Niraparib has antitumor activity and manageable toxicity in men with pretreated metastatic castration-resistant prostate cancer and DNA repair gene defects, shows a phase 2 trial.

Platinum-based chemotherapy is active in patients with advanced castration-resistant prostate cancer and DNA repair gene alterations, shows a chart review.

Germline pathogenic variants, primarily in DNA damage repair genes, are present in about 12% of patients with malignant pleural mesothelioma, report US researchers.

In patients with metastatic urothelial carcinoma treated with agents targeting programmed cell death protein 1 or its ligand, the presence of alterations in tumoral DNA damage response and repair genes is associated with better outcomes, findings indicate.

Normalized expression levels of the DNA repair protein MRE11 could help to identify patients with nonmetastatic muscle-invasive bladder cancer likely to benefit from bladder-preserving trimodality therapy, suggests research.

Finally, they comment on results indicating that DNA repair alterations can predict response to chemotherapy, as well as the general need for biomarkers to guide patient selection and treatment decisions.

There were no significant associations between NLR and selected variants of interest, namely EGFR , KRAS , TP53 , KEAP1 , STK11 , SMARCA4 , ARID1A , and targeted DNA damage response and repair genes.

The cabozantinib comparison of the double-blind, phase 2 ATLANTIS trial included 61 patients (instead of the planned 140) with stage IV urothelial cancer who derived clinical benefit (response or stable disease) from four to eight cycles of first-line chemotherapy, and did not harbor DNA repair deficiency or androgen receptor biomarkers.

Results from the ATLANTIS trial platform indicate that rucaparib could play a role in the maintenance treatment of metastatic urothelial carcinoma with a DNA repair deficiency that has responded to first-line platinum-based chemotherapy.

Furthermore, the radiographic PFS benefit of add-on olaparib was observed both in patients with and without HRR gene mutations (n=226 and 552, respectively), as detected by circulating tumor DNA testing, with significant hazard ratios (HRs) in favor of olaparib of 0.50 and 0.76, respectively.

Phase 2 study data show that the PARP inhibitor talazoparib has antitumor activity in men with heavily pretreated metastatic castration-resistant prostate cancer bearing DNA damage response alterations in genes associated with homologous recombination repair.

Masayuki Hagiwara (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and co-investigators investigated PARP1 as a potential biomarker because “[s]everal recent studies have shown that the absence of PARP alters the tumor immune microenvironment by inhibiting repair of DNA damage, thereby promoting response to ICI [therapy].”

Sumanta Pal (City of Hope Comprehensive Cancer Center, Duarte, California, USA) reported the results for the phase 2 trial of the first-in-class ataxia telangiectasia and Rad3-related (ATR) inhibitor, which is thought to have synergy with the chemotherapy agents via the disruption of DNA repair.

These individuals had at least one of either DNA mismatch repair deficiency (MMRD), DNA damage repair deficiency excluding MMRD, or a high level (>20%) of tumor infiltrating lymphocytes (TILs).

A prognostic model based on eight DNA repair-related genes may help identify women with breast cancer who are at high risk for death, Chinese researchers report.

Although platinum agents are considered to be “particularly active in cancer cells with DNA repair deficiency,” the researchers did not find a significant difference in the DFS benefit afforded by the paclitaxel–carboplatin combination between women with versus without germline BRCA1 / 2 mutations.

Clinically significant pathogenic/likely pathogenic germline variants, particularly in DNA damage repair genes, are common in patients with advanced urothelial cancer according to sequencing data.

The degree of response to olaparib among patients with heavily pretreated metastatic castration-resistant prostate cancer varies according to the type of DNA damage repair alteration the tumor carries, research shows.