Introduction to Myelofibrosis and Highlights from the 2025 ASCO Annual Meeting

By: Lisa Astor
Posted: Friday, August 8, 2025

Rucaparib monotherapy demonstrated clinical benefit in a pantumor cohort of patients with solid tumors with pathogenic variants in homologous recombination repair genes, according to results of the phase II LODESTAR trial. Study findings, showing greater benefit among patients with a homologous recombination deficiency signature (HRDsig) positivity, were published in JCO Precision Oncology.

The study authors, including corresponding author Kim A. Reiss, MD, Associate Professor of Medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania, noted that their findings suggest that patients beyond those with canonical tumor histologies (ie, breast, ovarian, prostate, and pancreatic cancers) can benefit from treatment with PARP inhibitors.

LODESTAR is a single-arm study that enrolled 51 patients with solid tumors and pathogenic variants in BRCA1, BRCA2, PALB2, RAD51C, and RAD51D in cohort A. Twelve patients with variants in BARD1, BRIP1, FANCA, NBN, and RAD51B were enrolled in cohort B. The most common cancer types were breast cancer followed by non–small cell lung cancer (NSCLC), and the most common variants were BRCA2 followed by BRCA1. In order to identify potential biomarkers to predict sensitivity to rucaparib, the researchers conducted scar-based assays to identify HRD signatures and platinum sensitivity.

In cohort A, the overall response rate was 18% (95% confidence interval [CI] = 10%–30%). Across the entire study population, the disease control rate was 65% (95% CI = 53%–76%), the median progression-free survival was 5.5 months (95% CI = 3.68–7.82), and the median OS was 12.1 months (95% CI = 10.6 to inferred).

The overall response rate was significantly higher among tumors with HRDsig positivity compared with HRDsig-negative tumors (32% vs 0%; P < .01). Tumors with pathogenic variants from genes in cohort A were more likely to be HRDsig positive than those with variants from genes in cohort B. For tumors with platinum sensitivity, the median progression-free survival was 7.8 months vs 3.5 months (hazard ratio [HR] = 0.11; 95% CI = 0.02–0.55; P = .02).

Disclosure: For full disclosures of the study authors, visit ascopubs.org.

JCO Precision Oncology

---