First-Line Crizotinib versus Chemotherapy in <i>ALK</i>-Positive Lung Cancer

Solomon, Benjamin; Mok, Tony; Kim, Dong Wan; Wu, Yi‐Long; Nakagawa, Kazuhiko; Mekhail, Tarek; Felip, Enriqueta; Cappuzzo, Federico; Paolini, Jolanda; Usari, Tiziana; Iyer, Shrividya; Reisman, Arlene; Wilner, Keith D.; Tursi, Jennifer; Blackhall, Fiona

doi:10.1056/nejmoa1408440

Cited by 2,909 publications

(2,356 citation statements)

References 31 publications

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“…Molecular therapy has become a newly emerging regimen over the last decade 4. With lesser toxicity, patients with sensitive molecular alterations could benefit more from an inhibitor therapy than traditional chemotherapy 5, 6, 7, 8, 9, 10.…”

Section: Introductionmentioning

confidence: 99%

Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma

Song

Zhang

2016

Cancer Medicine

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PIK3CA mutation represents a clinical subset of diverse carcinomas. We explored the status of PIK3CA mutation and evaluated its genetic variability, treatment, and prognosis in patients with lung adenocarcinoma. A total of 810 patients with completely resected lung adenocarcinoma were recruited between 2008 and 2013. The status of PIK3CA mutation and other three genes, that is, EGFR mutation, KRAS mutation and ALK fusion were examined by reverse transcription‐polymerase chain reaction (RT‐PCR). Survival curves were plotted with the Kaplan–Meier method and log‐rank for comparison. Cox proportional hazard model was performed for multivariate analysis. Among the 810 patients, 23 cases of PIK3CA mutation were identified with a frequency of 2.8%. There were 14 men and 9 women with a median age of 61 years. Seventeen tumors revealed concurrent gene abnormalities of EGFR mutation (n = 12), KRAS mutation (n = 3), and ALK fusion (n = 2). Seven patients with EGFR & PIK3CA mutations recurred and administrated of EGFR‐TKIs yielded a median progression free‐survival of 6.0 months. Among four eviromous‐treated patients, stable disease was observed in three patients with a median Progression‐free survival (PFS) of 3.5 months. Patients with and without PIK3CA mutation had different overall survivals (32.2 vs. 49.6 months, P = 0.003). Multivariate analysis revealed that PIK3CA mutation was an independent predictor of poor overall survival (HR = 2.37, P = 0.017). The frequency of PIK3CA mutation was around 2.8% in the Chinese patients of lung adenocarcinoma. PIK3CA mutation was associated with reduced PFS of EGFR‐TKIs treatment and shorter overall survival.

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Section: Introductionmentioning

confidence: 99%

Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma

Song

Zhang

2016

Cancer Medicine

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“…However the management of advanced NSCLC has significantly improved during last decade. Innovative oral targeted molecules, such as the anti-EGFR tyrosine kinase inhibitors (TKIs), gefitinib, erlotinib, and afatinib, or the ALK inhibitor, crizotinib, have shown their superiority in terms of response rate, progression-free survival (PFS) and quality of life (QoL) compared with standard chemotherapy for tumours harbouring an activating EGFR mutation or ALK-rearrangement, respectively [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

What can platinum offer yet in the treatment of PS2 NSCLC patients? A systematic review and meta-analysis

Bronte

Rolfo

Passiglia

et al. 2015

Critical Reviews in Oncology/Hematology

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“…There was a significantly higher response rate to crizotinib (65%) versus chemotherapy (20%). In another randomized phase III trial, Solomon et al demonstrated the superiority of crizotinib over standard platinum doublet chemotherapy as first-line therapy for ALK -rearranged NSCLC in PROFILE 1014 [18]. In this study, the median PFS (mPFS) for crizotinib was 10.9 months compared with 7.0 months for chemotherapy (hazard ratio [HR] 0.45, p < 0.001).…”

Section: Therapeutic Optionsmentioning

confidence: 67%

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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First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer

Cited by 2,909 publications

References 31 publications

Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma

Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma

What can platinum offer yet in the treatment of PS2 NSCLC patients? A systematic review and meta-analysis

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

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