Targeted therapies: How can CT imaging improve evaluations and help understand mechanism of drug action?

Abstract

e13012 Background: We compared the therapeutic response between Varlitinib plus Capecitabine (VC) and Lapatinib plus Capecitabine (LC) by stratifying changes in tumor’s longest diameter (LD) and volume (VOL) per tumor location in patients with HER2+ metastatic breast cancer after trastuzumab therapy. Methods: We retrospectively analyzed the ASLAN001-003 double-arm trial (NCT02338245). We first tested the intra and inter-arm equivalence in number and size of tumors at each location of the disease.Second, we compared the inter-arm average changes in 1) tumor burden according to RECIST; 2) stratified tumor burden in summing, for each patient, the target lesions from the same organ locations; 3) tumors considered independent but grouped per organ location of the disease.Third, we tested the intra-arm differential responses of pairwise groups of tumor locations: breast-lung, breast-liver, breast-lymph nodes, lung-liver, lung-lymph nodes and liver-lymph nodes. A sensitivity analysis tested the robustness of our results. Results: We followed 74 tumors in 35 patients (14 VC; 21 LC) after 12 weeks of treatment. Primary breast tumors had a larger size than metastasis (p < 0.002). Tumor proportions at each organ location of the disease were not significantly different. The inter-arm difference in changes of tumor burden yielded: p = 0.086 (LD) and p = 0.13 (VOL); in stratifying patients per breast tumors: p = 0.002 (LD) and p < 0.001 (VOL); and for independent breast tumors: p = 0.001 (LD) and p < 0.001 (VOL). We found differential responses in the LC arm for breast-liver (p = 0.007 (VOL)) and Liver-Lymph node (p = 0.06 (VOL)). After outlier’s removal, the inter-arm difference was confirmed for breast tumors (p = 0.004 (LD); p < 0.001 (VOL)) and when considering all tumors as independent (p < 0.01(LD); p = 0.04 (VOL)). The differential Breast-Liver response in the VC arm was confirmed p < 0.05 (LD or VOL). Conclusions: Differential imaging responses were found across treatment arms and tumor locations. The stratification of changes provides new insights into responses of targeted therapies and more accurate drug comparisons. The stratification is a promising approach to better understand therapy mechanisms of action behind tumor heterogeneity.