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30-04-2019 | Non-small cell lung cancer | Highlight | News

Clinicogenomic database yields clinically relevant insights in NSCLC

medwireNews: US researchers have replicated previously described associations between patient and tumor characteristics and clinical outcomes using routinely collected clinical and genomic data for patients with non-small-cell lung cancer (NSCLC).

Gaurav Singal (Foundation Medicine Inc, Cambridge, Massachusetts) and colleagues say that their findings “demonstrate the feasibility of creating a clinicogenomic database derived from routine clinical experience and provide support for further research and discovery evaluating this approach in oncology.”

The researchers created the database by combining electronic health record (EHR)-derived clinical data with comprehensive genomic profiling (CGP) results for 28,998 patients from 275 US oncology practices, including 4064 patients (median age 66 years, 52% women) with NSCLC.

Of the patients with NSCLC, the majority (86.7%) had advanced disease (stage IIIB/IV at diagnosis or recurrent or metastatic disease at any stage), 79.3% had a history of smoking, 77.6% had nonsquamous cancer, and 17.2%, 3.1%, and 1.0% had EGFR, ALK, and ROS1 mutations, respectively.

During 7 years of follow-up, median overall survival (OS) among the patients with advanced disease was 10.3 months, with a 5-year survival rate of 3.8%.

Singal and team found that carriers of TP53 or RB1 mutations had significantly worse median OS than non-carriers (9.6 vs 11.6 months and 8.6 vs 10.4 months, respectively).

The researchers also observed that OS among patients with National Comprehensive Cancer Network (NCCN)-listed driver mutations (EGFR, ALK, ROS1, MET, BRAF, RET, or ERBB2) was significantly better when they received targeted therapies compared with when they did not (18.6 vs 11.4 months).

Consistent with prior reports, EGFR, ALK, and MET alterations were enriched in tumors with nonsquamous pathologies, while patients with EGFR mutations were more likely to be Asian and never smokers.

Also consistent with previous data were the findings that tumor mutational burden (TMB; mutations/Mb) was significantly higher among smokers versus nonsmokers (8.7 vs 2.6) and significantly lower among patients with versus without an alteration in EGFR (3.5 vs 7.8), ALK (2.1 vs 7.0), RET (4.6 vs 7.0), or ROS1 (4.0 vs 7.0).

Furthermore, among patients treated with agents targeting PD-1 or PD-L1, a high TMB (≥20), versus a lower burden, was associated with significantly improved OS from therapy initiation (16.8 vs 8.5 months), longer time receiving therapy (7.8 vs 3.3 months), and a better clinical benefit rate (proportion of patients with stable disease, partial response, or complete response; 80.7 vs 56.7%).

In an editorial accompanying the JAMA study, Ethan Basch (University of North Carolina at Chapel Hill, USA) and Deborah Schrag (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) say that the findings provide “a glimpse at both the well-recognized power of data linkages to evaluate patterns of care and the unrealized potential to accelerate drug discovery.”

However, they caution that most real-world databases lack information on patient quality of life “which is a key component of drug evaluation,” and since understanding “the ‘real’ experience of patients requires information about their symptoms and functioning,” the editorialists believe that future real-world evidence (RWE) sources will need to include patient-reported outcomes to remain relevant.

Basch and Schrag conclude: “Although no drug has yet been approved or received a new indication based on RWE, the ultimate role of this information in drug development remains to be determined.”

By Laura Cowen

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

JAMA 2019; 321: 1359–1360
JAMA 2019; 321: 1391–1399

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