1634P - Extensive molecular profiling of KRAS wild-type versus KRAS mutant pancreatic ductal adenocarcinoma on 233 patients

Background

Molecular profiling is increasingly implemented to guide treatment of pancreatic ductal adenocarcinoma (PDAC), especially if enrolment in clinical trials is considered. The aim of our study was to describe actionable alterations detected in KRAS mutant (KRASm) versus KRAS wild-type (KRASwt) PDAC, as the latter is considered as harboring more molecular alterations.

Methods

This monocentric prospective study included patients with locally advanced or metastatic PDAC who underwent next-generation sequencing (NGS) on liquid biopsy and/or tissue sample between 2015 and 2022 (FoundationOne® CDx, Liquid CDx or Oncomine Comprehensive Assay), as part of the BIP study (NCT02534649).

Results

233 patients with a PDAC underwent NGS: 63 on tissue samples alone, 95 on liquid biopsies alone, and 75 on both tissue and liquid. Among 170 liquid biopsies, 90 were informative (52.9%). Among 196 patients with informative NGS, 172 patients (87.8%) had a KRASm PDAC, and 24 a KRASwt PDAC (12.2%). Median overall survival (OS) in the KRASwt group was 27.8 versus 20.3 months for KRASm patients (HR 0.58, CI (0.39-0.87), p=0.02). ESCAT alterations were found in 17.3% of total population, 25.0% in KRASwt group and 16.3% in KRASm group. All 7 BRCA1/2 germline mutations were detected in the KRASm group. 1 NTRK fusion was found in a KRASwt PDAC. BRCA1/2 somatic mutations, PIK3CA hotspot mutations, MDM2 amplifications and ERRB2 alterations were found similarly in both groups. We detected 5 KRAS G12C mutations. Patients harboring ESCAT alterations had a median OS of 25.0 versus 19.6 months for those without (HR 0.85, 95%CI (0.58 – 1.23), p=0.40). 66 patients (33.7%) were eligible to early-phase trials according to the molecular tumor board and 10 patients (5.1%) were effectively enrolled, with a range of time to progression between 22 days and 11 months.

Conclusions

Although actionable mutations are more prevalent in the KRASwt group, 16.3% of KRASm patients harbored ESCAT alterations, underlying the need for molecular profiling regardless of KRAS status.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. L. Blouin: Financial Interests, Personal, Other: AstraZeneca. S. Cousin: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Pfizer, BMS, Novartis, AbbVie; Financial Interests, Personal, Principal Investigator: MSD, BMS, Sanofi, AbbVie, Roche. S. Pernot: Financial Interests, Personal, Invited Speaker: Bayer, Amgen, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Servier, Merck. All other authors have declared no conflicts of interest.