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. 2023 Nov:194:113338.
doi: 10.1016/j.ejca.2023.113338. Epub 2023 Sep 9.

Clinical and genomic characterisation of early-onset pancreatic cancer

Florian Castet  1 , Carles Fabregat-Franco  1 , Gloria Castillo  2 , Víctor Navarro  2 , Alexandre Sierra  3 , Daniel Alejandro Acosta  3 , Daniel López-Valbuena  1 , Rodrigo Dienstmann  2 , Josep Tabernero  4 , Ana Vivancos  5 , Tian V Tian  6 , Teresa Macarulla  7
Affiliations

Clinical and genomic characterisation of early-onset pancreatic cancer

Florian Castet et al. Eur J Cancer. 2023 Nov.

Abstract

Background: The incidence of early-onset pancreatic cancer (EOPC) has risen dramatically in recent years. We aimed to characterise the clinical and genomic features of EOPC and evaluate their therapeutic implications.

Methods: We performed a comparative, single-centre, retrospective analysis of clinical, germline, and genomic features in EOPC (≤50 years) patients and compared them with a control group of average-onset pancreatic cancer patients (AOPC, ≥70 years). Key molecular findings were compared with an external, publicly available cohort.

Results: We reviewed 336 patients who met all inclusion criteria (EOPC N = 139, AOPC N = 197). EOPC was associated with smoking status, lower prevalence of diabetes, better performance status, higher CA19.9 levels, and higher albumin levels at diagnosis. After adjustment for baseline covariates, we observed no differences in overall survival (OS). Age was associated with an increase in the incidence of KRASMUT both in our cohort and the validation cohort. EOPC were enriched in potentially actionable alterations according to ESCAT tiers I-IIIA when compared with AOPC in discovery and validation cohorts (19% versus 14% and 14% versus 8%, respectively). In the first-line metastatic setting, EOPC had a longer progression-free survival (hazard ratio [HR] 0.61, 95% confidence interval (CI) 0.43-0.87) and OS (HR 0.65, 95% CI 0.45-0.95), although there were no differences in response rate. After adjusting for the number of treatment lines, EOPC patients who did receive targeted therapies exhibited longer OS compared with EOPC who did not (HR 0.34, 95% CI 0.12-0.93).

Conclusions: EOPC patients have improved outcomes in the metastatic setting when compared to AOPC and are enriched for targetable alterations that open opportunities for precision oncology-based approaches.

Keywords: ESCAT alterations; Early-onset pancreatic cancer; Familial pancreatic cancer; Genomic profiling; Precision medicine.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rodrigo Dienstmann reports an advisory role for Roche, Foundation Medicine, received a speaker’s fee from Roche, Ipsen, Amgen, Servier, Sanofi, Libbs, Merck Sharp & Dohme, Lilly, AstraZeneca, Janssen, Takeda, GlaxoSmithKline, Gilead, and research grants from Merck, Novartis, Daiichi-Sankyo, GlaxoSmithKline, and AstraZeneca. Josep Tabernero reports personal financial interest in the form of scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiff Oncology, Chugai, Daiichi-Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, TheraMyc, and Tolremo Therapeutics; Stocks: Oniria Therapeutics and also educational collaboration with Imedex/HMP, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER). Ana Vivancos reports advisory boards from Bayer, Bristol Meyers Squibb, Guardant Health, Incyte, Roche. Stocks or Shares: Reveal Genomics. Research grant, institutional, financial interest, preclinical research grant: Incyte and Roche. Tian V. Tian reports grants from Loxo Oncology at Lilly, Pharmaxis, Incyte, and Alentis, and non-financial support from Servier that are not directly associated with the submitted work. Teresa Macarulla reports personal financial interest in the form of scientific consultancy role for Ability Pharmaceuticals SL, AstraZeneca, Basilea Pharma, Baxter, BioLineRX Ltd, Celgene, Eisai, Incyte, Ipsen Bioscience Inc; speaker’s fee for Janssen and Lilly and direct research funding for MSD, Novocure, QED Therapeutics, Roche Farma, Sanofi-Aventis, Servier, Zymeworks. The remaining authors declare no potential conflicts of interest.

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