Table 1.
Published articles in PubMed in which liquid biopsy methods are used to guide treatment decisions.
| Alteration | Patients | Platform | Result | References |
|---|---|---|---|---|
| EGFR | 1 | NGS | A rare triple EGFR mutation R670W/H835L/L833V was detected, and the patient responded well on second generation TKIs | (30) |
| Multiple targets | 116 | Guardant 360 | Comprehensive cfDNA testing impacted clinical decisions in 1/4 to 1/3 of initial and subsequent lines of treatment in advanced NSCLC patients. Responses based on cfDNA are durable and change treatment decisions at initial presentation and at progression | (31) |
| EGFR | 52 | ARMS | In the Liquid group, 3 of 4 patients with discordant results between tumor and liquid biopsy showed treatment responses favoring the liquid biopsy | (32) |
| ALK | 1 | ARMS | An EML4-ALK rearrangement was found after acquired resistance to EGFR TKI treatment. Crizotinib was administered. The patient's lung lesions continued to progress after 1 month of crizotinib treatment, and pemetrexed-bevacizumab was initiated. After two cycles of chemotherapy, the metastatic cancers shrunk, and the patient maintained stable disease at his last follow-up | (33) |
| Multiple targets | 50 | dPCR | Patients with both TP53 and EGFR mutations before treatment had worse overall survival than those with only EGFR Patients who progressed without T790M had worse PFS during TKI continuation and developed alternative alterations, including small-cell lung cancer-associated copy number changes and TP53 mutations. Longitudinal plasma analysis can help identify dominant resistance mechanisms, including non-druggable genetic information that may guide clinical management. | (28) |
| EGFR | 119 | ddPCR | Plasma genotyping using digital polymerase chain reaction was clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib | (34) |
| ALK | 1 | NGS | GCC2-ALK was identified and functionally validated as a constitutively activated fusion in NSCLC. The patient benefited from crizotinib treatment initially and then ceritinib after progression, suggesting GCC2-ALK as a novel therapeutic target for ALK inhibitors | (35) |
| EGFR | 1,026 | RT-PCR | Large-scale EGFR testing in the blood of unselected advanced NSCLC patients is feasible and can be used to select patients for targeted therapy when testing cannot be done in tissue. The characteristics and clinical outcomes to TKI treatment of the EGFR-mutated patients identified are undistinguishable from those positive in tumor. | (15) |
| EGFR | 3 | Three cases are presented that were successfully treated with osimertinib after progression on 1st and 2nd generation EGFR TKIs. The presence of T790M mutation was detected from ctDNA of the patients | (36) | |
| EGFR | 1 | Without histological analysis, the origin of the primary ocular metastasis was uncertain. In this context, a LB showing an activating mutation in EGFR and circulating tumor cells positive for TTF1 led to the diagnosis of NSCLC and targeted therapy | (37) | |
| EGFR | 18 | dPCR | Monitoring levels of EGFR mutation in plasma allows resolving doubts that frequently arise in daily clinical practice and constitutes a major step toward achieving personalized medicine | (12) |
| ALK | 1 | FoundationACT | Here we report an ALK+ NSCLC patient who had disease progression after ceritinib and then alectinib where an ALK G1202R mutation was detected on ctDNA prior to enrollment onto a trial of another next generation ALK inhibitor, lorlatinib. The patient's central nervous system (CNS) metastases responded to lorlatinib together with clearance of ALK G1202R mutation by repeat ctDNA assay. However, the patient developed a new large pericardial effusion. Resected pericardium from the pericardial window revealed SCLC transformation with positive immunostaining for synaptophysin, chromogranin, and ALK (D5F3 antibody) | (38) |
| EGFR | 48 | NGS | The ctDNA T790M mutation was detected in 50% of NSCLC patients. Among assessable patients, osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5% | (39, 40) |
| Multiple targets | 68 | NGS | Over 80% of patients had detectable ctDNA, concordance between paired tissue and blood for truncal oncogenic drivers was high and patients with biomarkers identified in plasma had PFS in the expected range | (26) |
| EGFR | 1 | A novel urine ctDNA assay was utilized and confirmed T790M positive status. The patient was started on a third generation TKI, which led to a measurable clinical response | (41) |
The search was conducted on September 1, 2018 using the keyword “NSCLC liquid biopsy.”