Abstract 1120
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.
Resources from the same session
3317 - Circulating tumor DNA (ctDNA) analysis in patients (pts) with non-small cell lung cancer (NSCLC) treated with telisotuzumab vedotin (teliso-v), an antibody-drug conjugate targeting c-Met
Presenter: Rebecca Heist
Session: Poster Display session 1
Resources:
Abstract
3887 - First Real Life Data on Durvalumab after definitive concomitant ChemoRadiotherapy (cCRT) in unresectable Stage (St) III Non-Small Cell Lung Cancer (NSCLC) in France: Analysis of 591 patients (pts) enrolled in the French cohort (c) Temporary Authorization of Use (ATU)
Presenter: Virginie Avrillon
Session: Poster Display session 1
Resources:
Abstract
682 - EGFR Inhibitor Versus Chemotherapy as Adjuvant Treatment for Locally-advanced EGFR-mutant Non-Small Cell Lung Cancer
Presenter: Peng Xie
Session: Poster Display session 1
Resources:
Abstract
2509 - Afatinib in EGFR TKI-naïve patients with EGFR mutation-positive (EGFRm+) NSCLC: interim analysis of a Phase IIIb, multi-national, open-label study
Presenter: Filippo de Marinis
Session: Poster Display session 1
Resources:
Abstract
3300 - First-line ceritinib versus chemotherapy in patients (pts) with advanced ALK rearranged (ALK+) non-small cell lung cancer (NSCLC): ASCEND-4 Asian subgroup analysis
Presenter: Daniel SW Tan
Session: Poster Display session 1
Resources:
Abstract
2653 - A combined analysis of two Phase IIIb studies of afatinib in EGFR TKI-naïve patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC
Presenter: Filippo de Marinis
Session: Poster Display session 1
Resources:
Abstract
3663 - Impact of plasma EGFR mutation fractions on response to first generation tyrosine-kinase inhibitor in treatment of naïve non-small cell lung cancer patients
Presenter: Xiaohong Wang
Session: Poster Display session 1
Resources:
Abstract
5921 - Definition of an afatinib trough concentration threshold in the treatment of NSCLC
Presenter: Stephane Bouchet
Session: Poster Display session 1
Resources:
Abstract
2852 - A Phase Ib Trial of Neoadjuvant Chemoradiotherapy and Durvalumab(MEDI4736) for Potentially Resectable stage III Non-Small Cell Lung Cancer (NSCLC)
Presenter: Beung chul AHN
Session: Poster Display session 1
Resources:
Abstract
3273 - Low expression of Notch1 and combined Notch1/HES1 are associated with adverse survival factor for limited stage small cell lung cancer
Presenter: Jinsoo Lee
Session: Poster Display session 1
Resources:
Abstract