Health outcomes of gBRCA testing strategies for metastatic pancreatic cancer patients.

Abstract

537 Background: About 4-8% metastatic pancreatic cancer (mPC) patients have germline BRCA mutation (gBRCAm). Identifying gBRCAm through early testing benefits mPC patients through: 1. better health outcomes when gBRCAm patients receive platinum (plat) based 1st line (1L) chemotherapy compared to non-plat 1L regimen; 2. additional benefit, if eligible, from olaparib (O) maintenance treatment (mTx), which was approved by the FDA for the gBRCAm mPC patients who have not progressed on at least 16 weeks of a 1L plat regimen. Objective: To evaluate the health outcomes of gBRCA testing and treatment strategies among mPC patients using simulation model. Methods: A 3-state partitioned survival model was developed to assess the lifetime (20 year) health outcomes among treatment naïve mPC patients for the following strategies: 1. No gBRCA testing, no O mTx; 2. gBRCA testing before 1L, no O mTx; 3. gBRCA testing before 1L, O mTx; 4. gBRCA testing after 1L, O mTx. Without gBRCAm information before 1L (i.e., strategy 1&4) or if gBRCA negative, 45% mPC patients with good performance status (PS) and 27% with poor PS received 1L plat. We assumed that for gBRCAm patients, if known, 90% with good PS and 50% with poor PS received 1st line plat (i.e., strategy 2&3) in the base case. We assumed gBRCA testing had 100% of sensitivity and specificity. OS and PFS survival curves were extrapolated from pivotal trials. The additional health outcome benefit from O mTx after 16 weeks were modeled using efficacy from POLO trial. Health outcomes were measured by life years (LY) and, after applying health utilities by health state, quality adjusted life years (QALY). Results: The proportion of gBRCAm mPC patients receiving O mTx were 58.7% (4.4% of mPC patients) for strategy 3 vs 30.0% (2.2% of mPC patients) for strategy 4. For gBRCAm mPC patients, no testing generated the least LY and QALY, while testing before 1st line with O mTx resulted in the most. This trend was also observed in the overall cohort of mPC patients with the best outcomes from testing before 1st line with O mTx and worse outcomes from no testing or testing after 1st line with O Mtx. These survival gains are primarily derived by higher proportion of patients on platinum with better survival along with O Mtx gains. Conclusions: mPC patients achieve the highest health benefits by gBRCA testing before 1L treatment followed by O mTx, even with less than 5% mPC patients becoming eligible for O mTx (strategy 3).[Table: see text]