Start Your Search
Targeted therapies and management of brain metastasis (ID 40)
- Event: ELCC 2017
- Type: Proffered Paper session
- Presentations: 1
87O - Brigatinib in ALK+ NSCLC pts with intracranial CNS metastases in 2 clinical trials (ID 241)
16:45 - 18:15 | Author(s): L.A. Bazhenova
The investigational next-generation anaplastic lymphoma kinase (ALK) inhibitor brigatinib is being evaluated in patients (pts) with ALK-positive non–small cell lung cancer (ALK+ NSCLC) in a phase 1/2 trial (Ph1/2) and a pivotal phase 2 trial (ALTA); most of these pts had intracranial central nervous system (CNS) metastases at baseline.
In Ph1/2 (NCT01449461), pts with advanced malignancies, including ALK+ NSCLC, received brigatinib (30–300 mg/d). In ALTA (NCT02094573), crizotinib-resistant pts with advanced ALK+ NSCLC received brigatinib at 90 mg qd in arm A or 180 mg qd with a 7-day lead-in at 90 mg in arm B. ALK+ NSCLC pts with baseline brain metastases were analyzed. CNS efficacy in both trials and safety in ALTA are shown.
In Ph1/2 and ALTA, 50/79 (63%) and 154/222 (69%) ALK+ NSCLC pts had baseline brain metastases based on independent review committee (IRC) and investigator assessment, respectively. Most pts had received chemotherapy (Table). In Ph1/2, 25/50 (50%) pts were receiving brigatinib as of 16 November 2015; in ALTA, 101/154 (66%) pts were receiving brigatinib as of 29 February 2016. In pts with measurable brain lesions, confirmed intracranial objective response rate was 53% in Ph1/2 and 42%/67% in ALTA A/B (Table). In pts with only nonmeasurable brain lesions, 35% (11/31) in Ph1/2 and 7% (4/54)/18% (10/55) in ALTA A/B had confirmed complete resolution of brain lesions. Further data are shown in the table. The most common treatment-emergent adverse events (TEAEs) in the 151 treated ALTA pts with baseline brain metastases were nausea (A/B, 32%/43%), headache (30%/30%), diarrhea (18%/36%), cough (21%/30%), and vomiting (25%/26%); the most common grade ≥3 TEAEs were increased blood creatine phosphokinase (1%/11%), hypertension (4%/7%), increased lipase (3%/3%), and pneumonia (1%/4%).
Brigatinib yielded substantial clinical activity in ALK+ NSCLC pts with brain metastases in 2 trials.rnTable: 87OBaseline characteristics and IRC-assessed intracranial efficacy of brigatinib in ALK+ NSCLC Pts with brain metastases at baselinern
rnrniDCR = intracranial disease control rate, iORR = intracranial objective response rate (confirmed), iPFS = intracranial progression-free survivalrnaLast scan date: 8 October 2015 in Ph1/2; 14 April 2016 in ALTArnbNo prior brain radiotherapy in Ph1/2; active (untreated or treated and progressed) brain lesions in ALTArn
rnrn rn Ph1/2 n = 50rn ALTA Arm A n = 80rn ALTA Arm B n = 74rn rnrn Median age, yearsrn 53rn 49rn 55rn rnrn Received prior chemotherapy, %rn 76rn 74rn 76rn rnrn Crizotinib-naive, %rn 8rn 0rn 0rn rnrn Pts evaluable for intracranial efficacy by IRC, n[a]rn 46rn 80rn 73rn rnrn Median iPFS, monthsrn 14.6rn 15.6rn 12.8rn rnrn Pts with measurable brain lesions, nrn 15rn 26rn 18rn rnrn iORR, n (%)rn 8 (53)rn 11 (42)rn 12 (67)rn rnrn iDCR, n (%)rn 13 (87)rn 22 (85)rn 15 (83)rn rnrn No rad/active[b] subset, nrn 9rn 19rn 15rn rnrn iORR, n (%)rn 6 (67)rn 8 (42)rn 11 (73)rn rnrnrn iDCR, n (%)rn 8 (89)rn 16 (84)rn 14 (93)rn
Clinical trial identification:
NCT01449461 and NCT02094573
Legal entity responsible for the study:
ARIAD Pharmaceuticals, Inc.
ARIAD Pharmaceuticals, Inc.
M. Tiseo: Consulting or advisory role (AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Novartis, Otsuka, Pierre Fabre), research funding (ARIAD). R.M. Huber: Honoraria (ARIAD, AstraZeneca, BMS, Boehringer Ingelheim, Pfizer, Roche), consulting or advisory role (BMS, Boehringer Ingelheim, Celgene, Clovis Oncology, Eli Lilly, Novartis, Roche), research funding (Pierre Fabre). L.A. Bazhenova: Stock and other ownership interests (Epic Sciences), honoraria (Novartis), consulting or advisory role (AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Clovis Oncology, Genoptix, Heat Biologics, Pfizer, Roche/Genentech, Seattle Genetics, Trovagene), speakers bureau (AstraZeneca, Novartis, Pfizer, Roche/Genentech), research funding (AbbVie, ARIAD, Astellas, Astex, AstraZeneca/MedImmune, Boehringer Ingelheim, Chugai, Clovis Oncology, Eisai, Eli Lilly, Heat Biologics, Johnson & Johnson, Merck, Mirati, NanoCarrier, Novartis, Pfizer, Roche/Genentech). S-H.I. Ou: Advisory board (ARIAD). W. Reichmann, J. Haney, D. Kerstein: Employment, stock and other ownership interests (ARIAD). D.R. Camidge: Honoraria (ARIAD), research funding (ARIAD). S.N. Gettinger: Consulting or advisory role (ARIAD, BMS, Janssen), research funding (ARIAD, AstraZeneca/MedImmune, BMS, Boehringer Ingelheim, Incyte, Pfizer, Roche/Genentech). All other authors have declared no conflicts of interest.
Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.