Introduction: KRAS mutation is the most frequent molecular alteration found in advanced NSCLC; it is associated with a poor prognosis without available targeted therapy. Treatment options for NSCLC have been recently enriched by the development of immune checkpoint inhibitors (ICIs), and data about its efficacy in patients with KRAS-mutant NSCLC are discordant. This study assessed the routine efficacy of ICIs in advanced KRAS-mutant NSCLC. Methods: In this retrospective study, clinical data were extracted from the medical records of patients with advanced NSCLC treated with ICIs and with available molecular analysis between April 2013 and June 2017. Analysis of programmed death ligand 1 (PD-L1) expression was performed if exploitable tumor material was available. Results: A total of 282 patients with ICI-treated (in the first line or more) advanced NSCLC (all histological subgroups) who were treated with ICIs (anti-programmed death 1, anti-PD-L1, or anti-cytotoxic T-lymphocyte associated protein 4 antibodies), including 162 (57.4%) with KRAS mutation, 27 (9.6%) with other mutations, and 93 (33%) with a wild-type phenotype, were identified. PD-L1 analysis was available for 128 patients (45.4%), of whom 45.3% and 19.5% had PD-L1 expression of 1% or more and 50%, respectively (49.5% and 21.2%, respectively, in the case of the 85 patients with KRAS-mutant NSCLC). No significant difference was seen in terms of objective response rates, progression-free survival, or overall survival between KRAS-mutant NSCLC and other NSCLC. No significant differences in overall survival or progressionfree survival were observed between the major KRAS mutation subtypes (G12A, G12C, G12D, G12V, and G13C). In KRAS-mutant NSCLC, unlike in non-KRAS-mutant NSCLC, the efficacy of ICIs is consistently higher, even though not statistically significant, for patients with PD-L1 expression in 1% or more of tumor cells than for those

Background: A significant gap in pancreatic ductal adenocarcinoma (PDAC) patient's care is the lack of molecular parameters characterizing tumours and allowing a personalized treatment. Methods: Patient-derived xenografts (PDX) were obtained from 76 consecutive PDAC and classified according to their histology into five groups. A PDAC molecular gradient (PAMG) was constructed from PDX transcriptomes recapitulating the five histological groups along a continuous gradient. The prognostic and predictive value for PMAG was evaluated in: i/ two independent series (n = 598) of resected tumours; ii/ 60 advanced tumours obtained by diagnostic EUS-guided biopsy needle flushing and iii/ on 28 biopsies from mFOLFIRI-NOX treated metastatic tumours. Findings: A unique transcriptomic signature (PAGM) was generated with significant and independent prognostic value. PAMG significantly improves the characterization of PDAC heterogeneity compared to non-overlapping classifications as validated in 4 independent series of tumours (e.g. 308 consecutive resected PDAC, uHR=0.321 95% CI [0.207À0.5] and 60 locally-advanced or metastatic PDAC, uHR=0.308 95% CI [0.113À0.836]). The PAMG signature is also associated with progression under mFOLFIRINOX treatment (Pearson correlation to tumour response: -0.67, p-value < 0.001). Interpretation: PAMG unify all PDAC pre-existing classifications inducing a shift in the actual paradigm of binary classifications towards a better characterization in a gradient.