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Jerry Li

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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      124P - The effect of proton pump inhibitors (PPI) on dacomitinib (DACO) pharmacokinetics and efficacy in non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutation (ID 322)

      12:30 - 13:00  |  Presenting Author(s): Jerry Li

      • Abstract


      Concomitant use of PPIs has been shown to decrease DACO AUClast and Cmax by approximately 39% and 51% in a healthy volunteer study. ARCHER-1050 (A1050) was a phase 3 study to evaluate DACO as first-line treatment for patients with EGFR-positive advanced NSCLC. A considerable number of patients in A1050 used concomitant PPIs. This analysis evaluates the effects of concomitant PPI use on DACO exposure and progression free survival (PFS) in NSCLC patients treated with DACO using data from A1050.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      Steady-state DACO trough concentrations (Ctrough) were collected on Day 1 of Cycles 2-6 (1 cycle = 28 days). Patients started DACO at 45 mg once daily (QD), but were permitted to dose reduce to 30 then 15 mg QD. The geometric mean of Ctrough (CGM) for each patient per dose level was calculated to represent the patient’s Ctrough. Patients who reported using PPIs at least one dose before and at least one dose after starting DACO treatment were grouped as PPI users, while all other patients were grouped as non-PPI users. The DACO exposure, measured as geometric mean of CGM, was compared between the 2 groups. Statistical analyses were performed using the Kaplan-Meier method and Cox Regression adjusted for several confounding factors. All data processing and analyses were conducted in R, version 3.5.1 (R studio).

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Of the 227 patients who were treated with DACO, baseline characteristics were similar between PPI user (n = 28) and non-PPI user (n = 199) groups, except that PPI user group had a higher percentage of non-Asian patients (61% vs. 20%) than the non-PPI use group. DACO exposure was similar in the 2 groups for each dose level. The median PFS values for PPI users and non-users were 13.1 and 14.9 months, respectively. The Cox Regression Model demonstrated no statistically significant difference in PFS (p > 0.05) between the 2 groups.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      PPI use appeared to have no impact on DACO exposure or on PFS in patients with EGFR-positive advanced NSCLC treated with DACO.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      The data used in this abstract were from the multinational, multicenter, randomized, open-label, phase III ARCHER 1050 study (NCT01774721).

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study


      213f68309caaa4ccc14d5f99789640ad Funding


      682889d0a1d3b50267a69346a750433d Disclosure

      D.J. Nickens, K. Wilner, W. Tan: Employee: Pfizer. All other authors have declared no conflicts of interest.