Original ArticleCo-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

- Role of co-clinical studies in precision cancer medicine is increasingly recognized.
- This study compared tumor volume in co-clinical trials of ALK-rearranged NSCLC.
- Similarities and differences of tumor volume changes in mice and humans were noted.
- The study provides insights to optimize murine co-clinical trial designs.

PurposeTo 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).MethodsVolumetric 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.ResultsThe 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.ConclusionThe 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.