Real-World Efficacy and Tolerability of Brigatinib in Patients with Non-Small Cell Lung Cancer with Prior ALK-TKIs in the United States

Abstract

Background Real-world evidence for brigatinib, a next-generation anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) used in ALK-rearranged non-small cell lung cancer, is scarce. This retrospective study evaluated real-world brigatinib utilization in the US post other ALK-TKIs. Materials and Methods Adults with ≥1 brigatinib claim (index date) between 1 April 2017 and 30 September 2020 in the IQVIA longitudinal pharmacy claims database were followed until dose reduction, discontinuation, or end of follow-up. Patients had ≥12 months pre– and ≥1-month post–index observations. Results A total of 413 patients treated with brigatinib were analyzed. Over 80% received ≥1 prior ALK-TKI; alectinib and crizotinib were the most common (58.8% and 51.3% patients, respectively). The median follow-up was 8.4 months. The median time to treatment discontinuation (TTD) for brigatinib was 10.3 months (95% CI, 8.2-15.0), with 45% remaining on therapy at 12 months. The TTD was shortest (~8 months) in patients receiving both crizotinib and alectinib and longest in patients who received alectinib only prior to brigatinib (11.8 months). Adherence was high, with 92.7% of patients having a medication possession ratio of >80%. The mean dose compliance score was 1.0. Most patients reached the brigatinib dose of 180 mg/day (77%); 13.2% of patients had a dose reduction, with 89.3% and 84.6% continuing 180 mg/day therapy at 3 and 6 months, respectively. Conclusions Brigatinib appears to be effective and well-tolerated in the real-world ALK+ NSCLC population in the US, showing benefit in patients after a next-generation ALK-TKI. Notably, dose reduction rates appeared markedly less than those seen in trials when most trial-related dose reductions were for asymptomatic laboratory abnormalities.

Real‐world evidence of brigatinib as second‐line treatment after crizotinib for ALK+ non‐small cell lung cancer using South Korean claims data (K‐AREAL)

“…Most patients in the current study (88.5%) reached the full dose of brigatinib (180 mg/day), and most patients (93.1%) were adherent to treatment. This is consistent with a US real‐world study (in which >80% had received a prior ALK inhibitor), where 77% of patients reached brigatinib 180 mg/day and 92.7% of patients were adherent 13 . The probability of continuing brigatinib therapy at 1 year in the current study (63.2%) was higher than when it was administered as second‐line therapy in the global expanded access programme (49.3%) or as second or later line therapy in the US (45%) and Latin American (59.9%) real‐world studies 13,15,16 .…”

“…13 The probability of continuing brigatinib therapy at 1 year in the current study (63.2%) was higher than when it was administered as second-line therapy in the global expanded access programme (49.3%) or as second or later line therapy in the US (45%) and Latin American (59.9%) real-world studies. 13,15,16 It is possible this could indicate a difference between Asian and non-Asian populations, which would be consistent with the ALTA-1 L clinical trial of brigatinib in ALK inhibitor-naïve patients, which found that PFS was longer in Asian than in non-Asian patients, 37 although no notable difference in PFS was found between these subgroups in the ALTA trial in crizotinibrefractory patients. 10 The current study also assessed TTDR and found a reasonably high probability of continuation on the maximum/peak dose of brigatinib at both 1 and 2 years.…”

“…Available data from the USA, Europe and South America indicate that brigatinib is effective and well tolerated in routine clinical practice. [13][14][15][16][17] However, as well as including data for second-line brigatinib, most current real-world studies include later lines of brigatinib. In addition, there is a lack of real-world data in Asian populations.…”

“…Currently, only limited real‐world evidence for brigatinib has been reported. Available data from the USA, Europe and South America indicate that brigatinib is effective and well tolerated in routine clinical practice 13–17 . However, as well as including data for second‐line brigatinib, most current real‐world studies include later lines of brigatinib.…”

Optimal first-line treatment for metastatic ALK+ non-small cell lung cancer—a narrative review

“…Additionally, brigatinib has demonstrated a unique early pulmonary toxicity as discussed above ( 16 ). This risk can be reduced by commencing brigatinib at a lower dose 90 mg for 7 days before increasing to 180 mg daily if tolerated ( 34 ). If symptomatic pulmonary toxicity is suspected, brigatinib should be withheld pending prompt investigation and management.…”