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PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)
- Event: WCLC 2018
- Type: Plenary Session
- Track: Advanced NSCLC
- Presentations: 1
- Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
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): Cesare Gridelli
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, %
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.
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