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. 2022 Jul 8;29(7):4811-4826.
doi: 10.3390/curroncol29070382.

Real-World Clinical Outcomes after Genomic Profiling of Circulating Tumor DNA in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer

Steven Olsen  1 , Jiemin Liao  2 , Hidetoshi Hayashi  3
Affiliations

Real-World Clinical Outcomes after Genomic Profiling of Circulating Tumor DNA in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer

Steven Olsen et al. Curr Oncol. .

Abstract

Comprehensive genomic profiling for advanced non-small cell lung cancer (NSCLC) can identify patients for molecularly targeted therapies that improve clinical outcomes. We analyzed data from 3084 patients (median age 65 years, 72.9% with adenocarcinoma) with advanced NSCLC registered in a real-world healthcare claims database (GuardantINFORMTM, Guardant Health) who underwent next-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) testing (Guardant360®, Guardant Health) after first-line therapy (28.0% with agents targeted against genomic alterations). ctDNA was detected in 2771 samples (89.9%), of which 41.9% harbored actionable alterations, most commonly EGFR (epidermal growth factor receptor) mutations (29.7%). Actionable alterations were detected in 26.7% of patients (534/2001) previously treated with non-targeted agents. Emerging potentially targetable mutations were found in 40.1% (309/770) of patients previously treated with targeted therapies. Among patients with qualifying alterations detected by ctDNA testing, the time to treatment discontinuation (median 8.8 vs. 4.2 months; hazard ratio 1.97, p < 0.001) and overall survival (median 36.1 vs. 16.6 months; hazard ratio 2.08, p < 0.001) were longer for those who received matched second-line therapy versus unmatched second-line therapy. In real-world practice, results of a blood-based NGS assay prior to second-line treatment inform therapeutic decisions that can improve clinical outcomes for patients with advanced NSCLC.

Keywords: actionable alterations; comprehensive genomic profiling; ctDNA; non-small cell lung cancer; targeted therapy.

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Conflict of interest statement

S.O. is an employee of Guardant Health, Inc., and holds stock in Guardant Health, Inc and AstraZeneca. J.L. is an employee of Guardant Health, Inc. H.H. reports grants from AstraZeneca K.K., Bristol-Myers Squibb Co. Ltd. Boehringer Ingelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., and Ono Pharmaceutical Co. Ltd. and personal fees from AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., Guardant Health, Inc., Kyorin Pharmaceutical Co. Ltd., Merck Biopharma Co. Ltd., MSD K.K., Novartis Pharmaceuticals K.K., Ono Pharmaceutical Co. Ltd., Shanghai Haihe Biopharm, Taiho Pharmaceutical Co. Ltd., Pfizer, and Takeda Pharmaceutical Co. Ltd.

Figures

Figure 1
Figure 1
Time to discontinuation of second-line treatment (A) and overall survival (B) after ctDNA testing according to whether first-line treatment was targeted or non-targeted. CI, confidence interval; HR, hazard ratio; TTD, time to treatment discontinuation; OS, overall survival; Ref, reference.
Figure 2
Figure 2
Time to discontinuation of second-line treatment (A) and overall survival (B) after ctDNA testing in the four patient cohorts, irrespective of the class of first-line treatment received. CI, confidence interval; HR, hazard ratio; TTD, time to treatment discontinuation; OS, overall survival; Ref, reference.
Figure 3
Figure 3
Time to discontinuation of second-line treatment in the four patient cohorts according to whether the first-line therapy was non-targeted (A) or targeted (B). CI, confidence interval; HR, hazard ratio; TTD, time to treatment discontinuation; Ref, reference.
Figure 4
Figure 4
Overall survival after second-line ctDNA testing in the four patient cohorts according to whether the first-line therapy was non-targeted (A) or targeted (B). CI, confidence interval; HR, hazard ratio; NR, not reached; OS, overall survival; Ref, reference.
See this image and copyright information in PMC

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