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Kenichi Yoshimura



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    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-45 - Cisplatin Plus Gemcitabine Therapy Followed by Maintenance Gemcitabine for Advanced Squamous Cell Lung Cancer (KTORG1302) (Now Available) (ID 514)

      08:00 - 18:00  |  Author(s): Kenichi Yoshimura

      • Abstract
      • Slides

      Background

      One of the standard treatments in chemo-naïve patients with advanced non-small cell lung cancer (NSCLC) is platinum-containing doublet chemotherapy. Moreover non-squamous NSCLC, patients benefit from pemetrexed maintenance therapy following induction therapy with cisplatin (CDDP) plus pemetrexed. However, no large-scale trial showing the efficacy of maintenance therapy has been reported in squamous cell lung cancer. We evaluated the efficacy and the safety of continuation maintenance therapy with gemcitabine (GEM) after induction chemotherapy with CDDP plus GEM in advanced squamous cell lung cancer.

      Method

      This study was a single-arm, multicenter and phase II trial. Main eligibility criteria included Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1, and the aged of 20 to 74 years old. Patients received an induction phase which consisted of 4 cycles of CDDP (80mg/m2, day 1, q3w) plus GEM (1000mg/m2, day 1, 8, q3w). Patients who did not progress after completion of 4 cycles of induction received continuation maintenance therapy with GEM (1000mg/m2, day 1, 8, q3w) until disease progression. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population.

      Result

      Between June 2013 and October 2018, 26 patients were enrolled in this study. Although the scheduled numbers were 60, this study was ended early for poor accrual.

      The mean age was 65.7 years (range, 47 – 74 years). 18 patients (69.2%) completed 4 cycles of CDDP plus GEM, and 16 patients (61.5%) received continuation maintenance therapy with GEM. At the cutoff date of December 31, 2018, overall response rate was 46.2%, median PFS from induction therapy was 5.3 months (95% confidence interval [CI]: 2.9-7.3), and median PFS from continuation maintenance therapy was 3.8 months (95% CI: 2.3-5.2). Median overall survival from induction therapy was 11.9 months (95% CI: 7.5-26.5). The most common grade 4 adverse events were neutropenia (16%) and thrombocytopenia (12%). Pneumonitis ware seen in 3 cases (grade 1: 1, grade 2: 1, grade 3: 1 case). Adverse events except for hematotoxicity were generally well tolerated. There were no treatment-related deaths.

      Conclusion

      This study terminated early because of poor accrual and did not meet its primary endpoint. However, this study indicated continuation maintenance therapy with GEM can be well-tolerated treatment option for patients with advanced squamous NSCLC.

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    OA02 - A New Vision of Targets and Strategies (ID 120)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
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      OA02.01 - Alectinib in Previously Treated RET-Rearranged Advanced Non-Small-Cell Lung Cancer: A Phase 1/2 Trial (ALL-RET) (Now Available) (ID 1651)

      10:30 - 12:00  |  Author(s): Kenichi Yoshimura

      • Abstract
      • Presentation
      • Slides

      Background

      RET rearrangements occur in 1–2% of non-small cell lung cancers (NSCLCs). Alectinib (300 mg twice daily) has been approved for the treatment of ALK-rearranged NSCLC in Japan; it also has a high activity against RET in vitro. A global trial (ALEX study) showed the efficacy and safety of alectinib (600 mg twice daily) in ALK-rearranged NSCLC patients. We conducted a phase 1/2 study of alectinib to establish the recommended dose (RD) and examined its activity in RET-rearranged Japanese NSCLC patients.

      Method

      This study was a single-arm, open-label, multi-institutional phase 1/2 trial. RET-rearranged NSCLC patients treated with at least one regimen of chemotherapy were recruited. RET rearrangements were screened using LC-SCRUM-Japan, a nationwide genomic screening network. In phase 1, alectinib (600 or 450 mg twice daily) was administered, following a 3 + 3 design. The primary endpoint was safety. During phase 2, alectinib at the RD defined in phase 1 was administered. The primary endpoint was the objective response rate in RET inhibitor-naïve patients.

      Result

      Between March 8, 2016 and January 29, 2018, 35 patients were enrolled, and 34 patients were administered alectinib. KIF5B-RET was the most common fusion gene (22 cases [63%]), and the CCDC6-RET fusion was identified in 8 cases. The remaining 5 cases were not distinguishable. In cohort 1 (600 mg twice daily), we observed 5 DLTs (grade 3 rash, increased aspartate aminotransferase, erythema multiforme, thromboembolic event, and increased CPK) in 3 of 6 patients. In accordance with the protocol, we moved to cohort 2 (450 mg twice daily) and observed no DLTs in 3 patients. Additionally, pharmacokinetic analysis indicated that the mean exposure (AUC0–10) of 600 mg twice daily was higher than that previously reported in AF-002JG trial (global phase 1 study). Therefore, we determined 450 mg twice daily as the RD for phase 2. Twenty-five RET inhibitor-naïve patients were treated with the RD, of whom 1 achieved an objective response (4%) and 13 achieved disease control at 8 weeks (52%) as determined by central review. The median progression-free survival was 3.4 months (95% CI 2.0-5.4), and the median overall survival was 19.0 months (5.4-NE). We observed grade 3 neutropenia, pneumonitis, diarrhea, hyponatremia, increased CPK and blood bilirubin (4%) in patients treated with 450 mg alectinib twice daily; no grade 4 adverse events were observed.

      Conclusion

      Alectinib had limited activity in patients with RET-rearranged NSCLC. Further investigation of new targeted therapeutics is required to improve outcomes for these patients.

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