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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.