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S. Nakamichi



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    P1.09 - Poster Session 1 - Combined Modality (ID 212)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P1.09-010 - Impact of the presence of EGFR mutation on the definitive chemoradiotherapy in patients with locally advanced non-small cell lung cancer: pattern of relapses and survival analyses in 198 patients (ID 1227)

      09:30 - 16:30  |  Author(s): S. Nakamichi

      • Abstract

      Background
      The epidermal growth factor receptor (EGFR) mutational status is an important biomarker in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the frequency and clinical significance of EGFR mutation in patients with potentially curable locally advanced NSCLC (LA-NSCLC) who are eligible for definitive chemoradiotherapy (CRT).

      Methods
      Between Jan 2001 and Dec 2010, we conducted analysis for the presence of EGFR mutations, in consecutive non-squamous NSCLC (mainly in adenocarcinoma) patients who were eligible for CRT. The response rate (RR), progression-free survival (PFS), 2-year progression-free rate, first recurrent sites, and overall survival were investigated according to the EGFR mutational status.

      Results
      A total of 528 patients received CRT at the National Cancer Center Hospital during the study period, of which 274 were diagnosed as having non-squamous NSCLC (mainly adenocarcinoma). Sufficient specimens for mutational analyses could be obtained from 198 patients, and EGFR mutations were found at a frequency of 17% in these patients. In addition to the well-known characteristics of NSCLC patients carrying EGFR mutations (female, adenocarcinoma, and never/light smoker), the proportion of cases with smaller (T1/2) primary lesions was also higher in the patients carrying mutated EGFR than in those carrying wild-type EGFR. Patients carrying mutated EGFR showed similar RR (79% vs. 76%), median PFS (11.8 m vs. 10.6 m) and 2-year progression-free survival rate (22% vs. 30%) as compared to those carrying wild-type EGFR. Local recurrence as first relapse occurred less frequently in patients carrying mutated EGFR than in those carrying wild-type EGFR (4% vs. 21%). A majority of the patients with mutated EGFR showing disease progression received EGFR-TKIs (55%), and these patients showed a longer post-progression survival and a higher 5 year survival rate (50% vs. 34%) than the patients with wild-type EGFR.

      Conclusion
      Among the LA-NSCLC patients eligible for definitive CRT who were included in this analysis, 17% harbored EGFR-activating mutations in the carcinoma specimens. Although definitive CRT was similarly effective in both patients with mutated EGFR and wild-type EGFR, substantially lower frequency of local relapse was noted in the patients carrying mutated EGFR. Among the LA-NSCLC patients harboring EGFR mutations who developed disease progression, those treated with EGFR-TKIs showed a longer post-progression survival and overall survival as compared to those who did not receive EGFR-TKIs.

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    P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.11-012 - Phase Ia/Ib study of the anti-MET antibody onartuzumab (MetMAb) in patients with solid tumors or MET-positive lung cancer (ID 1164)

      09:30 - 16:30  |  Author(s): S. Nakamichi

      • Abstract

      Background
      MET, a receptor tyrosine kinase, and its ligand, hepatocyte growth factor (HGF), play a key role in cancer progression and prognosis. Aberrant activation of the HGF/MET pathway can enhance invasion, proliferation, and survival of cancer cells, providing a rationale for developing therapeutics that block MET activation. Onartuzumab was engineered as a unique recombinant humanized one-armed anti-MET monoclonal antibody that inhibits HGF-induced MET signaling without agonistic activity.

      Methods
      This 2-stage study was the first in Japanese patients to evaluate efficacy, safety, and pharmacokinetics (PK) of onartuzumab or onartuzumab in combination with erlotinib. In Stage 1—a 3+3 dose-escalation stage—patients with advanced solid tumors, refractory to the standard of care or for which there is no standard of care, received onartuzumab at doses of 4, 15, or 30 mg/kg IV once every 3 weeks until disease progression. In Stage 2—a combination stage—onartuzumab at a dose of 15 mg/kg IV once every 3 weeks was given in combination with erlotinib 150 mg/day to patients with advanced MET-positive non–small-cell lung cancer who had received at least 1 prior platinum-containing regimen (as regards EGFR-TKI, only 1 regimen was permitted); this regimen was continued until disease progression. Exploratory biomarker analyses were also conducted.

      Results
      In Stage 1, 9 patients (male/female: 6/3) were enrolled. Median age was 68 years. There were no dose-limiting toxicities (DLTs) and the maximum tolerated dose was not reached at 30 mg/kg. Hypoalbuminemia (33.3%) and constipation (33.3%) were the most frequent adverse events (AEs). Hypoalbuminemia was the only AE occurring at grade 3 severity, indicating that onartuzumab was well tolerated up to 30 mg/kg. In Stage 2, 6 patients were enrolled (male/female: 1/5; adeno/squamous: 5/1; EGFR wild type/mutant: 3/3; median age 69 years). There were no DLTs. The most frequent AE was diarrhea (83.3%). Grade 1/2 AEs occurred in all patients. There was one grade 3 case of each of deep vein thrombosis, pulmonary embolism, rash, hypoxia, dermatitis acneform, diarrhea, and neutropenia. No grade 4/5 AE was observed. PK analysis from patients in Stages 1 and 2 indicated dose proportionality of C~max~ and AUC. No drug–drug interaction between onartuzumab and erlotinib was observed. In Stage 2, progression-free survival was beyond 6 months in 2 patients (7.2 and 12.2 months); 1 patient achieved a partial response. Median circulating HGF concentration after onartuzumab was elevated to approximately three times the baseline level.

      Conclusion
      Onartuzumab alone or with erlotinib was well tolerated in Japanese patients. The PK profile of onartuzumab was not affected by co-administration with erlotinib.