Clinical Outcomes after Whole Genome Sequencing in Patients with Metastatic Non-Small Cell Lung Cancer.

BACKGROUND: The Personalized OncoGenomics (POG) program at the British Columbia Cancer Agency integrates whole genome (DNA) and RNA sequencing into practice for metastatic malignancies. We examined the subgroup of patients with metastatic non-small cell lung cancer (NSCLC) and report the prevalence of actionable targets, treatments, and outcomes.

METHODS: We identified patients who were enrolled in the POG program between 2012-2016 who had a tumor biopsy and blood samples with comprehensive DNA (80X;40X normal) and RNA sequencing followed by in-depth bioinformatics to identify potential cancer drivers and actionable targets. In NSCLC cases, we compared the progression-free survival (PFS) of "POG-informed therapies" with the PFS of the last regimen prior to POG (PFS ratio).

RESULTS: In 29 NSCLC cases, median age was 60.2 years (range 39.4-72.6). 11 were male (38%), and histologies were: adenocarcinoma (93%), squamous cell carcinoma (7%). Potential molecular targets (i.e. cancer drivers including TP53 mutations) were identified in 26 (90%), and 21 (72%) had actionable targets. Therapies based on standard-of-care mutation analysis, such as EGFR mutations, were not considered POG-informed therapies. 13 received POG-informed therapies, of which 3 had no therapy before POG therefore a comparator PFS could not be obtained. Of 10 patients with POG-informed therapy, median PFS ratio was 0.94 (IQR 0.2-3.4). 3 (30%) had a PFS ratio ≥1.3, and 3 (30%) had a PFS ratio ≥0.8 and <1.3.

CONCLUSION: In this small cohort of NSCLC, 30% demonstrated longer PFS with POG-informed therapies. Larger studies will help clarify the role of whole genome analysis in clinical practice.