Onset of CT scan morphological changes in metastatic lesions and associated responses in gastric patients treated with telatinib.

Abstract

81 Background: Response to the antiangiogenic agent, bevacizumab, by CT has been associated with a unique morphologic change in liver metastasis (mets) where heterogeneous attenuation, variable degree of enhancement and ill-defined borders before treatment transform into homogeneous, hypoattenuating lesions with well defined borders, mimicking a cyst. CT-based morphologic criteria in colorectal cancer (CRC) had a statistically significant association with pathologic response and overall survival, (Chun, JAMA 2009). The CT changes likely reflect the replacement of mets by fibroconnective tissue rather than tumor necrosis. Telatinib (tel) is a novel orally available kinase inhibitor that is highly selective for the VEGFR, PDGFR, and KIT tyrosine kinases at nanomolar concentrations with potent antiangiogenic activity. Methods: TEL0805, a Phase 2 study administered tel with capecitabine (X) and cisplatin (P) in previously untreated metastatic or unresectable gastric or GEJ adenocarcinoma pts. Response assessments were every 2 cycles (6 weeks). The ORR in response evaluable pts was 69% (1 CR, 21 PR in 32 pts). CT films from 16/32 response evaluable pts were analyzed and reviewed by a radiologist at a single institution, 10 pts had liver mets. Results: The median onset of response was 49 days. CT changes of mets at week 6 scans included: decreased attenuation and/or a sharp interface with rapid reduction of mets (n=6); mixed response, with decreased attenuation but persistent borders, and/or slight increase in mets followed by onset of response week 12 (n=3), and PD (n=1). CT changes correlate with durable responses. Conclusions: Telatinib + XP produces rapid onset of tumor response with morphologic CT changes in gastric cancer liver mets similar to those observed in CRC pts with bevacizumab, consistent with antiangiogenic activity. Further analyses in a randomized setting to correlate CT morphologic response with survival are planned. [Table: see text]