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
  • Moderators:
  • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall

  • 32151

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    EP1.14-02 - Comparative Efficacy of First-Line Ceritinib at a Dose of 450mg with Food and Alectinib in Advanced ALK+ NSCLC (ID 1213)

    08:00 - 18:00  |  Author(s): Fei Liang
    • Abstract

    Background
    

    Anaplastic lymphoma kinase (ALK) rearrangement occurs in approximately 3% to 7% of patients with non–small cell lung cancer (NSCLC), and the clinical data have demonstrated the success of therapeutic approaches targeting the ALK protein in this patient population. Ceritinib and alectinib were both second generation of ALK inhibitors that approved as first-treatment for ALK+ NSCLC. Ceritinib is initially approved at the recommended dose of 750 mg/day fasted (ceritinib 750-mg fasted). Ceritinib at a dose of 450 mg with food (ceritinib 450-mg fed) compared to ceritinib 750-mg fasted showed consistent efficacy and less gastrointestinal toxicity in the Ascend 8 trial. Although a previous cross-study indirect study compared the efficacy of ceritinib 750-mg fasted with alectinib, the efficacy of ceritinib 450-mg fed compared with alectinib is unknown.

    Method
    

    Progression-free survival of ceritinib 450-mg fed was indirectly compared with that of alectinib using a Bucher anchor-based indirect comparison approach using ceritinib 750-mg fasted as the common anchor. The comparative efficacy of alectinib vs ceritinib 750-mg fasted was obtained from matching-adjusted indirect comparison(MAIC) and the comparative efficacy of ceritinib 450-mg fed vs ceritinib 750-mg fasted was estimated using reconstructed individual patient-level data from Ascend-8 trial. The corresponding 95% CI of HR for ceritinib 450-mg fed vs alectinib was calculated using the standard errors of the HRs of alectinib vs ceritinib 750-mg fasted and ceritinib 450-mg fed vs ceritinib 750-mg fasted.

    Result
    

    The HR of alectinib vs ceritinib 750-mg fasted in the MAIC was 0.78 (95% CI 0.50-1.23). The estimated HR of ceritinib 450-mg fed vs ceritinib 750-mg fasted was 0.71(95% CI 0.41-1.23). In the anchor-based indirect comparison, HR of ceritinib 450-mg fed vs alectinib was 0.91(0.45-1.85).

    Conclusion
    

    In the cross-study indirect comparison, the efficacy of ceritinib 450-mg fed was comparable with alectinib with numerically lower hazard of progression or death. However, results from indirect comparison can be limited by unobserved or unmeasured confounding. Head-to-head randomized phase III trials are needed to formally compare the efficacy of ceritinib 450-mg fed vs alectinib