MashupMD

Cancer Nursing Today

Urban Health Today

Blood Cancers Today

DocWire News

Knowledge Hubs

Conference Coverage

Roundtables

The Uromigos

Uromigos Live 2024

AUC3

Localized

mHSPC/mCSPC

CRPC

Diagnostics

Prostate Cancer

Localized Renal Cell Carcinoma

Advanced Renal Cell Carcinoma

nccRCC

Renal Cell Carcinoma

Non-Muscle Invasive Urothelial Carcinoma

Muscle Invasive Urothelial Carcinoma

Upper Tract Urothelial Carcinoma

Urothelial Carcinoma

Testicular, Penile, and Rare Cancers

Video Insights

Advancements in Oncology

The Oncology Brothers

Expert Interviews

Journal

Subscribe