Author of

• 32148

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  EP1.14 - Targeted Therapy (ID 204)

  • Event: WCLC 2019
  • Type: E-Poster Viewing in the Exhibit Hall
  • Track: Targeted Therapy
  • Presentations: 1
  • Now Available
  • Moderators:
  • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall

  • 32209

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    EP1.14-49 - A Phase IIIb Open-Label Study of Afatinib in EGFR TKI-Naïve Patients with EGFRm+ NSCLC: Exploratory Biomarker Analysis (Now Available) (ID 1265)

    08:00 - 18:00  |  Author(s): Zhiyi Xue
    • Abstract
    • Slides

    Background
    

    The safety and efficacy of EGFR TKIs in patients with EGFR mutation-positive (EGFRm+) NSCLC have previously been demonstrated. Here, we present results of a biomarker analysis from a subset of patients in a Phase IIIb study of afatinib in EGFR TKI-naïve patients with locally advanced/metastatic EGFRm+ NSCLC. The aim was to explore the relationship between tumor mutation type, and patients’ response to afatinib in terms of efficacy and tolerability.

    Method
    

    Patients with EGFR TKI-naïve EGFRm+ NSCLC received 40 mg/day afatinib until lack of clinical benefit (determined by investigator). The primary endpoint was incidence of serious adverse events (SAEs). Secondary endpoints were number of patients with drug-related AEs, and time to symptomatic progression (TTSP). Further endpoints included progression-free survival (PFS). For biomarker analysis, peripheral blood samples were collected during scheduled visits from patients entering the study at Beijing Cancer Hospital. DNA extracted from samples collected at Visit 3 and baseline was analyzed for EGFR and pre-specified non-EGFR mutations, respectively, using an amplification-refractory mutation system.

    Result
    

    In total, 64 patients were included in the biomarker analysis. Baseline characteristics: Chinese, 100%; female, 70.3%; mean age, 57.4 years; EGFR mutations: L858R, 50%; Del19, 42.2%. All patients experienced ≥1 drug-related AE, most commonly (grouped terms; any grade/≥3): diarrhea (n=63/9, 98.4%/14.1%) and rash or acne (n=52/5, 81.3%/7.8%). SAEs were reported for 15 patients (23.4%), most commonly cerebral infarction (n=3, 4.7%), malignant neoplasm progression, CNS metastases (both n=2, 3.1%). Median TTSP was 13.5 months (95% CI: 10.9, 18.0). At baseline, 19 of 42 patients analyzed (45.2%) had additional non-EGFR mutations; 17 (89.5%) progressed/died. Median PFS was 8.1 months in these patients, versus 12.5 months for patients with EGFR-only mutations (HR, 1.72; 95% CI 0.88, 3.36; p=0.1054). At Visit 3, mutation status had changed from EGFRm+ to EGFR mutation-negative in 33 of 40 patients analyzed (82.5%). Of these, 29 (87.9%) progressed/died; median PFS was 11.0 months versus 5.5 months for patients who remained EGFRm+ (HR, 1.25; 95% CI: 0.47, 3.30; p=0.6556).

    Conclusion
    

    In this analysis, safety data were consistent with the known safety profile of afatinib. Median PFS was twice as long in patients who became EGFR mutation-negative compared with those who remained EGFRm+; however, the difference was not statistically significant. There was no significant difference in PFS for patients with additional non-EGFR versus those with EGFR-only mutations. This exploratory analysis suggests that afatinib has clinical benefit for patients with EGFRm+ NSCLC across all the subgroups assessed.

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