Assessment of objective responses in thymic epithelial tumors using ITMIG modified criteria.

OBJECTIVES: Pleural metastases of thymic epithelial tumors (TETs) are relatively common, and this unique growth pattern makes the use of RECIST (response evaluation criteria in solid tumors) response criteria difficult. To standardize tumor measurement in TETs, the International Thymic Malignancy Interest Group (ITMIG) has proposed newly developed criteria. We compared evaluation of objective response between ITMIG modified criteria and RECIST 1.1 in patients with TET treated with systemic chemotherapy. PATIENTS AND METHODS: We retrospectively evaluated the tumor response of 40 patients with unresectable TET who were enrolled in a phase II clinical trial using ITMIG modified criteria, and compared the findings with prospectively evaluated tumor response assessed by RECIST 1.1. Agreement analyses for the response at each time point, including overall response and declaring progression, were performed and the time to progression (TTP) was also assessed using the two different measurements. RESULTS: The overall response rate assessed by the two methods did not differ significantly, with kappa value of 0.897. Agreement analysis for declaring progression of disease (PD) at the date of RECIST 1.1-designated PD showed 95% concordance rate with ITMIG modified criteria (p=1.000, kappa index=0.875). The median TTP according to RECIST 1.1 and ITMIG modified criteria was 8.4 and 7.9 months (p=0.983), respectively. Validation with another cohort of 27 TET patients treated with neoadjuvant chemotherapy also showed a 96% concordance rate in overall response between the two different criteria. CONCLUSIONS: ITMIG modified criteria showed a high concordance rate with RECIST 1.1 criteria in response assessment of TETs. Given the rarity of TETs, further evaluation of ITMIG modified criteria in a larger number of patients will be required before their implementation in clinical trials.

Assessment of EGFR Mutation Status in Matched Plasma and Tumor Tissue of NSCLC Patients from a Phase I Study of Rociletinib (CO-1686).

PURPOSE: The evaluation of plasma testing for the EGFR resistance mutation T790M in NSCLC patients has not been broadly explored. We investigated the detection of EGFR activating and T790M mutations in matched tumor tissue and plasma, mostly from patients with acquired resistance to first-generation EGFR inhibitors. EXPERIMENTAL DESIGN: Samples were obtained from two studies, an observational study and a phase I trial of rociletinib, a mutant-selective inhibitor of EGFR that targets both activating mutations and T790M. Plasma testing was performed with the cobas EGFR plasma test and BEAMing. RESULTS: The positive percent agreement (PPA) between cobas plasma and tumor results was 73% (55/75) for activating mutations and 64% (21/33) for T790M. The PPA between BEAMing plasma and tumor results was 82% (49/60) for activating mutations and 73% (33/45) for T790M. Presence of extrathoracic (M1b) versus intrathoracic (M1a/M0) disease was found to be strongly associated with ability to identify EGFR mutations in plasma (P < 0.001). Rociletinib objective response rates (ORR) were 52% [95% confidence interval (CI), 31 - 74%] for cobas tumor T790M-positive and 44% (95% CI, 25 - 63%) for BEAMing plasma T790M-positive patients. A drop in plasma-mutant EGFR levels to ≤10 molecules/mL was seen by day 21 of treatment in 7 of 8 patients with documented partial response. CONCLUSIONS: These findings suggest the cobas and BEAMing plasma tests can be useful tools for noninvasive assessment and monitoring of the T790M resistance mutation in NSCLC, and could complement tumor testing by identifying T790M mutations missed because of tumor heterogeneity or biopsy inadequacy. Clin Cancer Res; 22(10); 2386-95. ©2016 AACR.