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Kiyotaka Yoh



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    OA03 - Advances in Lung Cancer Pathology (ID 897)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 205 BD
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      OA03.02 - Nationwide Comparative Study Of PD-L1 IHC Assays on Lung Cancer: Initial Report Of LC-SCRUM-IBIS Project (ID 11321)

      10:40 - 10:50  |  Author(s): Kiyotaka Yoh

      • Abstract
      • Presentation
      • Slides

      Background

      Precision medicine requires accurate biomarkers for appropriate therapeutic decision. PD-L1 IHC is a predictive biomarker for immune checkpoint inhibitor (ICI), however, the complexity of PD-L1 IHC system could make interpretations confusion in practice. In this study, we compared four PD-L1 IHC systems using real-world clinical samples to reveal their properties and capability of harmonization as a part of nationwide immuno-oncology biomarker study of lung cancer (LC-SCRUM-IBIS).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Out of 1635 lung cancer patients enrolled in LC-SCRUM-Japan, four PD-L1 IHC assays (22C3, 28-8, SP263 and SP142) and whole-exome sequencing (WES) were analyzed in addition to NGS mutation screening by the Oncomine™ Comprehensive Assay (OCA). Planned accrual is 1000. IHC was evaluated by three certified lung pathologists independently. Three-tier scoring system (cutoff value of 1, 50%) applied for tumor cell (TC) in all assays, and TC+IC scoring algorism in SP142, according to the manufactural instruction. We calculated Spearman’s correlation coefficient and kappa value among TC proportion and the original protocol’s criteria of each assays. Discordant rate among assays was examined.

      4c3880bb027f159e801041b1021e88e8 Result

      486 patients (438 nonsmall, 48 small cell carcinoma) completed IHC study analysis from February to December 2017.

      Compared to 22C3, TC-score of 28-8 (kappa value 0.896) were and SP263 (0.729) showed good, and SP142 resulted slight (0.159) correlations. SP142-tc+ic score showed fair correlation with 22C3/28-8/SP263 TC-scores (kappa= 0.213/ 0.241/ 0.291, respectively).

      Our results showed substantial reproducibility of TC score among observers across different IHC assays (range of kappa: 0.675 – 0.837). Inter-observer concordance of the SP142-IC score was also acceptable (kappa 0.591-0.779). Of note, within 22C3 positive group (>1%), 4.5/15.6/67.7/55.0 % of 28-8/SP263/SP142-tc/SP142-(tc+ic) resulted in negative, respectively, indicating a risk of lower category switching for SP263 and SP142 compared to 22C3 and 28-8. A subset (8.3%) of 22C3-negative group resulted in SP142-positive and all such discrepancy was due to IC-positivity.

      There was no significant association between each PD-L1 expression and TMB by WES and OCA. Out of 77 patients treated with ICI, most responders (11/17, 65%) had PD-L1 high expression.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results revealed an excellent/moderate/slight correlation between 22C3 and 28-8/SP263/SP142. SP142-positive-cases were fewer and more rigorous than the other three assays. A subset of lung cancer showed IC-only PD-L1-positivity. Inter-observer reproducibility was substantial for TC and moderate for IC. The scoring algorism affected concordance trend in a modest way. For harmonization, we should aware of each assays properties. PD-L1 IHC is not a perfect but a feasible biomarker for patients’ selection of ICI therapy.

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-33 - Randomized Phase 2 Study Comparing CBDCA+PTX+BEV and CDDP+PEM+BEV in Treatment-Naïve Advanced Non-Sq NSCLC (CLEAR study) (ID 12448)

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

      • Abstract
      • Slides

      Background

      Bevacizumab (BEV) combined with platinum-based chemotherapy is a standard treatment for advanced non-squamous non-small-cell lung cancer (non-Sq NSCLC). Cisplatin (CDDP) + pemetrexed (PEM) is suggested as the most promising chemotherapy regimen combined with BEV. However, no study has been conducted to evaluate the efficacy and safety of CDDP+PEM+BEV compared with carboplatin (CBDCA) + paclitaxel (PTX) + BEV for advanced non-Sq NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Treatment-naïve patients with advanced or recurrent EGFR/ALK-negative non-Sq NSCLC from 55 sites across Japan were randomly assigned in a 2:1 ratio to either CDDP+PEM+BEV (4 cycles of CDDP [75 mg/m2] + PEM [500 mg/m2] + BEV [15 mg/kg] q3wk, followed by maintenance PEM + BEV q3wk until progression) or CBDCA+PTX+BEV (4 cycles of CBDCA [AUC 6] + PTX [200 mg/m2] + BEV q3wk, followed by maintenance BEV q3wk until progression). The primary endpoint was progression-free survival (PFS) by central review. The secondary endpoints were PFS by investigators, overall survival (OS), overall response rate (ORR) and safety profile. The target numbers of patients and events were determined to be 210 and 170, respectively, to observe a point estimate of HR for PFS (CDDP+PEM+BEV/CBDCA+PTX+BEV) <0.83 with a high probability (80%) when the true HR was 0.72.

      4c3880bb027f159e801041b1021e88e8 Result

      Between May 2014 and May 2016, 199 patients were randomly assigned to receive CDDP+PEM+BEV (N=132) or CBDCA+PTX+BEV (N=67). The median follow-up duration was 20.6 months. PFS events occurred in 171 patients. The HR for PFS by central review (CDDP+PEM+BEV/CBDCA+PTX+BEV) was 0.825 (95% CI 0.600-1.134, median PFS, 7.6 vs 7.0 months). The median PFS by investigators was longer with CDDP+PEM+BEV than with CBDCA+PTX+BEV (HR 0.634, 95% CI 0.464-0.867, median PFS, 7.4 vs 6.8 months). The median OS was 24.5 months for CDDP+PEM+BEV and 23.6 months for CBDCA+PTX+BEV (HR 0.955, 95% CI 0.620-1.470). The ORR was 57% for CDDP+PEM+BEV and 55% for CBDCA+PTX+BEV. The most common ≥G3 adverse events in both arms (CDDP+PEM+BEV/CBDCA+PTX+BEV) were neutropenia (24%/64%), hyponatraemia (11%/9%) and hypertension (30%/23%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      CDDP+PEM is the most effective chemotherapy regimen combined with BEV for advanced non-Sq NSCLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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