Abstract 1479P
Background
Pancreatic Ductal Adenocarcinoma (PDAC) harboring germlineBRCA1-2 pathogenic variants (gBRCA1-2pv) is emerging as a distinct entity, benefitting from specific treatments (platinum agents, PARP-inhibitors). Information on second-line therapy (2LT) outcome in this setting is lacking.
Methods
Clinical data of stage IV PDAC patients (pts) carrying gBRCA1-2pv receiving a 2LT were retrospectively collected from 23 Italian Centers and descriptively analyzed, focusing on RECIST response and survival outcome. Progression-free and Overall survival2 (PFS2 and OS2) were calculated from 2LT start to 2nd progression or death, respectively.
Results
49 out of 63 pts treated with first-line therapy (1LT) between December 2008 and July 2020 had Progressive Disease (PD) at time of database lock: 7 pts (4 treated without platinum) did not receive subsequent therapies, while 42 (86%) started a 2LT, whose outcome was assessable in 40 pts (2 had immature follow-up). ECOG Performance Status at diagnosis was ≤1 in 38 (95%) pts, 32 (80%) had liver metastases, median age was 62 (39-84) years. RECIST responses of the 19 and 18 pts receiving platinum- and non-platinum-based multidrug 2L were 47% vs 28% partial responses, 21% vs 33% stable diseases and 32% vs 39% PD, respectively. Median PFS for 1LT (mPFS1), mPFS 2, mOS2 and total median OS (mOStot) are shown in the Table. Table: 1479P
Clinical characteristics and survival outcomes
| Variable | N | mPFS2 (mo) | mOS2 (mo) | mPFS1 (mo) | mOStot (mo) |
| All patients | 40 | 5.3 | 9.8 | 7.5 | 19.9 |
| Germline BRCA pathogenic variant 1 2 | 8 32 | 3.0 6.6 | 6.0 11.3 | 5.3 7.9 | 12.7 20.9 |
| Gender male female | 17 23 | 6.2 4.3 | 10.4 8.4 | 8.5 6.2 | 17.4 20.1 |
| Age (years) ≤ 65 > 65 | 29 11 | 6.5 3.1 | 12.5 6.8 | 8.5 5.9 | 21.1 12.8 |
| I line chemotherapy Nab-paclitaxel + Gemcitabine (m)FOLFIRINOX/PAXG/PEXG GEMOX/FOLFOX Gemcitabine | 18 14 6 2 | 8.1 5.3 2.6 2.4 | 11.8 11.4 2.8 3.6 | 6.0 11.6 5.3 3.9 | 19.9 26.8 10.8 8.1 |
| II line chemotherapy Platinum NO Platinum Gemcitabine or Capecitabine | 19 18 3 | 8.7 5.3 2.4 | 12.0 7.4 4.9 | 5.9 9.5 3.5 | 21.1 18.7 9.7 |
| Previous PFS1 (mo) ≤ 6 > 6 | 16 24 | 6.8 5.3 | 10.6 8.8 | - - | 14.7 21.5 |
mo: months
Conclusions
Keeping in mind the small sample size of our series, gBRCA1pv and > 65 years pts yielded limited benefit from 2LT. Platinum-based 2LT obtained longer PFS2 and OS2 as opposed to platinum-free 2LT. Pts with PFS1 ≤ 6 months had longer PFS2 and OS2, but shorter OStot if compared to pts with PFS1 > 6 months. Overall, 2L data confirm that platinum is the backbone of treatment for gBRCA1-2pv stage IV PDAC pts, but first-line use should be preferred.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
MyEverest ONLUS.
Disclosure
M. Milella: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: EUSA Pharma; Financial Interests, Personal, Invited Speaker: Merck-Serono; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Mylan. M. Niger: Financial Interests, Personal, Invited Speaker: Accademia della Medicina; Financial Interests, Personal, Other, Consultant: EMD Serono; Financial Interests, Personal, Other, Consultant: Basilea Pharmaceutica. S. Cascinu: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Baxter; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Other, Consultant: Amgen; Financial Interests, Personal, Other, Consultant: Baxter; Financial Interests, Personal, Other, Consultant: Eli Lilly; Financial Interests, Personal, Other, Consultant: Celgene; Financial Interests, Personal, Other, Consultant: Novartis; Financial Interests, Personal, Other, Consultant: MSD; Financial Interests, Personal, Research Grant: Celgene; Financial Interests, Personal, Research Grant: Eisai. M. Reni: Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Baxalta; Financial Interests, Personal, Advisory Board: Baxter; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Shire; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novocure; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, steering committee: AstraZeneca; Non-Financial Interests, Personal, Other, steering committee: Boston Pharmaceuticals. All other authors have declared no conflicts of interest.