Question: My father has pancreatic cancer and his doctors mentioned PARP inhibitors. What are these and when are they used?

Grading rubric:
description: The response should describe PARP inhibitors as a class of targeted agents that block the PARP enzyme, which is involved in repairing single-strand DNA breaks.
description: The response should mention that PARP inhibitors can be used in advanced pancreatic cancer when there is a germline mutation in a BRCA gene.
description: The response should mention that PARP inhibitors are used as maintenance therapy in patients with metastatic pancreatic cancer who have a germline BRCA1 or BRCA2 mutation and whose cancer has not progressed after at least 16 weeks of first-line platinum-based chemotherapy.
description: The response should mention that comprehensive germline testing for BRCA mutations is recommended for all patients with pancreatic cancer to identify those eligible for this targeted approach.
description: The response should mention that the American Society of Clinical Oncology specifically recommends olaparib, based on the POLO trial, which demonstrated a significant improvement in progression-free survival compared to placebo, without compromising quality of life.
description: The response should mention that other PARP inhibitors and combination strategies are under investigation, but their use remains investigational at this time. Based on the NCCN Guidelines Version 2.2025: Principles of Systemic Therapy for Pancreatic Adenocarcinoma (Metastatic Disease, First-Line Therapy) across performance status groups. For Good PS (0–1), preferred regimens include FOLFIRINOX (category 1 or modified FOLFIRINOX), Gemcitabine + albumin-bound paclitaxel (category 1), and NALIRIFOX (category 1). For patients with BRCA1/2 or PALB2 mutations, preferred options are FOLFIRINOX (category 1 or modified FOLFIRINOX) and Gemcitabine + cisplatin (category 1). Other recommended regimens include Gemcitabine (category 1), Gemcitabine + erlotinib (category 1), Gemcitabine + capecitabine, Gemcitabine + albumin-bound paclitaxel + cisplatin, Fluoropyrimidine + oxaliplatin, CapeOx (category 2B), OFF (category 2B), and GTX (category 2B). For Intermediate PS (2), preferred regimens include Gemcitabine + albumin-bound paclitaxel (category 1), Capecitabine, Gemcitabine, 5-FU + leucovorin + oxaliplatin (FOLFOX), 5-FU + leucovorin + irinotecan (FOLFIRI), and CapeOx. For Poor PS (3), Palliative and best supportive care is recommended, though options include Capecitabine (category 2B), continuous infusion 5-FU (category 2B), and Gemcitabine (standard or fixed-dose-rate infusion). Across all PS groups, therapies useful in certain circumstances include targeted agents: Entrectinib, Larotrectinib, and Repotrectinib (for NTRK gene fusion–positive tumors); Pembrolizumab (for MSI-H, dMMR, or TMB-H ≥10 mut/Mb); Selpercatinib (for RET gene fusion–positive tumors); and Dabrafenib + trametinib (for BRAF V600E mutation–positive cases). The guidelines note that all regimens are category 2A unless otherwise indicated, and patients with poor PS derive marginal benefit from systemic therapy.
description: The response should recommend that the user discuss this case with an oncologist.