Genomic Profiling Linked With Improved Patient Outcomes in Advanced NSCLC

Comprehensive genomic profiling (CGP) in the management of advanced non–small cell lung cancer (NSCLC) was shown to assist in matching patients with targeted therapies and clinical trials with those matched to these therapies associated with improved survival outcomes. Findings were published in BMC Medicine.

Despite the identification of several new targetable drivers in advanced NSCLC, the standard of care for these populations only includes genetic testing for EGFR, ALK, and ROS1 mutations. Notably, previous research shows use of the broader CGP profiling can better assess for emerging mutations, but research regarding its efficacy has not yet been determined.

“Patients carrying alterations other than EGFR, ALK, and ROS1 now have increased access to targeted drugs off label or through a clinical protocol,” said the study authors. “Therefore, a re-evaluation on the clinical implications of CGP in the current treatment landscape of advanced NSCLC is warranted.”

Seeking to further examine the clinical utility of CGP, they prospectively applied the approach to Chinese patients with advanced NSCLC registered in the Precision Medicine Project from October 2016 to October 2019 (N = 1564).

Efficacy of CGP in treatment selection was measured by the proportion of patients receiving a genomic profiling–directed, matched targeted therapy and the proportion of patients being enrolled into a biomarker-selected clinical trial directed by their profiling results.

Those provided with genotype-matched therapy were compared with those who were not matched for progression-free survival (PFS) and overall survival (OS).

In their findings, tumor genomic profiles were established in 1166 participants who underwent CGP:

• Potentially actionable alterations were identified in 781 people (67.0%)
• 37.7% (n = 440) were matched to targeted therapy
• 29.9% (n = 244) were enrolled in genotype-matched trials

Compared with patients with a nonmatched therapy, those who were given genotype-matched therapies showed significant improvements in PFS (9.0 vs 4.9 months; P < .001) and OS (3.9 vs 2.5 years; P < .001).

After excluding patients with standard targeted therapies, genomic profiling led to a matched targeted therapy in 16.7% (n = 24) and a matched trial enrollment in 11.2% (n = 16) of patients. Contrary to that found in the overall cohort, no PFS (4.7 vs 4.6 months; P = .530) or OS (1.9 vs 2.4 years; P = .238) benefit was observed with the use of genotype-matched targeted therapies in these populations.

In concluding, researchers said that given the low likelihood of benefit from the investigational or off-label use of targeted therapies, applicability of genomic profiling results should be taken with caution in patients without standard-of-care drugs.

Reference

Zhao S, Zhang Z, Zhan J, et al. Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer. BMC Med. Published online October 1, 2021. doi:10.1186/s12916-021-02089-z