Patients with ALK-rearranged non-small cell lung cancer (NSCLC) who are treated with crizotinib may experience increased progression-free survival (PFS) with a decrease in a type of circulating tumor cells, according to research published in Cancer Research (May 2017;77[9]:2222).
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Approval of crizotinib as an ALK-targeted therapy has vastly improved outcomes for patients with ALK-rearranged NSCLC. However, the duration and magnitude of clinical response to crizotinib in such patients is unpredictable.
French researchers led by Françoise Farace, PhD, conducted a study to evaluate whether circulating tumor cells with aberrant ALK-rearrangement, ALK-copy number gain patterns monitored on crizotinib could predict PFS in patients with ALK-rearranged NSCLC. A total of 39 patients were prospectively recruited and underwent blood samples at baseline and 2 months after initiating crizotinib treatment.
Researchers analyzed the samples for ALK rearrangements and for increases in the number of copies of the ALK gene. All patients were reported to have both circulating tumor cells with ALK rearrangements and ALK copy number gain at the time of both blood samples.
Results of the analysis showed no significant association between baseline circulating tumor cells and PFS. However, an association was found between the decrease in circulating tumor cells with ALK-copy number gain on crizotinib and a longer PFS (P = .025). Median PFS for the patients who had a decrease in circulating tumor cells with ALK-copy number gain (n = 13) was 14.0 months, whereas median PFS for the patients who had stable or increased circulating tumor cells with ALK-copy number gain (n = 16) was 6.1 months.
An additional multivariate showed that the dynamic change of circulating tumor cells with ALK-copy number gain was the strongest correlating factor associated with PFS (HR, 4.49; 95% CI, 1.54-13.03; P = .006).
"In this study, we showed that analysis of ALK copy number in circulating tumor cells before starting crizotinib treatment and after 2 months of crizotinib treatment may provide a biomarker for predicting the effectiveness of the [therapy]," said Dr Farace in a press release (May 1, 2017). "This is important because there is currently no means of distinguishing those patients likely to gain long-term benefit from crizotinib from those who are not and who should consider trying some of the newer ALK-targeted therapeutics that have been more recently developed.”
Further validation in larger studies at different sites are needed before these findings can be used in a clinical setting. Nonetheless, this study demonstrates the ability of liquid biopsies to monitor treatment responses in real-time. — Zachary Bessette
