Circulating Tumor Cells May Predict Lung Cancer Response to Crizotinib

It may soon be possible to predict which patients with non–small-cell lung cancer (NSCLC) fueled by anaplastic lymphoma kinase (ALK) gene alterations and treated with crizotinib will do better than others. French researchers are reporting in the journal Cancer Research that an analysis of ALK copy number in circulating tumor cells (CTCs) before starting crizotinib treatment and after 2 months of crizotinib treatment may provide a biomarker for predicting the effectiveness of the drug.

The researchers prospectively recruited 39 patients with ALK-rearranged NSCLC. All the patients had a blood draw prior to starting crizotinib treatment. Blood samples were taken about 2 months later for 29 of these patients. The team found that a decrease in the number of CTCs harboring increased copies of the ALK gene over the first 2 months of treatment was associated with increased progression-free survival (PFS). 

Analysis of CTC numbers at the different time points showed that the one measurement that was statistically significantly associated with PFS was a change in the number of CTCs with ALK copy number gain over time. Median PFS was 14 months for the 13 patients who had a decrease in the number of CTCs. The median PFS was 6.1 months for the 16 patients who had stable or increased numbers of CTCs. In multivariate analysis, patients who had a decrease in the number of CTCs were 4.5 times less likely to experience disease progression compared with those who had stable or increased numbers of CTCs.

“The approval of the ALK-targeted therapeutic crizotinib has improved outcomes for patients with ALK-rearranged NSCLC, but the duration of responses varies widely, from a few months to several years,” said study investigator Françoise Farace, PhD, leader of the circulating cells team at Gustave Roussy, INSERM, Université Paris-Saclay, Villejuif, France.

Farace said these findings are clinically significant because currently there is no means of distinguishing those patients likely to gain long-term benefit from crizotinib from those who will not benefit. Identifying patients early who are not responsive to treatment could lead to improved outcomes. Clinicians could in a more timely fashion switch patients to one of the newer ALK-targeted therapeutics that have been recently developed, according to Farace.

She said this is a proof-of-concept study that warrants validation with larger studies at multiple sites. If validated, it could lead to liquid biopsies for monitoring treatment response in real time.