Author of

• 28971

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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

  • 29058

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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  |  Author(s): Keith Wilner
    • Abstract

    Background
    

    Concomitant use of PPIs has been shown to decrease DACO AUC_last and C_max 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 (C_trough) 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 C_trough (C_GM) for each patient per dose level was calculated to represent the patient’s C_trough. 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 C_GM, 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
    

    Pfizer.

    213f68309caaa4ccc14d5f99789640ad Funding
    

    Pfizer.

    682889d0a1d3b50267a69346a750433d Disclosure
    

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

    cffcb1a185b2d7d5c44e9dc785b6bb25

• 29178

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  Proffered Paper session III (ID 64)

  • Event: ELCC 2019
  • Type: Proffered Paper session
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 4/12/2019, 08:30 - 10:00, Room A

  • 29179

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    107O - Crizotinib in advanced ROS1-rearranged non-small cell lung cancer (NSCLC): Overall survival (OS) and updated safety from PROFILE 1001 (ID 197)

    08:30 - 10:00  |  Author(s): Keith Wilner
    • Abstract
    • Presentation
    • Slides

    Background
    

    In the ongoing phase 1 PROFILE 1001 study (NCT00585195), crizotinib provided a meaningful clinical benefit for patients (pts) with advanced ROS1-rearranged NSCLC, as evidenced by a high objective response rate (72%) and rapid, substantial and durable responses (median duration of response, 18 months [mo]); in addition, crizotinib was well-tolerated (Shaw, N Engl J Med, 2014). Here, we present OS results and updated safety (additional follow-up >3 years) in these pts.

    a9ded1e5ce5d75814730bb4caaf49419 Methods
    

    Pts with histologically confirmed NSCLC containing ROS1 rearrangements were enrolled and treated with oral crizotinib 250 mg twice daily (BID). ROS1 status was assessed by fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction.

    20c51b5f4e9aeb5334c90ff072e6f928 Results
    

    Between October 2010 and June 2018, 53 pts with ROS1-rearranged NSCLC were treated with crizotinib; median duration of treatment was 22 mo (95% confidence interval [CI]: 15, 36). At the time of data cutoff (June 30, 2018), 12 pts (22.6%) remained on treatment. A total of 26 deaths (49.1%) occurred over a median follow-up period of 63 mo. Median OS was 51 mo (95% CI: 29, not reached) and the probabilities of survival at 12, 24 and 48 mo were 78.8%, 67.0% and 50.7%, respectively. With a median treatment duration nearly 8 mo longer than that for the primary endpoint analysis and 30.2% of patients on treatment for more than 4 years, no new safety signals were noted. The most common grade 3 treatment-related adverse events (TRAEs; in ≥ 5% of pts) were hypophosphatemia (15.1%) and neutropenia (9.4%); no grade 4 TRAEs or treatment-related deaths were reported. With longer follow-up, there were no permanent discontinuations associated with TRAEs.

    fd69c5cf902969e6fb71d043085ddee6 Conclusions
    

    The results of the OS analysis and updated safety information from PROFILE 1001 continue to support the favorable benefit/risk profile of crizotinib 250 mg BID for the treatment of patients with advanced ROS1-positive NSCLC.

    b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification
    

    NCT00585195.

    7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement
    

    Editorial assistance was provided by Vasupradha Vethantham, PhD, of inScience Communications, Springer Healthcare (New York, NY, USA), with funding from Pfizer, Inc.

    934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study
    

    Pfizer, Inc.

    213f68309caaa4ccc14d5f99789640ad Funding
    

    Pfizer, Inc.

    682889d0a1d3b50267a69346a750433d Disclosure
    

    A. Shaw: Fees for consulting/advisory board roles: ARIAD/Takeda, Blueprint Medicines, Daiichi Sankyo, EMD Serono, Foundation Medicine Genentech, Ignyta, KSQ Therapeutics, Loxo, Novartis, Pfizer, Roche, Taiho; Honoraria: Novartis, Pfizer, Roche; Research funding to institution: Daiichi Sankyo, Ignyta, Novartis, Pfizer, Roche/Genentech, TP Therapeutics. Y-J. Bang: Advisory boards: Astellas, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Daiich-Sankyo, Eli Lilly, GreenCross, Genentech/Roche, Hanmi, Novartis,  Merck Serano,  MSD, Samyang Biopharm, Taiho; Research funding to institution: Astellas, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Boeringer Ingelheim, Boston Biomedical, CKD Pharma, Curis, Daiichi Sankyo, Eli Lilly, FivePrime, Glaxo Smith-Kline, Genentech/Roche, Green Cross, MacroGenics, Merck Serano, MSD, Novartis, Pfizer, Ono, Takeda, Taiho. D.R. Camidge: Advisory boards: AbbVie, ARIAD, Array, Celgene, Clovis, Eli Lilly, G1 Therapeutics (DSMB), Genoptix, Ignyta, Mersana Therapeutics, Novartis, Orion, Roche/Genentech, Takeda; Research for investigator-initiated trials: ARIAD, Takeda. G.J. Riely: Funding to institution: Pfizer for the conduct of this research; Research support to institution: Novartis, Roche, Takeda. Compensated consultant: Genentech/Roche. G.I. Shapiro: Research funding to the Dana-Farber Cancer Institute: Pfizer for the conduct of the study; Advisory boards: Eli Lilly, G1 Therapeutics, Merck/EMD Serono, Roche, Pfizer, Vertex Pharmaceuticals. T. Usari, S.C. Wang, K. Wilner: Employee, holds stock: Pfizer. J.W. Clark: Institutional research funding: Pfizer. S-H.I. Ou: Fees for consulting/Advisory board: Pfizer; Research funding to institution: Eli Lilly, Merck/EMD Serono, Pfizer. All other authors have declared no conflicts of interest.

    cffcb1a185b2d7d5c44e9dc785b6bb25

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