Abstract 1117P
Background
Large cell neuroendocrine lung carcinoma (LCNEC) is an aggressive subtype with an incidence around 3% of all lung cancer. The treatment approach for advanced patients remains controversial due to the lack of large randomized trials including this subtype. Owing to this fact, molecular characterization using next generation sequencing (NGS) technology has become a key tool for the molecular profiling of LCNEC.
Methods
We performed a retrospective analysis of 55 patients with LCNEC treated in our institution from 2011 to 2020. Clinical characteristics and molecular alterations were described. Different NGS platforms were used.
Results
Of 55 patients analyzed, NGS was performed in 25 (tissue NGS in 52%, blood based NGS in 24% patients, both in 24%). Up to 71% of patients were male and all of them heavy smokers. The initial stage diagnosis was III for 22,6% and stage IV for 55% of patients. Most cases were pure large cell neuroendocrine tumors (87%), followed by combined histology with adenocarcinoma (13%). 49 % of patients had KI- 67 labeling index ≥ 50 %. PD-L1 status using IHC 22C3 pharmDx was performed in 59% of tumor samples (PD-L1<1% 56,6 %, PD-L1 1-49% 26,6% PDL1≥50% 16,6%). Tumor mutational burden was ≥10 mut/Mb) in 3 out of 4 patients evaluated. TP53 mutation was the most common molecular finding (52%). From the 11 patients with TP53 wild type, 9 had mutations in other genes (45.4% KRAS, 9% FGFR-1, 9% ERBB-2, 9% PI3K and 9% RET rearrangement), stablishing a hypothetical higher dependance on oncogenic activation. Moreover, mutations in SWI/SNF chromatin-remodeling complexes were also detected (SMARCA4 8% and ARID1A 8%). Other mutations were detected in 14 patients (56%): KRAS (32%), EGFR (8%), BRAF (4%), ERBB2 (4%), BRCA1 (4%) and DDR2 (4%), with potential clinical significance.
Conclusions
Comprehensive molecular tumour profiling allows to identify specific mutations which can be targeted by approved treatments or by new drugs under development in clinical trials in order to improve the poor prognosis of these patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
P. Garrido Lopez: Financial Interests, Personal, Advisory Board: abbvie; Financial Interests, Personal, Advisory Board: amgen; Financial Interests, Personal, Invited Speaker: astrazeneca; Financial Interests, Personal, Advisory Board: bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker, Spouse: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Gebro; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board, Spouse: Nordic; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Institutional, Other, Local PI: Apollomics; Financial Interests, Institutional, Other, Local PI: Array Biopharma; Financial Interests, Institutional, Other, Local PI: Blue Print; Non-Financial Interests, Leadership Role, Member of the Scientific Committee of the Spanish Against Cancer Research Foundation (aecc) and also Borad member: AECC; Non-Financial Interests, Leadership Role, Council member as Women for Oncology Committee Chair Fellowship and Award Committee and Press Committe Faculty for lung and other thoracic tumours: ESMO; Non-Financial Interests, Leadership Role, President of the Spanish Federation of Medical Societies (FACME): FACME; Non-Financial Interests, Leadership Role, IASLC Women in Thoracic Oncology Working Group Member: IASCL; Non-Financial Interests, Leadership Role, Former President of Spanish Medical Oncology Society Member of the Spanish National Health Advisory Board: SEOM. All other authors have declared no conflicts of interest.