Abstract 1350P
Background
The next-generation ALK inhibitor brigatinib is approved for use post-crizotinib in ALK+ mNSCLC based on phase II trial (ALTA) data. The phase III ALTA-1L trial showed that brigatinib improves progression-free survival (PFS) vs crizotinib (HR=0.49, 95% CI 0.35–68; P<0.0001 based on blinded independent review) in ALK TKI-naïve patients (pts). We report final data from the UVEA-Brig study of brigatinib use in clinical practice.
Methods
UVEA-Brig is a retrospective chart review of pts who started brigatinib between 06/16 and 12/17 in Italy, Norway, Spain and the UK in an Expanded Access Program. Adults with ALK+ mNSCLC, including those with brain lesions, who were resistant to or intolerant of ≥1 prior ALK TKI and with ECOG performance status ≤3 were eligible. Pts received brigatinib 180 mg once daily with a 7-day lead-in at 90 mg. The primary objective was to describe baseline characteristics, prior therapy, clinical outcomes and safety with brigatinib.
Results
Data for 104 pts (male: 43.3%; median age: 53 [29–80] years; never smoker: 50.0%; adenocarcinoma: 95.2%; metastatic at diagnosis: 86.5%; brain lesions at brigatinib initiation: 62.5%) were analysed. Pts had received a median of 2 (1–6) lines of systemic therapy prior to brigatinib (37.5% had received ≥3) and a median of 1 (1–5) prior ALK TKI (crizotinib 83.7%; ceritinib 50.0%; alectinib 6.7%; lorlatinib 4.8%). At the time of analysis, 77 pts had discontinued brigatinib (progression: 71.4%; adverse event: 5.2% [pneumonitis (2), asthenia/fatigue, amylase and creatine kinase increase]; other: 23.4%). 32 pts continued brigatinib beyond progression. Pt outcomes with brigatinib are shown in the table. 53 pts received subsequent systemic therapy; 42 had an ALK inhibitor, most commonly lorlatinib (n=36). Table: 1350P
| Line of brigatinib initiation | Median OS, months (95% CI) | Median PFS, months (95% CI) | Median duration of response, months (95% CI) |
| Any (n=104) | 23.3 (16.0–not reached [NR]) | 11.3 (8.6–12.9) | NR (19.9–NR) (n=37) |
| Second (n=23) | NR (16.5–NR) | 15.3 (6.4–25.1) | NR (6.8–NR) (n=9) |
| Third (n=42) | 23.3 (15.0–NR) | 11.4 (8.3–15.5) | 19.9 (13.1–NR) (n=17) |
| Fourth (n=22) | 12.1 (5.6–21.3) | 11.2 (5.6–14.3) | 17.4 (4.1–NR) (n=3) |
| Fifth or later (n=17) | NR (6.0–NR) | 8.3 (4.4–12.1) | NR (6.1–NR) (n=8) |
Conclusions
These real-world data indicate the substantial activity and tolerability of brigatinib in pts with ALK+ mNSCLC who were more heavily pretreated than pts included in clinical trials.
Clinical trial identification
Editorial acknowledgement
Medical writing assistance was provided by Andy Noble of Bioscript Group, Macclesfield, UK.
Legal entity responsible for the study
Takeda Pharmaceuticals International AG.
Funding
Takeda Pharmaceuticals International AG.
Disclosure
S. Popat: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda Pharmaceuticals International; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self): Chugai Pharma; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: AbbVie; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Paredox Therapeutics; Advisory/Consultancy: Incyte; Research grant/Funding (institution): Epizyme; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Lilly. O.T. Brustugun: Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Takeda Pharmaceuticals International; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer. J. Cadranel: Advisory/Consultancy: Takeda Pharmaceuticals International; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche. E. Felip: Honoraria (self), Research grant/Funding (institution): Takeda Pharmaceuticals International. M.C. Garassino: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution), Local PI, enrolment in clinical trials: Novartis; Advisory/Consultancy, Local PI, enrolment in clinical trials: Pfizer; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Inivata; Advisory/Consultancy: Sanofi Aventis; Speaker Bureau/Expert testimony, Local PI, enrolment in clinical trials: Otsuka Pharma; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Incyte; Advisory/Consultancy, Speaker Bureau/Expert testimony, Local PI, enrolment in clinical trials: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Local PI, enrolment in clinical trials: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Local PI, enrolment in clincial trials: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Local PI, enrolment in clinical trials: Celgene; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Local PI, enrolment in clinical trials: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Local PI, enrolment in clinical trials: AstraZeneca; Advisory/Consultancy, Local PI, enrolment in clinical trials: Tiziana Sciences; Advisory/Consultancy, Local PI, enrolment in clinical trials: Clovis; Advisory/Consultancy, Local PI, enrolment in clinical trials: Bayer; Advisory/Consultancy, Local PI, enrolment in clinical trials: Merck Serono; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): AstraZeneca AB - United Therapeutics Corporation; Advisory/Consultancy, Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): GSK; Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicine. F. Griesinger: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: ASTRA; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boehringer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Takeda; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Ariad; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: AbbVie; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Siemens; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer. Å. Helland: Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda Pharmaceuticals International; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: PierreFabre; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie. M.J. Hochmair: Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda Pharmaceuticals International; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer. M. Pérol: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Takeda Pharmaceuticals International; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Speaker Bureau/Expert testimony: Amgen; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Chugai; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Speaker Bureau/Expert testimony: Illumina. N. Bent-Ennakhil: Full/Part-time employment: Takeda Pharmaceuticals International. C. Kruhl: Full/Part-time employment: Takeda Pharmaceuticals International. S. Novello: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda Pharmaceuticals International; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AZ; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BI; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly.