Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial

Shaw, Alice T.; Kim, Tae Min; Crinò, Lucio; Gridelli, Cesare; Kiura, Katsuyuki; Liu, Geoffrey; Novello, Silvia; Bearz, Alessandra; Gautschi, Oliver; Mok, Tony; Nishio, Makoto; Scagliotti, Giorgio Vittorio; Spigel, David R.; Deudon, Stéphanie; Zheng, Cheng; Pantano, Serafino; Urban, Patrick; Massacesi, Cristian; Viraswami-Appanna, Kalyanee; Felip, Enriqueta

doi:10.1016/s1470-2045(17)30339-x

Cited by 495 publications

(408 citation statements)

References 25 publications

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“…The response rate for the ceritinib group was 39.1% compared to 6.9% in the chemotherapy group [24]. While the FDA-approved dose of ceritinib is 750 mg orally daily, 80% of patients in the ASCEND-5 trial required dose adjustment, interruption, or delay, with 61% requiring at least one dose reduction.…”

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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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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“…Nevertheless, the efficacy of ceritinib was established with an ORR of 56% in previously treated patients and 62% in TKI-naïve ALK-rearranged advanced NSCLCs (12). Most importantly, responses were seen in tumors that harbored ALK mutations (such as L1196M, 1151Tins, S1206Y and G1269A), lacked known mechanisms of resistance to crizotinib, and in those patients with brain metastases (12,41,42). Ceritinib received regulatory approval for use in crizotinib-resistant or intolerant patients in 2014.…”

Section: Acquired Resistance To Crizotinib and Development Of Next Gementioning

confidence: 99%

Moving more potent and less toxic options to the frontline in the management of advanced lung cancer

Rangachari

Costa

2017

J. Thorac. Dis.

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“…Ceritinib, an inhibitor of ALK, is now used for patients with cancer progression post crizotinib (16). Encouragingly, it has also been shown to exhibit activity against ROS-1 driven disease, however this requires further clinical validation (17).…”

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confidence: 99%

Emerging resistance pathways in lung cancer: what has ROS-1 taught us?

Alrifai

Förster

Janes

2018

Transl. Lung Cancer Res.

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Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial

Cited by 495 publications

References 25 publications

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

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

Moving more potent and less toxic options to the frontline in the management of advanced lung cancer

Emerging resistance pathways in lung cancer: what has ROS-1 taught us?

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