This pooled analysis was designed to evaluate the correlation between extent of ALK FISH positivity and efficacy of crizotinib among patients with non–small cell lung cancer. ALK-positivity above 15% was associated with crizotinib response.
In clinical trials of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treated with crizotinib, evaluation of the relationship between the percentage of ALK-positive cells by fluorescence in situ hybridization (FISH)—particularly near the cutoff defining positive status—and clinical outcomes have been limited by small sample sizes.
Of 11 081 screened patients, 1958 (18%) were ALK-positive, 7512 (68%) were ALK-negative, and 1540 (14%) were uninformative. Median percentage of ALK-positive cells was 58% in ALK-positive patients and 2% in ALK-negative patients. Of ALK-positive patients, 5% had 15–19% ALK-positive cells; of ALK-negative patients, 2% had 10 − 14% ALK-positive cells. Objective response rate for ALK-positive, crizotinib-treated patients with ≥20% ALK-positive cells was 56% (n=700/1246), 55% (n=725/1312) for those with ≥15% ALK-positive cells, and 38% for those with 15–19% ALK-positive cells (n=25/66). As a continuous variable, higher percentages of ALK-positive cells were estimated to be associated with larger differences in objective response and PFS between crizotinib and chemotherapy; however, tests for interaction between treatment and percentage of ALK-positive cells were not significant (objective response, P=0.054; PFS, P=0.17).
http://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.9062
