Abstract 1549P
Background
Treatment of pancreatic cancer is still a challenge, despite advances in precision medicine there is a lack of predictive biomarkers beyond BRCA 1/2 germline mutations. KRAS WT PC patients (pts) constitutes a small subgroup, accounting 7% of all PC tumors. Different clinical characteristics have been described in these pts but a complete understanding of molecular drivers is lacking. We aim to describe MA with therapeutic implications in a KRAS WT prospective cohort participating in prescreening program.
Methods
We identified PC pts with KRAS WT tumors in whom comprehensive in-house NGS analysis (tumor and normal) was performed between June 2016 and December 2019. Clinical data were obtained from medical records and MA (mutations [mut] and fusions) from structured databases.
Results
Twenty-nine patients were analyzed (median age 58 years, 69% female), 15 (51%) patients had locally advanced or metastatic disease at diagnosis. Liver metastases were present in 15 (58%) of 26 pts with advanced disease and first line treatment was FOLFIRINOX and gemcitabine plus nab-paclitaxel in 10 (38%) and 12 (46%) pts respectively. With a mean follow-up time of 21.6 months since the diagnosis of advanced disease, the overall survival was 14.1 months. Fourteen different potentially actionable somatic alterations were found in 17 (58%) pts including DNA damage repair alterations [BRCA2 mut (4), BRCA1 mut (2), ATM mut (2), PALB2 (1)], kinase fusions [BRAF (1), RET (1), NRG1 (1)], and others [BRAF V600E mut (1), ERBB3 mut (1), PIK3CA mut (1), STK11 mut (1), RNF43 mut (2), NOTCH1 mut (1), CDKN2A del (1)]. From DNA damage repair alterations, most were germline events in 6 pts (20%), which included BRCA2 mut (3), BRCA1 mut (1), ATM mut (1) and PALB2 mut (1).
Conclusions
In this cohort of patients with KRAS WT advanced PC, we confirmed enrichment for potentially targetable MA, both somatic and germline, and this represents a great opportunity for targeted treatments in clinical trials. We believe that determination of KRAS status is imperative in all PC patients and a broad molecular profiling should be prioritized in the KRAS WT population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H. Verdaguer: Advisory/Consultancy: Ipsen. J. Hernando: Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Resultados de la búsqueda Resultado web con enlaces al sitio web Advanced Accelerator Applications; Speaker Bureau/Expert testimony: Angelini. I. Baraibar Argota: Honoraria (self): Sanofi; Travel/Accommodation/Expenses: Amgen. R. Dienstmann: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Servier; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Research grant/Funding (institution): Merck ; Research grant/Funding (institution): Pierre Fabre. T. Macarulla Mercadé: Advisory/Consultancy: Advance Medical HCMS; Advisory/Consultancy: Batxer; Advisory/Consultancy: BioLineRX Ltd; Honoraria (institution), Advisory/Consultancy: Celgene SLU; Advisory/Consultancy: Eisai; Advisory/Consultancy: Genzyme; Advisory/Consultancy: Incyte; Advisory/Consultancy: IPSEN; Advisory/Consultancy: Lab. Menarini; Advisory/Consultancy: Servier; Honoraria (institution), Advisory/Consultancy: Lilly; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: Merck Sharp and Dhome; Advisory/Consultancy: Prime Oncology EU; Advisory/Consultancy: QED Therapeutics Inc; Advisory/Consultancy: Sanofi-Aventis; Honoraria (institution): Agios; Honoraria (institution): Aslan; Honoraria (institution): AstraZecena; Honoraria (institution): Bayer; Honoraria (institution): Genentech; Honoraria (institution): Hallozyme; Honoraria (institution): Immunomedics; Honoraria (institution): Merimarck; Honoraria (institution): Millenim; Honoraria (institution): Novartis; Honoraria (institution): Pfizer; Honoraria (institution): Pharmacyclics; Honoraria (institution): Roche. All other authors have declared no conflicts of interest.