Virtual Library

Start Your Search

Kiyotaka Yoh



Author of

  • +

    OA02 - Novel Therapies in ROS1, HER2 and EGFR (ID 893)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 105
    • +

      OA02.07 - Updated Results of Phase 1 Study of DS-8201a in HER2-Expressing or –Mutated Advanced Non-Small-Cell Lung Cancer (ID 13325)

      11:35 - 11:45  |  Author(s): Kiyotaka Yoh

      • Abstract
      • Presentation
      • Slides

      Background

      DS-8201a is a HER2-targeting antibody-drug conjugate with a novel peptide-based cleavable linker, a topoisomerase I inhibitor payload, and a high drug-to-antibody ratio (7 to 8). In preclinical studies, DS-8201a showed broad antitumor activity, in a wide range of tumors. The ongoing phase 1 trial has a dose-escalation (part 1) and -expansion (part 2) and includes subjects with advanced breast cancer, gastric cancer, and other HER2-expressing/-mutated solid tumors. Here, we present updated results for subjects with HER2-expressing or -mutated non-small cell lung cancer (NSCLC).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Subjects with HER2-expressing (defined as IHC ≥1+ or amplified) or –mutated (detected by NGS or other platforms) NSCLC were eligible to enroll. HER2 expression and mutation were assessed using archival tissue. Adverse events (AEs), objective response rate (ORR), disease control rate (DCR: CR + PR + SD), and duration of response (DOR) were assessed.

      4c3880bb027f159e801041b1021e88e8 Result

      [Results will be updated for presentation at meeting] As of Apr 18, 2018, 12 subjects with HER2-expressing and/or -mutated NSCLC received ≥1 dose of DS-8201a at 6.4 mg/kg. Median age was 58.5 y with median of 3 prior regimens. At data cutoff, 8 of 12 (66.7%) subjects remain on treatment. HER2 IHC status was available for 7 subjects. Median duration of treatment was 3.66 months (range 0.69, 14.19). Eight of 10 (80.0%) subjects with ≥1 post-baseline scan (ps) experienced tumor shrinkage (100.0% of them at 1st ps at 6 weeks). Overall, confirmed ORR and DCR in the evaluable subjects was 5 of 8 (62.5%) and 6 of 8 (75.0%), respectively. Among subjects with HER2 IHC 2+ or IHC 3+ expression, 2 of 5 (40.0%) had a PR. Overall, median DOR was 11.5 months (range 0.03+, 11.53). Three of 12 (25.0%) subjects experienced a grade ≥3 AE. Common AEs included decreased appetite 66.7% (0.0% grade ≥3), nausea 58.3% (0.0% grade ≥3), alopecia 41.7% (0.0% grade ≥3), and fatigue 41.7% (0.0% grade ≥3). One fatal case of interstitial lung disease was reported in this subgroup.

      8eea62084ca7e541d918e823422bd82e Conclusion

      DS-8201a demonstrated promising antitumor activity in heavily pretreated NSCLC subjects.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.09 - Pathology (Not CME Accredited Session) (ID 941)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.09-33 - Validity of Non-Small Cell Lung Cancer Not Otherwise Specified to Use Immunohistochemistry on Treatment Outcome (ID 11190)

      16:45 - 18:00  |  Author(s): Kiyotaka Yoh

      • Abstract

      Background

      In non-small cell lung cancer, histologic samples have become significantly important to administrate tumor type specific cytotoxic and molecular-targeted therapies. When a biopsy sample shows lacking definite morphology, diagnosis is made into three subtypes, favour adenocarcinoma, favour squamous cell carcinoma and NOS-null, according to the immunohistochemistry (IHC) results. However, in terms of the patient outcome, validity of IHC-based these classification have been unknown yet.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A series of 152 advanced NSCLC patients whose diagnosis was made by morphology and homogeneously treated was enrolled. We performed IHC staining (TTF-1, SP-A, p40, and CK5/6) of these samples and refined diagnoses into 3 subtypes. We analyzed the pathological subgroup depends on IHC staining with clinical characteristics including molecular analysis, response of chemotherapy and prognosis.

      4c3880bb027f159e801041b1021e88e8 Result

      IHC profiling displayed that 50% of cases was favour Ad, 31% was favour SqCC, and 19% was NOS-null. On the patient background, there was no difference in age, smoking history, and PS, but there were differences in gender, and the favour Ad group had more females than other groups. EGFR mutation was significantly more expressed in favour Ad group than in the other groups, and molecular targeted drugs in initial treatment were used in favour Ad group in a large proportion. Compared with favour Ad and SqCC group, NOS-null group showed significantly poorer outcome in terms of median overall survival (OS). Between favour Ad and favour SqCC group, median OS was better in favour Ad group (19.5 months vs 15.0 months, p = 0.018). Excluding patients using molecular targeted drugs, there was no difference in median OS between favour Ad and favour SqCC group (15.2 months vs 15.0 months p = 0.29). Pemetrexed containing platinum regimen showed similar response rate as other platinum regimen in the favour Ad cohort (43% vs 46%), whereas poorer response in the favour SqCC (0% vs 50%) and NOS-null (0% vs 24%) cohort. Although patients to be received pemetrexed containing platinum regimen compared to those to be received other platinum regimen demonstrated a trend toward good PFS in favour Ad group, there were no statistically differences.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study made clear chemo-responsiveness, the expression frequency of driver mutation and prognosis in NSCLC favour Ad, SqCC and NOS-null. These findings support that histological subtyping in biopsy specimen by IHC would be mandatory to archive appropriate therapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53