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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

4780 - Identification of genomic markers of sensitivity and resistance to checkpoint inhibitors in non-small cell lung cancer in a real world clinico-genomic database

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Karthikeyan Murugesan

Citation

Annals of Oncology (2018) 29 (suppl_8): viii493-viii547. 10.1093/annonc/mdy292

Authors

K. Murugesan, G. Li, G. Kaushik, G. Singal, V.A. Miller, G.M. Frampton, L.A. Albacker

Author affiliations

  • Cancer Genomics, Foundation Medicine, Inc., 02141 - Cambridge/US
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Resources

Abstract 4780

Background

Treatment of non-small cell lung cancer (NSCLC) with checkpoint inhibitors (CI) that block the PD-L1 pathway has resulted in profound responses but only in a subset of patients. Our aim was to examine biomarkers associated with response and resistance to CI in advanced NSCLC to help inform patient stratification.

Methods

We examined 820 lung adenocarcinoma (LUAD) samples that had matched PD-L1 staining and received genomic profiling to measure tumor mutational burden (TMB) and genomic alterations in 315 genes (FM cohort). We also examined progression free survival (PFS) of 1310 CI treated patients in a HIPAA compliant, real world clinicogenomic database (CGDB). These patients received the FoundationOne assay as part of routine care and had electronic health record data available in the Flatiron Health Database (Singal, ASCO 2017).

Results

In the CGDB, we observed known associations between likelihood of PFS and TMB, loss of STK11. TMB correlated with median PFS in months (mPFS): TMB > 20 mutations per MB (N = 164) – 6 mo vs TMB < =20 (N = 1146) – 2.8 mo, P = 1e-07). Patients with STK11 loss had reduced mPFS (wt 3.1 mo vs mut 2.5 mo, P = 0.01). We analyzed PDL1 staining for driver alterations in LUADs in the FM cohort. EGFR mutant samples were enriched for PDL1 negative staining (FM cohort: P = 6.3e-5) and the EGFR cohort had reduced mPFS (CGDB: wt 3 mo vs mut 2.4 mo, P = 0.003). Samples with MET exon 14 skipping mutations were enriched for PDL1 high positive staining (FM: P = 2.3e-5), but the MET cohort had similar mPFS (CGDB: wt 3 mo vs mut 2.7 mo, P = 0.8). Samples with BRAF alterations trended towards both PDL1 high positive staining (FM: P = 0.06) and increased mPFS (CGDB: wt 2.9 mo vs mut 4.6 mo, P = 0.2).

Conclusions

We examined PFS of NSCLC patients on CI therapies in a clinicogenomic database and observed known associations with TMB, STK11 and EGFR alterations. We found that, at a population level, MET altered patients did not have enhanced mPFS despite increased PDL1 HP staining, suggesting dual or targeted therapies. Real-world datasets such as the CGDB hold promise in prioritizing therapies and identifying biomarkers of response and resistance.

Clinical trial identification

Legal entity responsible for the study

Foundation Medicine Inc., Cambridge, Massachusetts, United States of America.

Funding

Foundation Medicine Inc., Cambridge, Massachusetts, United States of America.

Editorial Acknowledgement

Disclosure

K. Murugesan, G. Li, G. Kaushik, G. Singal, V.A. Miller, L.A. Albacker, G.M. Frampton: Employee: Foundation Medicine Inc.

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