1650P - Identification of potential targets in pancreatic adenocarcinoma: The KRAS Wild-Type subset

Background

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited treatment benefits. However, about 10% of cases are KRAS wild-type (WT) which are enriched in potentially actionable molecular alterations (MA). We aim to shed light on the clinical and molecular features and explore the survival benefit from precision medicine in these patients (pts).

Methods

We conducted a comprehensive retrospective analysis of PDAC pts treated at Vall d’Hebron University Hospital from 2016 to 2022 and included those with KRAS WT and a molecular profile using next-generation sequencing (NGS). We classified MA using the ESMO Scale of Clinical Actionability for molecular Targets (ESCAT) and compared those in Tiers I-III treated with matched therapy to those who did not or without actionable MA. We used the Kaplan-Meier method and the log-rank test to compare overall survival (OS).

Results

We identified 45 KRAS WT pts with a median age of 57 years (range 29 - 75), 69% were male and 56% were metastatic at diagnosis. Among metastatic cases (n=36) median OS was 23.7 months (95% confidence interval (95CI) 18.4-43.4). Ten pts presented DNA damage repair (DDR) gene alterations (24%) and two presented deficient mismatch repair alterations (4.4%). Moreover, we identified pathogenic germline mutations in 8 pts and gene fusions in 8 pts (18%). The table outlines MA according to the ESCAT and matched therapy. Metastatic pts who received matched therapy (n=9) had longer OS compared to those who did not receive matched therapy (n=9) [(HR 0.49 (95CI 0.17-1.45) 34,3 vs 19 months p=0.2] or those without actionable MA (n=18) [(HR 0.86 (95CI 0.31-2,32) 21,8 months p=0.76].

Table: 1650P

Conclusions

Our findings suggest that KRAS WT PDAC tumours are enriched in potentially targetable MA and could benefit from precision-oncology approaches. These results highlight the relevance of performing a complete NGS analysis in these pts.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Vivancos: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Guardant Health, Bayer, Incyte; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol Myers Squibb, Roche, Incyte. R. Dienstmann: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, Ipsen, Libbs, Lilly, MSD, Roche, Sanofi, Servier, GSK, Takeda, Janssen, Foundation Medicine; Financial Interests, Personal, Advisory Board: Bayer, Roche; Financial Interests, Personal, Full or part-time Employment, Oncoclínicas is a private healthcare provider in Brazil. I work part time as Medical Director of the Precision Medicine and Big Data Initiative. We develop molecular tests (pathology and genomics) that are offered to patients treated in the organisation as part of support programs sponsored by pharmaceutical companies and I coordinate research activities with real-world clinic-genomics cohorts: Oncoclínicas; Financial Interests, Personal, Stocks/Shares: Trialing; Financial Interests, Personal, Research Grant: Merck. T. Macarulla: Financial Interests, Personal, Advisory Board: Ability Pharmaceutical, SL, AstraZeneca, Basilea Pharma, Batxer, BioLineRX Ltd, Celgene SLU, Eisai, IPSEN Pharma, Incyte; Financial Interests, Personal, Other, Direct research fund: Servier, Merck, Sharp and Dhome, Novocure, QED Therapeutics Inc., Roche, Sanofi-Aventis, Zymeworks; Financial Interests, Personal, Invited Speaker: Lilly, Janssen; Financial Interests, Institutional, Research Grant: Amc Medical Research, Armo Biosciences, Basilea, Biokeralty Research Institute, Merck Sharp & Dohme, Oncomed Pharmaceuticals, QED Therapeutics, VCN Biosciences, AbbVie Farmaceútica, Ability Pharmaceuticals, Agios, Amgen, Aslan, AstraZeneca, Bayer, BeiGene, Biolinerx, Blueprint Medicines, Boston Biomedical, Bristol Myers Squibb (BMS), Cantargia, Celgene, Eisai, Erytech Pharma, F. Hoffmann-la Roche, FibroGen, Genentech, Hallozyme, Immunomedics, Incyte, Ipsen, Lab. Menarini, Lilly, Loxo Oncology, MedImmune, Merimarck, Millenim, Nelum, Novartis, Novocure, Pfizer, Pharmacyclics, Roche, Zymeworks; Non-Financial Interests, Member: American Society of Clinical Oncology - ASCO, “Sociedad Española de Oncología Médica” – SEOM, Sociedad Europea de Oncología Médica - ESMO. All other authors have declared no conflicts of interest.