KEY TAKEAWAYS
- The phase I trial aimed to evaluate the safety and efficacy of combining brigatinib with LCT in TKI-naive ALK-rearranged metastatic NSCLC patients.
- The result demonstrated that brigatinib+LCT was safe for ALK+ NSCLC, achieving better results than brigatinib alone, with benefits linked to smaller post-induction tumors and LCT completion, not starting metastasis count.
Most ALK-TKI responders in advanced non-small cell lung cancer(NSCLC) have lingering tumor (“residual disease”), leading to resistance over time.
For the study, researchers aimed to evaluate the safety and efficacy of combining brigatinib with local consolidative therapy(LCT) in TKI-naive ALK-rearranged metastatic NSCLC patients.
Patients eligible for the study had previously untreated ALK-rearranged advanced NSCLC with oligo- and poly-metastatic disease. They underwent an 8-week treatment regimen involving induction with brigatinib followed by LCT incorporating radiation and/or surgery.
Baseline and post-brigatinib induction tumor images were comprehensively annotated, and disease burden was assessed using overall 3D tumor volume. Individual patient data from a phase 3 trial comparing brigatinib and crizotinib (ALTA-1L, NCT02737501) were retrospectively analyzed for comparison.
About 34 patients, with a median age of 56 (range 33-73), were enrolled. At study entry, (82% n=28) had polymetastatic disease (>3 sites), and 41% (n=14) had brain metastases. LCT modalities included radiation (n=27), surgery (n=3), and surgery + radiation (n=2), 2 patients did not undergo LCT(1 withdrew consent, and 1 had no LCT-amenable disease).
Among 5 surgical patients, procedures included 4 pulmonary lobectomies, 1 sublobar resection, and 1 adrenalectomy. About 2 patients had complete pathological responses. Grade (G) ≥3 LCT-related adverse events (LRAEs) occurred in 4 patients (12%): G4 bronchopulmonary hemorrhage (n=1), G3 pneumonitis (n=1), G3 anemia (n=1), G3 nausea (n=1), G3 vomiting (n=1), and G3 esophagitis.
At the 8-week brigatinib induction end, the disease control rate was 100%, and the objective response rate(ORR) was 79% (95% CI: 62-91, n=27). The result demonstrated favorable progression-free survival (PFS) rates at 1, 2, and 3 years (94%, 80%, and 66%, respectively).
In the ALTA-1L subset, patients with non-progressing NSCLC at 12 weeks had PFS rates of 76%, 56%, and 47% at 1, 2, and 3 years, respectively. Among 12 patients with disease progression in BRIGHTSTAR, 50% showed isolated brain progression.
In univariate Cox modeling, ALK variant and baseline metastatic sites did not predict PFS. Lower disease burden at baseline and post-induction correlated with better PFS (HR=1.006 per 1 cc increase, P=.007). Compared to incomplete, complete LCT to all residual disease sites was significantly beneficial (HR 0.1, 95% CI: 0.02-0.48, P=004).
The study found that brigatinib+LCT was safe for ALK+ NSCLC, achieving better results than brigatinib alone, with benefits linked to smaller post-induction tumors and LCT completion, not starting metastasis count.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/951
Clinical Trials: https://clinicaltrials.gov/study/NCT03707938
https://clinicaltrials.gov/study/NCT02737501
Y. Elamin, S. Gandhi, M. Saad, S. Rehmani, M.B. Antonoff, D.L. Gibbons, X. Le, M. Negrao, V. Lam, M. Altan, J. Tu, C. Gay, L. Byers, T. Cascone, G. Blumenschein, J. Chang, A. Vaporciyan, Z. Liao, S. Swisher, J. Yin, K. Park, P. Zhang, J. Wu, J. Heymach. BRIGHTSTAR: Local Consolidative Therapy with Brigatinib in Tyrosine Kinase Inhibitor-Naïve ALK-Rearranged Metastatic NSCLC.
