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Yu Jung Kim



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    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.01-60 - Prognostic Impact of PD-L1 Expression on EGFR Tyrosine Kinase Inhibition in Lung Adenocarcinoma (ID 1506)

      09:45 - 18:00  |  Author(s): Yu Jung Kim

      • Abstract
      • Slides

      Background

      EGFR tyrosine kinase inhibitors (TKIs) are recommended as first-line systemic therapy for advanced non-small cell lung cancer (NSCLC) with sensitizing EGFR mutations. The programmed death-ligand 1 (PD-L1) expression on tumor cells has emerged as a prognostic marker after surgical resection in various tumors including NSCLC. This study investigated the predictive value of PD-L1 expression on the duration of treatment and the emergence of T790M mutation in patients treated with EGFR-TKIs.

      Method

      We retrospectively enrolled 109 patients with advanced NSCLC who had been treated with EGFR-TKIs as first-line systemic treatment at Seoul National University Bundang Hospital and Seoul National University Hospital between December 2012 and October 2018. Patients without sensitizing EGFR gene mutations (exon 19 deletion, exon 21 L858R, and L861Q) were excluded. The PD-L1 expression on tumor cells was scored using two immunohistochemistry assays (22C3 or SP263). The Kaplan-Meier survival estimation and log rank test were used for survival analyses.

      Result

      Among the 109 patients (Median age 65; Male:Female = 37:72), 17 (15.6%), 37 (33.9%) and 55 (50.5%) patients had strong (≥50%), weak (1%-49%), and negative (<1%) PD-L1 expression, respectively. In univariate analysis, the median time-to-treatment failure (TTF) of EGFR-TKI treatment was 7.6 months in strong expression, 14.2 months in weak expression, and 13.0 months in negative expression (log-rank; Strong vs. Weak, P=0.008; Strong vs. Negative, P=0.031). There was no statistically significant difference of TTF between the patients with weak expression and negative expression (log-rank, p=0.191). After adjustment of age, sex, and smoking status, strong PD-L1 expression remained as a significant predictor of short TTF (hazard ratio [HR] for strong vs. weak, 2.68; 95% CI, 1.35-5.33; P=0.005). The detection rates of T790M mutation after EGFR-TKI failure were similar in three groups (23.53% in strong, 29.73% in weak, and 32.73% in negative PD-L1 expression; P=0.478). In patients treated with 3rd generation EGFR-TKIs (n=35), there was no statistically significant difference of TTF according to PD-L1 expression (p=0.889).

      Figure. Kaplan-Meier survival curve for TTF of 1st line EGFR-TKIs according to PD-L1 expression

      figure.jpg

      Conclusion

      Strong PD-L1 expression of tumor might be a surrogate indicator of poor response to EGFR-TKIs in NSCLC patients with sensitizing EGFR mutations.

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    PL02 - Presidential Symposium including Top 7 Rated Abstracts (ID 89)

    • Event: WCLC 2019
    • Type: Plenary Session
    • Track:
    • Presentations: 1
    • Now Available
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      PL02.08 - Registrational Results of LIBRETTO-001: A Phase 1/2 Trial of LOXO-292 in Patients with RET Fusion-Positive Lung Cancers (Now Available) (ID 964)

      08:00 - 10:15  |  Author(s): Yu Jung Kim

      • Abstract
      • Presentation
      • Slides

      Background

      No targeted therapy is currently approved for patients with RET fusion-positive non-small cell lung cancer (NSCLC). LOXO-292 is a highly selective RET inhibitor with activity against diverse RET fusions, activating RET mutations and brain metastases. Based on initial data from LIBRETTO-001, LOXO-292 received FDA Breakthrough Designation for the treatment of RET fusion-positive NSCLC in August 2018.

      Method

      This global phase 1/2 study (87 sites, 16 countries) enrolled patients with advanced RET-altered solid tumors including RET fusion-positive NSCLC (NCT03157128). LOXO-292 was dosed orally in 28-day cycles. The phase 1 portion established the MTD/RP2D (160 mg BID). The phase 2 portion enrolled patients to one of six cohorts based on tumor type, RET alteration, and prior therapies. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints included DoR, CNS ORR, CNS DoR, PFS, OS, safety and PK.

      Result

      As of 17-June 2019, 253 RET fusion-positive NSCLC patients were treated. The primary analysis set (PAS) for LOXO-292 registration, as defined with the US FDA, consists of the first 105 consecutively enrolled RET fusion-positive NSCLC patients who received prior platinum-based chemotherapy; 58 patients (55%) also received prior anti PD-1/PD-L1 agents. The majority of PAS responders have been followed for ≥6 months from first response. Of the remaining 148 patients, 79 had previously been treated with platinum-based chemotherapy, 55 did not receive prior platinum-based chemotherapy and 14 did not have measurable disease at baseline.

      Among PAS patients, the investigator-assessed ORR was 68% (95% CI 58-76%, n=71/105, 2 PRs pending confirmation). Responses did not differ by fusion partner or the type or number of prior therapies, including chemotherapy, anti PD-1/PD-L1 agents and multikinase inhibitors with anti-RET activity. The median DoR was 20.3 months (95% CI 13.8-24.0) with a median follow-up of 8 months; as evidenced by the wide confidence interval, this DoR estimate is not statistically stable due to a low number of events (16 of 69 confirmed responders). The intracranial ORR was 91% (n=10/11: 2 confirmed CRs, 8 confirmed PRs) for patients with measurable brain metastases at baseline.

      The ORR in efficacy evaluable treatment naïve RET fusion-positive NSCLC patients was 85% (95% CI 69-95%, n=29/34, 7 PRs pending confirmation). In the safety data set of all 531 patients, 5 treatment-related AEs occurred in ≥15% of patients: dry mouth, diarrhea, hypertension, increased AST and increased ALT. Most AEs were grade 1-2. Only 9 of 531 (1.7%) patients discontinued LOXO-292 for treatment-related AEs.

      Conclusion

      LOXO-292 had marked antitumor activity in RET fusion-positive NSCLC patients and was well tolerated. These data will form the basis of an FDA NDA submission later this year.

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