1120 - Brigatinib in ALK TKI-pretreated ALK+ metastatic non-small cell lung cancer (mNSCLC): the Use Via Expanded Access to Brigatinib (UVEA-Brig) study

Background

Brigatinib is a next-generation ALK inhibitor with activity against a broad range of ALK mutations and ROS1 rearrangements. It is approved for use post-crizotinib in ALK+ mNSCLC based on phase II trial (ALTA) data, and significantly improved progression-free survival (PFS) vs crizotinib (HR = 0.49) in ALK TKI-naïve patients (pts) in the phase III ALTA-1L trial. UVEA-Brig captures detailed information about brigatinib therapy in a real-world situation.

Methods

UVEA-Brig is a retrospective analysis of data from pts who started brigatinib between 06/16 and 12/17 in Italy, Norway, Spain and the UK in an expanded access program (EAP). Due to legislation in Italy, only data for deceased pts and pts who had been followed up for 18 months could be used. Adults with mNSCLC, including those with brain lesions, who are resistant to or intolerant of at least one prior ALK inhibitor and have ECOG performance status ≤3 are eligible. The primary objective is to describe baseline characteristics, prior therapy, clinical outcomes and safety with brigatinib.

Results

Data for 50 pts are available (male: 40%; never smoker: 54%; adenocarcinoma: 94%: stage IV at diagnosis: 92%; median age: 51 [31–78] years; brain lesions at study entry: 60% [46% irradiated]). Median follow-up 6 (range 0–24) months. Pts had received a median of 2 (range 1–6) lines of prior systemic therapy (≥3 lines: 34%), with a median of 1 (1–5) prior ALK TKI (crizotinib 84%; ceritinib 46%; alectinib 10%; lorlatinib 8%). 36 pts have discontinued brigatinib (progression: 25; adverse events: 3 [pneumonitis, amylase and creatine kinase increase, and asthenia/fatigue]). 43 pts were evaluable for best response: complete response: 1 (2.3%); partial response: 14 (32.6%); stable disease: 20 (46.5%) (response rate: 34.9%; disease control rate: 81.4%). Median response duration was 9.7 (range 0.7–23.4) months. Median PFS was 5.7 (95% CI 6.2–9.9) months; median OS was 10.2 (8.6–12.6) months. 20 pts received subsequent therapies; 17 had an ALK inhibitor, most commonly lorlatinib (n = 10).

Conclusions

These data from daily clinical practice support the activity of brigatinib also in pts with heavily pretreated ALK+ mNSCLC.

Clinical trial identification

Editorial acknowledgement

Andrew Noble, Bioscript Group.

Legal entity responsible for the study

Takeda.

Funding

Takeda.

Disclosure

S. Novello: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda, BMS, Moehringer Ingelheim, Eli Lilly, Celgene, Pfizer, Roche, AstraZeneca, MSD, AbbVie. O.T. Brustugun: Honoraria (institution): Takeda. J. Cadranel: Advisory / Consultancy: Takeda; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Roche. F. Griesinger: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Takeda; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Siemens; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ariad; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AbbVie. M.J. Hochmair: Honoraria (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self): Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Takeda; Advisory / Consultancy: Novartis. M. Pérol: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda. S. Popat: Honoraria (self), Research grant / Funding (institution): BMS, Roche, Takeda, Pfizer, MSD, EMD Serono, Boehringer Ingelheim; Honoraria (self): Chugai, Novartis, Guardant Health, AbbVie, Medscape, Tesaro, OncLive, AstraZeneca; Research grant / Funding (institution): Bayer, Celgene, Synta, Clovis Oncology, Eli Lilly, Epizyne, Ariad; Research grant / Funding (self): Elsevier. N. Bent-Ennakhil: Full / Part-time employment: Takeda. C. Kruhl: Full / Part-time employment: Takeda. All other authors have declared no conflicts of interest.