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Platinum Therapy May Up Survival in Pancreatic Cancer With DNA Repair Defects

TUESDAY, May 26, 2020 -- For patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC), those with homologous recombination deficiency (HRD) have improved survival with first-line (1L) platinum treatment, according to a study published online May 22 in Clinical Cancer Research.

Wungki Park, M.D., from Memorial Sloan Kettering Cancer Center in New York City, and colleagues examined progression-free survival (PFS) and overall survival (OS) in advanced-stage PDAC. Homologous recombination gene mutations (HRm) were assessed in various genes and HRm status was grouped as germline versus somatic; core (BRCAs and PALB2) versus noncore; and monoallelic versus biallelic.

The researchers found that 50 of 262 patients (19 percent) had HRD (15 percent germline and 4 percent somatic). Due to lack of difference in genomic instability and outcomes, the groups were analyzed together. Patients were followed for a median of 21.9 months. The median OS was 15.5 months and median PFS was seven months. Improved PFS was seen for patients with HRD versus no HRD when treated with 1L platinum (hazard ratio, 0.44), but not with 1L-nonplatinum. HRD patients had improved OS regardless of their firstline treatment in a multivariable analysis; however, most had platinum exposure during their course. Higher genomic instability was seen with biallelic HRm and core HRm (11 and 12 percent, respectively), which translated to improved PFS on 1L-platinum versus 1L-nonplatinum.

"HR deficiency defined by pathogenic mutation of core HR genes and loss of both copies of either core or noncore HR genes confers the greatest platinum sensitivity," Park said in a statement.

Several authors disclosed financial ties to the biopharmaceutical industry.

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