Abstract
BackgroundThe next-generation ALK inhibitor brigatinib is approved for use in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC and in patients previously treated with crizotinib. A phase II trial showed that brigatinib is active in patients with ALK-positive metastatic NSCLC (mNSCLC) who had progressed on prior crizotinib (response rate 56 %, median PFS 16.7 months, median OS 34.1 months). We report final data from the UVEA-Brig study of brigatinib in ALK inhibitor-pretreated ALK-positive mNSCLC in clinical practice. MethodsUVEA-Brig was a retrospective chart review of patients treated with brigatinib in Italy, Norway, Spain and the UK in an expanded access program. Adults with ALK-positive mNSCLC, including those with brain lesions, resistant to or intolerant of ≥1 prior ALK inhibitor and ECOG performance status ≤3 were eligible. Patients received brigatinib 180 mg once daily with a 7-day lead-in at 90 mg. The objectives were to describe patient characteristics, clinical disease presentation, treatment regimens used and clinical outcomes. ResultsData for 104 patients (male: 43 %; median age: 53 [29–80] years; ECOG performance status 0/1/2/3: 41/41/10/5 %; brain/CNS metastases: 63 %) were analyzed. Patients had received a median of 2 (1–6) lines of systemic therapy prior to brigatinib (37.5 % received ≥3) and a median of 1 (1–5) lines of prior ALK inhibitor-containing therapy (crizotinib 83.6 %; ceritinib 50.0 %; alectinib 6.7 %; lorlatinib 4.8 %). At the time of analysis, 77 patients had discontinued brigatinib. Overall, the response rate was 39.8 %, median PFS was 11.3 (95 % CI:8.6–12.9) months and median OS was 23.3 (95 % CI: 16.0–NR) months. Four patients discontinued brigatinib treatment due to adverse events. 53 patients received systemic therapy after brigatinib, 42 with an ALK inhibitor (lorlatinib, n = 34). ConclusionsThese real-world data indicate the activity and tolerability of brigatinib in patients with ALK-positive mNSCLC who were more heavily pretreated than patients included in clinical trials.
Highlights
Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of diagnosed lung cancers [1]
The UVEA-Brig study, a retrospective analysis of patients with Anaplastic lymphoma kinase (ALK) + metastatic NSCLC who were treated with brigatinib in an expanded access program (EAP) in four European countries, has provided real-world data indicating that brig atinib has substantial activity and is generally well tolerated when used in daily clinical practice to treat patients with ALK + metastatic NSCLC who had been considerably more heavily pretreated than those enrolled into clinical trials [14,27,28,31]; in addition, patients with poorer Eastern Cooperative Oncology Group (ECOG)
A further strength is that this study provides insight into brigatinib treatment in both patients who received brigatinib second line as well as in patients with more heavily pre treated, very advanced NSCLC, some of whom had exhausted available treatment options and were unable to participate in clinical trials
Summary
Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of diagnosed lung cancers [1]. Patients had received a median of 2 (1–6) lines of Abbreviations: AE, adverse event; ALK, anaplastic lymphoma kinase; BIRC, blinded independent review committee; CI, confidence interval; CNS, central nervous system; CR, complete response; CT, chemotherapy; DoR, duration of response; DoT, duration of treatment; EAP, expanded access program; ECOG, Eastern Coop erative Oncology Group; EMA, European Medicines Agency; EOPE, early-onset pulmonary event; GPP, Good Pharmacoepidemiology Practice; IO, immunotherapy; ISPE, International Society for Pharmacoepidemiology; mNSCLC, metastatic non-small cell lung cancer; NR, not reached; NSCLC, non-small cell lung cancer; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; ROS1, c-ros oncogene 1; SD, stable disease; TKI, tyrosine kinase in hibitor; TTD, time to discontinuation; UVEA-Brig, Use Via Expanded Access to Brigatinib
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