Background:

Targeted molecular therapy and immunotherapy have revolutionized the treatment of advanced lung cancer (ALC). Although therapeutically significant, the outcome of immune checkpoint inhibitors (ICI) or tyrosine kinase inhibitors (TKI) depends on the presence of their respective targets in tumor cells. Evaluating targets based on solid tissue biopsy may often be misleading, particularly in progressive patients despite therapy administration. Additionally, tissue biopsy provides a static signature of target protein expression from an evolving tumor. The unmet need for dynamic detection and monitoring of actionable targets could be addressed by circulating tumor cells (CTCs). Here, we report on the utility of CTCs to detect actionable targets in advanced lung cancer (ALC) patients.

Methods:

We retrospectively analyzed 193 ALC patients for programmed death-ligand 1 (PD-L1) and EGFR expression on CTCs. CTCs were isolated using the Drug Controller General of India-approved OncoDiscover technology based on immunomagnetic targeting using anti-EpCAM antibodies and immunostaining with anti-EGFR and PD-L1 antibodies. CTCs were detected based on the expression of cytokeratins (CKs), absence of CD45, and prominent DAPI-stained nuclei. The presence or absence of EGFR and PD-L1 was determined using automated immunofluorescence microscopy.

Results:

Among the evaluated cohort, 67% of patients showed the presence of CTCs with a mean value of 4.2 (range: 1 to 62; SD = 10.65). The absence of CTCs in the remaining 33% of patients could be attributed to therapy response in clinically stable disease. Among all patients showing the presence of CTCs, 66% showed detectable expression of PD-L1, while 42% showed strong expression of EGFR. The presence of PD-L1 demonstrated a significant association with CTCs. Similarly, the expression of EGFR among detected CTCs showed high significance compared to reported tissue biopsy data in the literature.

Conclusions:

Detection of therapeutic targets on CTCs obtained from advanced lung cancer patients strongly indicates that these patients may qualify for anti-EGFR and PD-L1 targeted therapies. Systematic studies with larger sample sizes are required to further strengthen liquid biopsy–based detection of actionable targets. This approach could significantly benefit advanced lung cancer patients showing progressive disease despite chemotherapy or radiotherapy.