Author of

• 25088

  +

  PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)

  • Event: WCLC 2018
  • Type: Plenary Session
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall

  • 27888

    +

    PL02.03 - Brigatinib vs Crizotinib in Patients With ALK Inhibitor-Naive Advanced ALK+ NSCLC: First Report of a Phase 3 Trial (ALTA-1L) (ID 11155)

    08:30 - 08:40  |  Author(s): Maria Rosario Garcia Campelo
    • Abstract
    • Presentation
    • Slides

    Background
    

    Brigatinib has robust efficacy in crizotinib-resistant ALK+ NSCLC, exhibiting median progression-free survival (mPFS) of 16.7 months. We report results of the first interim analysis from the ALTA-1L study of brigatinib vs crizotinib in ALK TKI-naive, ALK+ NSCLC (NCT02737501).

    This open-label, multicenter study enrolled patients with stage IIIB/IV ALK+ NSCLC based on local ALK testing (FDA approved/other). Eligible patients had ECOG PS 0–2, ≤1 prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor. Asymptomatic CNS metastases were allowed. All patients had systematic CNS imaging. Patients were randomized 1:1 to brigatinib 180 mg QD with 7-day lead-in at 90 mg or crizotinib 250 mg BID. Primary endpoint: blinded independent review committee (BIRC)-assessed PFS (RECIST v1.1). Secondary efficacy endpoints included BIRC-assessed objective response rate (ORR), intracranial ORR (iORR), and intracranial PFS (iPFS). Interim analyses were planned at 50% and 75% of planned PFS events (n=198).

    275 patients were randomized (brigatinib/crizotinib, n=137/138); median age (years) 58/60. 26%/27% received prior chemotherapy for advanced disease, and 29%/30% had baseline brain metastases. At data cut-off (19 February 2018), median follow-up brigatinib/crizotinib: 11.0/9.25 months; with 99 PFS events, brigatinib met the prespecified threshold for statistical superiority vs crizotinib in the primary endpoint, BIRC-assessed PFS (HR 0.49, 95% CI 0.33–0.74, log-rank P=0.0007); brigatinib mPFS was not reached (95% CI NR–NR) vs crizotinib 9.8 months (95% CI 9.0–12.9). Investigator-assessed PFS HR 0.45 (95% CI 0.30–0.68), log-rank P=0.0001. Table shows additional efficacy data. Most common treatment-emergent AEs grade ≥3: brigatinib: increased CPK (16.2%), increased lipase (13.2%), hypertension (9.6%); crizotinib: increased ALT (9.5%), AST (5.8%), and lipase (5.1%). Any grade ILD/pneumonitis: brigatinib, 3.7%; crizotinib, 2.2%. Discontinuations due to AE (brigatinib/crizotinib): 11.8%/8.8%.

    Brigatinib showed a statistically and clinically significant improvement in PFS compared with crizotinib in ALK inhibitor–naive ALK+ NSCLC.

    BIRC-Assessed Endpoint, %	Brigatinib (n=137)	Crizotinib (n=138)	P-Value
    All patients
    ORRa	76 (68–83b)	73 (65–80b)
    Confirmed ORR	71 (62–78b)	60 (51–68b)	0.0678
    With any intracranial CNS metastases
    	(n=43)	(n=47)
    iORRa	79 (64–90b)	23 (12–38b)
    Confirmed iORR	67 (51–81b)	17 (8–31b)	<0.0001
    Median iPFS, months	NR (11–NRb)	6 (4–9b)
    1-year iPFS	67 (47–80b)	21 (6–42b)
    HR	0.27 (0.13–0.54)		<0.0001c
    With measurable intracranial CNS metastases
    	(n=18)	(n=21)
    iORRa	83 (59–96b)	33 (15–57b)
    Confirmed iORR	78 (52–94b)	29 (11–52b)	0.0028
    aResponse, ≥1 assessment; b95% CI; cLog-rank.

    a9ded1e5ce5d75814730bb4caaf49419

    Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

    Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.