First-line ceritinib versus platinum-based chemotherapy in advanced ALK -rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study

Soria, Jean‐Charles; Tan, Daniel S.W.; Chiari, Rita; Wu, Yi‐Long; Paz‐Ares, Luis; Wolf, Juergen; Geater, Sarayut Lucien; Орлов, С. В.; Cortinovis, Diego; Yu, Chong‐Jen; Hochmair, M.J.; Cortot, A.; Tsai, Chun‐Ming; Moro-Sibilot, Denis; Campelo, Rosario García; McCulloch, Tracey; Sen, Paramita; Dugan, Margaret; Pantano, Serafino; Branle, Fabrice; Massacesi, Cristian; Castro, Gilberto de

doi:10.1016/s0140-6736(17)30123-x

Cited by 995 publications

(923 citation statements)

References 20 publications

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“…Prolonged durations of PFS in the TKI-naïve setting have also been reported with the use of ceritinib within the ASCEND-4 trial (NCT01828099, ceritinib versus platinum doublet) (42). Median PFS was 16.6 months (95% CI: 12.6-27.2 months) with ceritinib at a starting dose of 750 mg daily.…”

Section: J-alex and Alex Clinical Trials Confirm Superiority Of Alectmentioning

confidence: 71%

“…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%

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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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Section: J-alex and Alex Clinical Trials Confirm Superiority Of Alectmentioning

confidence: 71%

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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“…The phase III ASCEND-4 trial demonstrated the superiority of ceritinib as first-line therapy for ALK -rearranged NSCLC over platinum–pemetrexed doublet, including improved ORR in the CNS of 72.7% compared to 27.3% [40]. The mPFS as assessed by an independent committee was 16.6 months for ceritinib and 8.1 months for chemotherapy with a HR of 0.55 ( p < 0.00001).…”

Section: Therapeutic Optionsmentioning

confidence: 99%

“…Ceritinib was approved in May 2017 for the front-line treatment of ALK -positive NSCLC but has not been compared head-to-head against crizotinib in the front-line setting. Looking at two different trials, in patients that progressed on crizotinib who then were switched to ceritinib therapy, the combined mPFS was 17.4 months [41] compared to 16.6 months with ceritinib alone [40]. …”

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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“…Both trials met the primary endpoint of improved progression-free survival (PFS) over standard chemotherapy (4,5). Crizotinib 250 mg twice daily compared to cisplatin or carboplatin plus pemetrexed showed a PFS benefit of 10.9 versus 7 months [hazard ratio (HR) 0.45, 95% confidence interval (CI) 0.35-0.60, P<0.0001] and an objective response rate (ORR) of 74% versus 45% with chemotherapy (4).…”

mentioning

confidence: 99%

The J-ALEX trial—is frontline alectinib a new standard of care?

Zweig

Wakelee

2017

J. Thorac. Dis.

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First-line ceritinib versus platinum-based chemotherapy in advanced ALK -rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study

Cited by 995 publications

References 20 publications

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

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

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

The J-ALEX trial—is frontline alectinib a new standard of care?

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