PLATINUM THERAPY FOR ADVANCED PROSTATE CANCER

NEW YORK (Reuters Health) - Platinum-based treatment is associated with antitumor activity in patients with advanced prostate cancer with DNA-repair-gene aberrations, according to a multinational group of researchers.

Genomic aberrations that impair DNA-repair genes occur at a frequency of up to 30% in advanced prostate cancer, Dr. Sabine Schmid of Princess Margaret Cancer Centre, in Toronto, Canada, and colleagues note in JAMA Network Open. Some have been associated with sensitivity to platinum compounds and/or PARP inhibitors.

To find out if platinum-based therapy might be beneficial in patients with castration-resistant prostate cancer (CRPC), as it is known to be in certain patients with triple-negative breast cancer, the team examined data on 508 patients from 25 academic centers in 12 countries. The men's median age was 61 years.

For most patients (65%), there were no data on DNA-repair-gene aberrations, but such aberrations were found to be present in 80 patients (14.7%) and absent in 19.3%. The most common aberration consisted of alterations in BRCA2 seen in 44 patients.

Eighty percent of patients received a platinum-combination treatment with drugs including docetaxel, etoposide and paclitaxel. Only 100 patients were given platinum-based monotherapy with carboplatin.

A prostate-specific antigen (PSA) decrease of at least 50% was seen in 47.1% of patients with DNA-repair aberrations and 36.1% of those with negative testing. Corresponding proportions for soft-tissue responses in evaluable patients were 48.3% and 31.3%.

In the subgroup of patients with BRCA2 gene alterations, PSA level decreases of at least 50% were seen in 23 patients (63.9%). Soft tissue responses were seen in 17 of the 34 patients (50.0%) with evaluable disease.

In the 284 patients without DNA profiling, 28.5% showed a PSA decrease of at least 50%, and soft-tissue response was reported in 38 of 185 (20.5%) with evaluable disease.

"Based on our analysis," the researchers conclude, "platinum-containing therapy should be considered in patients with DNA repair gene aberrations especially if access to a PARP inhibitor is not available."

In an accompanying editorial, Drs. Frederick J. Meyers and Mili Arora of the University of California, Davis, in Sacramento, note that comprehensive sequencing of human cancers is "revealing that seemingly disparate malignant neoplasms may be more similar than not."

Dr. Meyers told Reuters Health by email, "The similarity in genomic alterations and responsiveness to targeted therapy between triple-negative breast cancer (TNBC) and hormone refractory prostate cancer has not been previously emphasized. Prospective trials that include deeper sequencing and detailed phenotyping of both groups of patients is likely to refine this observation."

Dr. Schmid did not respond to requests for comments.