O'Reilly 2020: gemcitabine and cisplatin with or without veliparib in pancreatic cancer with a germline BRCA or PALB2 mutation
In the first randomised trial restricted to pancreatic cancer patients with inherited BRCA or PALB2 mutations, platinum chemotherapy shrank tumours in about two-thirds and gave unusually long survival, while adding the PARP inhibitor veliparib to the chemotherapy did not help and added toxicity.
Overview
Randomised multicentre phase 2 trial in 50 patients with untreated locally advanced or metastatic pancreatic adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation, assigned to gemcitabine plus cisplatin with or without veliparib.
Objective response rates were about 74 percent with veliparib and 65 percent without, not significantly different, and median overall survival was 15.5 against 16.4 months. Haematological toxicity was greater with veliparib. Across both arms, two-year survival was about 31 percent and three-year survival about 18 percent, far above unselected pancreatic cancer.
- Objective response about 74 percent with veliparib versus 65 percent with gemcitabine and cisplatin alone; median overall survival 15.5 versus 16.4 months.
- Two-year survival about 31 percent and three-year about 18 percent across both arms.
- More haematological toxicity with veliparib.
Gemcitabine plus cisplatin is a validated platinum doublet for BRCA or PALB2 carriers, and the trial explains why PARP inhibitors are used as maintenance after platinum rather than concurrently with it.
- A 50-patient phase 2 without a non-platinum comparator, so the platinum benefit is inferred from historical controls.
- PALB2 carriers were few.
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