Abstract 367P
Background
One-third of patients with pancreatic ductal adenocarcinoma cancer (PDAC) respond to first-line platinum-based therapy (PT) with a median duration of response of 5.9 months. However, 5-9% of patients carrying a pathogenic variant in genes involved in homologous recombination (BRCA1, BRCA2, PALB2) have shown increased chemosensitivity to platinum agents and a better prognosis. The number of PALB2 mutation (mPALB2) carriers analyzed to date is limited to date and best treatment requires further investigation. We aimed to describe the clinical characteristics and chemotherapy (cht) response of a multicenter cohort of mPALB2 PDCA patients (pts).
Methods
Observational study done at 6 hospitals in Spain. Eligible pts had to have a deleterious mPALB2, histologically confirmed PDAC and had to have received at least one line of cht. The primary endpoint was overall response rate (ORR) to first and subsequent lines of cht determined by RECIST v1.1. Measured additional outcomes were median duration of response (mDOR), disease control rate (DCR), time to first progression (TTP) and time to second progression (TTP2).
Results
A total of 18 mPALB2 PDCA pts were included. Median age at diagnosis was 58. Two pts had early disease (ED), 5 locally advanced (LAD) and 11 advanced disease (AD). Among 16 pts (LAD and AD), the ORR was 62.5%: 60% in pts treated with PT and 66.6% in non-platinum-based therapy (NPT). The mDOR was 9.6 months: 11.6 in PT group and 7.7 in NPT group (p=0.67). The DCR was 62.5% (63.6% in PT pts and 60% in NPT pts). mTTP1 was similar in PT and NPT group (10.2 and 11.2 months). For second line: ORR was 66.6% and mDOR was 3.5 months No differences were found between PT and NPT pts (60% ORR in PT vs 50% in NPT and 5 months in PT vs 3.1 months in NPT, p= 0.99). The DCR in second-line therapy was 88.8% (60% in PT and 100% in NPT pts), and the median TTP2 was 6.9 months (7.17 in PT and 6.5 in NPT).
Conclusions
The chemosensitivity observed in pts with mPALB2 PDCA in first and second line is clinically significant compared to what would be expected in pts with tumors proficient in homologous recombination repair and regardless of the use of platinum agents. This study support the importance of testing PDCA pts who are candidates for cht.
Legal entity responsible for the study
Hospital de la Santa Creu i Sant Pau.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.