Author of

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  Proffered Paper session I (ID 57)

  • Event: ELCC 2019
  • Type: Proffered Paper session
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 4/10/2019, 16:30 - 18:15, Room C

  • 28966

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    83O - Impact of subsequent post-discontinuation immunotherapy on overall survival in patients with unresectable, stage III NSCLC from PACIFIC (ID 303)

    16:30 - 18:15  |  Author(s): Pralay Mukhopadhyay
    • Abstract
    • Presentation
    • Slides

    Background
    

    In cancer trials, pts often receive subsequent lines of anticancer Tx following progression, which, in standard ITT analyses, can lead to bias and underestimation of OS Tx effect. In the phase 3 PACIFIC trial of durvalumab vs. placebo in Stage III NSCLC pts without progression after CRT, both primary endpoints PFS and OS were met, significantly improved with durvalumab. However, after discontinuation, many pts received further anticancer Tx (41% and 54% in the durvalumab and placebo groups), including immunotherapies (IMTs), which may have influenced OS. Using the Rank Preserving Structural Failure Time (RPSFT) model, we quantified the specific impact of subsequent IMT on OS in PACIFIC.

    a9ded1e5ce5d75814730bb4caaf49419 Methods
    

    RPSFT modeling is commonly used for analysis of trials with crossover. By assuming a similar effect for Tx in different sequences, RPSFT is capable to pinpoint the most likely effect size based on observed data. Here, we adapted RPSFT to isolate the likely effect of subsequent IMT by assuming similar mortality risk reduction for nivolumab, pembrolizumab, and durvalumab. RPSFT analyses were applied to quantify health outcomes for two hypothetical scenarios: (1) no subsequent IMT was received by pts in either arm, and (2) among placebo pts who received subsequent Tx (54%), all received IMT as first subsequent Tx, and durvalumab pts received no subsequent IMT, to test if delaying IMT was detrimental.

    20c51b5f4e9aeb5334c90ff072e6f928 Results
    

    Among pts randomized to durvalumab and placebo, 8% (38/476) and 22% (53/237), respectively, received subsequent IMT. Within the ITT population, the HR for OS with durvalumab vs. placebo was 0.68 (95% CI, 0.53–0.87), with respective median OS not reached (NR) and 28.7 months. For scenario 1, there was minimal change in OS, with an estimated HR of 0.67 (95% CI, 0.52–0.86) and identical median OS estimates. For scenario 2, the estimated HR was 0.79 (95% CI: 0.62–1.00), with median OS NR and 32.2 months, respectively.

    fd69c5cf902969e6fb71d043085ddee6 Conclusions
    

    After removing the effects of subsequent IMT, the OS benefit with durvalumab was still evident compared with the ITT analysis. In addition, early Tx with durvalumab after CRT appeared to be associated with improved OS compared with starting IMT after progression.

    b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification
    

    NCT02125461.

    7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement
    

    Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Hashem Dbouk, PhD, of Cirrus Communications, an Ashfield company, and was funded by AstraZeneca.

    934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study
    

    AstraZeneca.

    213f68309caaa4ccc14d5f99789640ad Funding
    

    AstraZeneca.

    682889d0a1d3b50267a69346a750433d Disclosure
    

    M. Ouwens, Y. Zhang, P. Mukhopadhyay: Employment, stock options: AstraZeneca, outside the conduct of the study. A. Darilay, J. Ryan: Employment, stock: AstraZeneca, outside the conduct of the study. H. Mann: Employment: AstraZeneca, outside conduct of the study. P.A. Dennis: Employment, stocks: AstraZeneca, outside the submitted work.

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