Co-clinical Quantitative Tumor Volume Imaging in ALK-rearranged NSCLC Treated with Crizotinib

Citation:

Nishino M, Sacher AG, Gandhi L, Chen Z, Akbay E, Fedorov A, Westin CF, Hatabu H, Johnson BE, Hammerman P, et al. Co-clinical Quantitative Tumor Volume Imaging in ALK-rearranged NSCLC Treated with Crizotinib. Eur J Radiol. 2017;88 :15-20. Copy at http://www.tinyurl.com/yckhkv4n

Date Published:

2017 Mar

Abstract:

PURPOSE: To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC). METHODS: Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans. RESULTS: The median tumor volume decrease (%) at the maximal response was -40.4% (range: -79.5%-+11.7%) in mice, and -72.9% (range: -100%-+72%) in humans (Wilcoxon p=0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months. CONCLUSION: The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.

Last updated on 07/13/2017