Pancreatic adenocarcinoma third line systemic treatments: a retrospective cohort study.

BACKGROUND: Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) primarily relies on FOLFIRINOX (LV5FU- irinotecan - Oxaliplatine) and Gemcitabine - Nab-Paclitaxel in the first-line setting. However, second-lines remain less well-defined and there is limited data regarding third-line treatments. The objective of our study was to determine the proportion of patients advancing to third line chemotherapy, to outline the various third-line chemotherapy regimens used in routine practice and to evaluate their respective efficacy. METHODS: A retrospective single-center cohort from 2010-2022 compiled baseline characteristics, treatment outcomes and survival of PDAC patients who received at least one chemotherapy line in a French tertiary-center. Overall survivals (OS) were analyzed using a Cox multivariable model. RESULTS: In total, 676 patients were included, with a median follow-up time of 69.4 months, (Interquartile Range (IQR) = 72.1). Of these, 251 patients (37%) that proceeded to 3rd-line chemotherapy. The median PFS in 3rd line was 2.03 months, [CI95%: 1.83, 2.36]. The median 3rd line overall survival was 5.5 months, [CI95%: 4.8, 6.3]. In multivariable analysis erlotinib-based chemotherapy was found to be deleterious (HR=2.38, [CI95%: 1.30, 4.34], p=0.005) compared to fluoropyrimidine-based chemotherapy in terms of 3rd line overall survival while gemcitabine monotherapy showed a tendency towards negative outcomes. First and 2nd line chemotherapies sequence didn't influence 3rd line outcome. CONCLUSION: In our cohort, one-third of treated patients proceeded to 3rd line chemotherapy resulting in a 5.5 months median 3rd line OS, consistent with treatments at advanced stage. Our results argue against the use of erlotinib and gemcitabine monotherapy.

Pancreatic cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up

The opportunity to detect pancreatic cancer (PC) when potentially curable depends on early diagnosis and an ability to identify and screen high-risk populations before symptoms arise. Identification of a high-risk population is challenging and optimal screening tools remain unclear.1 Older age is the strongest risk factor; incidence peaks at 65-69 years in males and 75-79 years in females.2 A pooled analysis of 117 meta-analyses assigned a relative risk to a number of common risk factors (Supplementary Table S1, available at https://doi.org/10.1016/j.annonc.2023.08.009).3 The vast majority (>80%) of PCs arise due to sporadically occurring somatic mutations. Only a small proportion are due to inherited deleterious germline mutations.1 Familial PC, defined as at least two first-degree relatives with PC, accounts for only 4%-10% of all cases. Variants in BRCA2 are the most common genetic abnormalities seen in familial PC. Other familial syndromes linked to PC are listed in Supplementary Table S2, available at https://doi.org/10.1016/j.annonc.2023.08.009. Individuals from families at risk should receive genetic counselling and be considered for enrolment in investigational screening registries. Currently, in high-risk individuals, annual endoscopic ultrasound (EUS) and/or pancreatic magnetic resonance imaging (MRI) are the procedures of choice for surveillance.4 Surveillance programmes usually begin at age 50 years (or 10 years earlier than the age of the youngest affected relative). Prospective surveillance data in high-risk individuals demonstrated high rates of resectability and encouraging observations of long-term survival.5, 6, 7, 8, 9 In sporadic PC, the major risk factors are tobacco, Helicobacter pylori infection and factors related to dietary habits (high red meat, high alcohol intake, low fruit and vegetable intake, overweight/obesity and type 2 diabetes mellitus).2,3,10 Chronic pancreatitis, irrespective of the cause (alcohol abuse, smoking, genetic mutations), is a risk factor for PC. A proportion of the risk factors associated with PC are potentially modifiable, affording a unique opportunity for primary prevention that is yet to be realised.