Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC): First report of efficacy and safety from a pivotal randomized phase (ph) 2 trial (ALTA).

Kim, Dong-Wan; Tiseo, Marcello; Ahn, Myung‐Ju; Reckamp, Karen L.; Hansen, Karin Holmskov; Huber, Rudolf M.; West, Howard; Groen, Harry J.M.; Hochmair, Maximilian; Leighl, Natasha B.; Gettinger, Scott; Langer, Corey J.; Paz‐Ares, Luis; Smit, Egbert F.; Kim, Edward S.; Reichmann, William M.; Kerstein, David; Haluska, Frank G.; Camidge, D. Ross

doi:10.1200/jco.2016.34.15_suppl.9007

Cited by 35 publications

(36 citation statements)

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“…[94][95][96][97][98][99][100][101][102][103][104] Ceritinib is an orally active TKI of ALK, which also inhibits the insulin-like growth factor 1 (IGF-1) receptor but not MET. An expanded phase I trial showed that ceritinib was very active in 122 patients with locally advanced or metastatic NSCLC who have ALK gene rearrangements.…”

Section: Alk Gene Rearrangementsmentioning

confidence: 99%

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Ettinger¹,

Wood²,

Aisner³

et al. 2017

J Natl Compr Canc Netw

1,110

1,005

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Section: Alk Gene Rearrangementsmentioning

confidence: 99%

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Ettinger¹,

Wood²,

Aisner³

et al. 2017

J Natl Compr Canc Netw

1,110

1,005

View full text Add to dashboard Cite

show abstract

“…Updated data presented at the 2016 World Conference on Lung Cancer (WCLC) showed a mPFS of 13.4 months in crizotinib-refractory patients, which is longer than for ceritinib and alectinib in this setting [34]. An AE unique to brigatinib is early pulmonary events, including cough, dyspnea, pneumonia/pneumonitis, and hypoxia, which occurred in 6–8% of patients [33, 35] with onset typically within 7 days after initiation of brigatinib therapy. The phase II ALTA trial therefore looked at two different dosing schedules at either 90 mg daily (group A) or 90 mg daily with escalation to 180 mg daily after 7 days (group B).…”

Section: Therapeutic Optionsmentioning

confidence: 99%

The Current Landscape of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer: Emerging Treatment Paradigms and Future Directions

Qin

Gadgeel

2017

Targ Oncol

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Tumorigenic rearrangements in anaplastic lymphoma kinase (ALK) account for 3–7% of all non-small cell lung cancers (NSCLC). Treatment with targeted tyrosine kinase inhibitors (TKIs) has shown impressive clinical responses. Crizotinib was the first agent approved for front-line therapy of ALK-rearranged NSCLC after it demonstrated superiority to chemotherapy in response rate, duration of response, and progression-free survival. However, eventually all patients progress on crizotinib therapy, with the central nervous system (CNS) being the most common site, which served as the impetus for the development of more potent next-generation ALK inhibitors. Currently, ceritinib, alectinib, and brigatinib are all approved for second-line therapy after progression on or intolerance to crizotinib. Investigations into whether the initiation of a second-generation ALK inhibitor as first-line therapy is the superior treatment paradigm has resulted in the approval of ceritinib as initial therapy. Alectinib has also shown impressive results as front-line therapy, as recently reported in two large randomized studies that compared it to crizotinib. There is a significant need to better understand the drivers of and mechanisms underlying resistance to ALK inhibitors. While specific mutations have been identified, there is currently only limited evidence that the identification of specific mutations should impact selection of the next ALK inhibitor. The best treatment option for patients who become TKI refractory is also unclear, though there is some evidence to suggests that these patients are not responsive to checkpoint inhibitors and may respond better to chemotherapy. Combination therapy with other classes of agents may help to overcome resistance mechanisms and should be investigated further.

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“…Two other ALK inhibitors (brigatinib and lorlatinib) showed promising activity in crizotinib pre-treated ALK-rearranged patients and one of them, brigatinib, received a breakthrough therapy designation by the FDA in October 2014 for crizotinib-resistant ALK-rearranged NSCLC 44,45 . Of note, both agents are highly active even in patients with CNS disease.…”

Section: Alk-rearranged Nsclcmentioning

confidence: 99%

Lung Cancer Management: where are we in 2017?

Scagliotti¹,

Bironzo²,

Rosell³

2017

BRN

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Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC): First report of efficacy and safety from a pivotal randomized phase (ph) 2 trial (ALTA).

Cited by 35 publications

References 0 publications

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

The Current Landscape of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer: Emerging Treatment Paradigms and Future Directions

Lung Cancer Management: where are we in 2017?

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