KEY TAKEAWAYS
- ALTA-2 is a single-arm phase 2 trial evaluating the efficacy of brigatinib in patients with advanced ALK-positive (ALK+) NSCLC who had previously received alectinib or ceritinib.
- Patients received a lead-in dose of brigatinib 90 mg once daily for 7 days and a maintenance dose of 180 mg once daily.
- The (mPFS) was 3.8 months, and patients with ctDNA-detectable baseline ALK fusion had a shorter mPFS of 1.9 months.
- The most common all-grade treatment-related adverse events were increased creatine phosphokinase (32%) and diarrhea (27%), and the mean dose intensity of brigatinib was 85.9%.
Treatment-naive and crizotinib-refractory advanced ALK-positive (ALK+) NSCLC patients can now take brigatinib, a potent next-generation ALK tyrosine kinase inhibitor. Next-generation ALK tyrosine kinase inhibitors were compared to brigatinib. Patients with advanced ALK+ NSCLC who had disease progression on alectinib or ceritinib were given brigatinib 180 mg once daily in this single-arm, phase 2 trial (NCT03535740) (after 7-d 90-mg lead-in). The primary outcome was an independent review committee (IRC) determined the overall response rate (ORR). Circulating tumor DNA (ctDNA) found in the bloodstream was studied.
The median objective response rate (IRC-ORR) was 26.2% (95%[CI]: 18.0-35.8) among 103 patients (data cutoff: September 30, 2020; median follow-up, 10.8 [0.5-17.7] months), the median duration of response was 6.3 months (95% [CI]: 5.6-not reached), and the median progression-free survival (mPFS) was 3.8 months (95% [CI]: 3.5-5.8).
Patients with a ctDNA-detectable ALK fusion at baseline (n = 64) had a median progression-free survival of 1.9 months (95% CI, 1.8-3.7). IRC-ORR was 29.1% (95% [CI]:19.8-39.9), and median progression-free survival (mPFS) was 3.8 months (95% [CI]: 1.9-5.4) among the 86 patients who developed the disease while taking alectinib. EML4-ALK variant 3 was present in 52% (33 of 64) of patients with detectable ALK fusion, and resistance mutations were present in 33.3% (26 of 78) of baseline ctDNA. Diarrhea and elevated creatine phosphokinase were the most common treatment-related adverse events across all grades (32% and 27%, respectively). Brigatinib (180 mg once daily) had an average dose intensity of 85.9%. Patients with ALK+ NSCLC who had previously been treated with either cetuximab or alectinib showed limited response to brigatinib in the ALK in the Lung Cancer Trial of brigAtinib-2. In patients without detectable baseline plasma ALK fusion, brigatinib extended mPFS.
Source: https://pubmed.ncbi.nlm.nih.gov/36096442/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03535740
Ou SI, Nishio M, Ahn MJ, Mok T, Barlesi F, Zhou C, Felip E, de Marinis F, Kim SW, Pérol M, Liu G, Migliorino MR, Kim DW, Novello S, Bearz A, Garrido P, Mazieres J, Morabito A, Lin HM, Yang H, Niu H, Zhang P, Kim ES. Efficacy of Brigatinib in Patients With Advanced ALK-Positive NSCLC Who Progressed on Alectinib or Ceritinib: ALK in Lung Cancer Trial of brigAtinib-2 (ALTA-2). J Thorac Oncol. 2022 Dec;17(12):1404-1414. doi: 10.1016/j.jtho.2022.08.018. Epub 2022 Sep 10. PMID: 36096442.
