Liquid Biopsy Equivalent to Tissue in Guiding Treatment of NSCLC

Hai T. Tran, PharmD

Hai T. Tran, PharmD

A matched retrospective comparison showed that progression-free survival (PFS) in patients with advanced non—small cell lung cancer (NSCLC) and actionable mutations was similar whether treatment was guided by the use of tissue biopsy or circulating tumor DNA (ctDNA) analysis with the Guardant360 assay.

In separate 40-patient subgroups, the median PFS was 379 days with tissue-guided treatment and 352 days with blood-based genomic profiling. An analysis of 122 matched cases showed no difference in sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), or diagnostic accuracy between genomic analysis of tissue specimens versus ctDNA.

“This is the largest retrospective analysis of response rates with ctDNA-directed therapy in advanced NSCLC and demonstrates positive clinical outcomes in patients treated with targeted therapy based on plasma-identified biomarkers,” Hai T. Tran, PharmD, of the University of Texas MD Anderson Cancer Center, and colleagues reported in a poster presentation at the 2019 World Lung Cancer Conference.

“ctDNA next-generation sequencing (NGS) can become a significant clinical tool in several situations such as when a rapid molecular result is needed, repeat invasive tissue biopsy is not possible, or tissue sample is not available or inadequate for complete molecular analysis.”

NGS of ctDNA has become widely available at CLIA-approved laboratories and is used for noninvasive genomic profiling of cancer. Limited comparative data have accumulated regarding the clinical outcomes associated with tissue-based and ctDNA genomic analyses. Tran and colleagues hypothesized that the two techniques would lead to similar outcomes.

Investigators analyzed data from 2354 blood samples obtained from 2100 patients with newly diagnosed advanced NSCLC during 2015 to 2017. Each sample was analyzed by means of a 68 to 73 cancer-gene panel (Guardant360) that included single nucleotide variants, insertion-deletion and fusion alterations, and copy number amplifications.

Identification of targetable molecular alterations led directly to treatments based on FDA approvals, National Comprehensive Cancer Network guidelines for targeted agents, or potential eligibility for clinical research trials.

Baseline characteristics of the 2100 patients showed a median age of 66, that women accounted for 51.2% of the study population, and adenocarcinoma histology in 85.9% of cases.

The ctDNA analysis identified any type of molecular alteration in 87.3% of the blood samples and 1 or more targetable alterations in 595 (25.3%) samples from 341 patients. The most commonly identified targetable mutation wasEGFRexon del19 in 156 tests, EGFR L858Rin 110, EGFR/ERBB2exon 20 insertion in 91, and EGFRexon del19 + T790M in 55. Overall, some type of EGFRvariant accounted for 81% of the identified abnormalities.

Investigators matched a subgroup of 40 patients who underwent ctDNA analysis with 40 patients who had genomic analysis of tissue specimens. Women accounted for 45 of the 80 patients, who had a median age of about 60.EGFRexon del19 was identified in about half of the patients andL85Rin 34 of the 80, with even distribution between the 2 groups.

The 27-day difference in median PFS between the 2 groups did not reach statistical significance (P= .420).

The comparison of targetable mutations identified by ctDNA and tissue in 122 matched cases showed strong agreement between the 2 testing techniques. The overall diagnostic accuracy was 99.6% and was 100% for 8 of 11 types of targetable mutations identified. Sensitivity was 99.2%, specificity 99.7%, PPV 96.7%, and NPV 99.9%.

Reference:

Tran H, Lam V, Vasquez M, et al. Outcomes in advanced NSCLC patients treated with 1st line EGFR-TKI based on mutation detection from tissue or cfDNA-based genomic sequencing. Presented at: IASLC 20th World Conference on Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract P1.01-98.