2017P - Comprehensive molecular profiling of small cell lung cancer patients treated with chemo-immunotherapy or chemotherapy alone

Background

Small cell lung cancer (SCLC) is one of the most lethal forms of lung cancer, with a 5-year survival rate of approximately 7%. SCLC has been divided into limited stage (LS) and extensive stage (ES). For ES-SCLC the use of immunotherapy (IO) has been introduced in combination with platinum-based chemotherapy (CT), prolonging the overall survival of patients. However, only a small fraction of patients experience a durable clinical benefit from this approach, with no selection criteria able to predict clinical outcome. Here we hypothesize that different mutational profiles could be associated to clinical outcome of patients treated with CT-IO with respect to CT alone.

Methods

A case series of 88 ES-SCLC patients was enrolled. Tumor tissues of patients were analysed with a next-generation sequencing-based assay (Foundation One CDx), analysing 324 genes, selected gene rearrangements, microsatellite instability (MSI) and tumor mutational burden (TMB). Statistical analyses have been performed to study the correlation among clinical characteristics, mutational profiles and clinical outcome has been performed.

Results

For patients with available clinical information, 36 were treated with CT-IO and 50 with CT alone. The 65% of patients were male, and the 35% were female, median age was 71 (range 50-86) years old. The 36.2% of patients were former smokers whereas 53.75% were current smokers, while smoking habits were not available for 16 patients. The most frequently mutated genes were TP53 (98%), RB1 (80%), MLL2 (35%), NOTCH3 (16.2%), MLL (12.5%), RICTOR (8.8%), CDKN2A/B (7.3%), APC (7.3%), MYC (6.3%) and MYCL1 (6.3%). No rearrangements were detected in any patient. With regard to TMB, 25% of patients had low TMB (<6 mut/Mb), 65% of patients had intermediate TMB (6>20 mut/Mb), and 10% of patients had high TMB (>20 mut/Mb). MSI data was available for 67 patients, and all but one patients were stable. Survival analyses and correlation of clinical outcome with mutational profiles are still ongoing.

Conclusions

Our results suggest that a comprehensive genomic profile could help to predict clinical outcome of ES-SCLC patients treated with CT-IO.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.