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I. Okamoto



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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-010 - Survival outcome assessed by response and tumor shrinkage pattern in non-small cell lung cancer patients with activating mutations of the epidermal growth factor receptor (ID 752)

      09:30 - 09:30  |  Author(s): I. Okamoto

      • Abstract

      Background
      Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with the dramatic therapeutic response to EGFR-tyrosine kinase inhibitors (TKIs) in patients with advanced non–small cell lung cancer (NSCLC); however, there are no studies investigating clinical indicators that affect the likelihood of survival benefit from EGFR-TKI in selected patients with EGFR mutations. We evaluated the progression-free survival (PFS) and overall survival (OS) according to response and tumor shrinkage pattern among EGFR-mutated NSCLC.

      Methods
      Among 145 EGFR-mutation positive patients treated with EGFR-TKI, 68 patients were selected for the present analysis.

      Results
      Of those 68 patients, six patients achieved complete response (CR), 42 patients partial response (PR), and 14 patients stable disease (SD). The PFS and OS of CR/PR group was significantly longer than that of the SD group. A multivariate analysis demonstrated that response (CR/PR) to EGFR-TKI significantly correlated with both PFS and OS. Among CR/PR group, the median maximum tumor change from baseline was -56%, and the median time to response (TTR) was 4.2 weeks. No trend toward more favorable PFS and OS benefit was seen in the subset of patients who had experienced rapid tumor regression (TTR < 4.2 weeks) as well as high degree of tumor shrinkage (< -56%) compared with those who showed slow tumor regression (TTR > 4.2 weeks), or low degree of tumor shrinkage (> -56%) among CR/PR patients.

      Conclusion
      Response (CR/PR) may represent the optimal surrogate for efficacy among EGFR mutation-positive patients treated with EGFR-TKI patients.

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    P2.14 - Poster Session 2 - Mesothelioma (ID 196)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
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      P2.14-003 - Phase I and pharmacokinetic study of amatuximab, a novel chimeric antibody to mesothelin, in patients with advanced solid tumors (ID 1209)

      09:30 - 09:30  |  Author(s): I. Okamoto

      • Abstract

      Background
      Amatuximab is a chimeric monoclonal antibody to mesothelin. Mesothelin, a membrane protein, is a potential target for molecular targeted therapy due to its high expressions in virtually all pancreatic cancers and mesotheliomas as well as several cancers, while showing little expression in normal tissues, except for normal mesothelium. Amatuximab inhibits the growth of mesothelin-expressing human tumors in vitro and in vivo xenograft model.

      Methods
      To investigate dose-limiting toxicities (DLTs) and estimate the maximum tolerated dose (MTD) of amatuximab in Japanese patients with advanced solid tumors. In addition, pharmacokinetics of amatuximab, human anti-chimeric antibody (HACA) and mesothelin expression by immunohistochemistry (IHC) were investigated. Patients with pancreatic cancers, mesotheliomas, or mesothelin-positive solid tumors as assessed by the IHC test, who have no other appropriate treatment were eligible in the study. Amatuximab was administered weekly until disease progression or occurrence of a DLT, and administered to 3 cohorts at 50, 100 and 200 mg/m[2] in a step-wise dose escalation manner. The pharmacokinetic parameters were calculated by model independent analysis and the dose proportionality was investigated on Cmax and AUC (0-t) values.

      Results
      58 patients were screened and a total of 17 patients were enrolled consisting of seven colorectal cancer, six pancreatic adenocarcinoma, two mesothelioma and two head and neck cancer (seven patients in 50 mg/m[2], three in 100 mg/m[2] and seven in 200 mg/m[2], respectively). Two DLTs were observed (grade 3 cytokine release syndrome in 50 mg/m[2] and grade 5 interstitial lung disease in 200 mg/m[2]). Treatment related adverse events were observed in 13 of 17 patients, and the most common events were grade 1 fatigue (five patients) and pyrexia (four patients). Amatuximab was eliminated from serum biphasically after reached Cmax. Estimated mean T1/2 on Cycle 1 Day 1 was 92.3 to 108 h and CL was 11.7 to 15.2 mL/h/m[2]. It was found that the Cmax and AUC (0-t) values on Cycle 1 Day 1 increased in an almost dose proportional manner and these were similar to those in US patients. HACA was detected in eight of 17 patients. Of 53 patients whose tissue samples were evaluated by IHC, 24 patients (45.3%) were mesothelin-positive (10 of 19 patients in colorectal cancer, four of eight in biliary cancer, four of five in pancreatic adenocarcinoma and six of 21 in other cancers).

      Conclusion
      Amatuximab was well tolerated in patients with advanced solid tumors, and MTD was not reached up to 200 mg/m[2]. Pharmacokinetic profile of amatuximab in Japanese patients was similar to that in US patients. Amatuximab is currently being investigated for its potential treatment of mesothelioma.