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

Shaw, Alice T.; Kim, Dong Wan; Nakagawa, Kazuhiko; Seto, Takashi; Crinò, Lucio; Ahn, Myung Ju; Pas, Tommaso De; Besse, Benjamin; Solomon, Benjamin; Blackhall, Fiona; Wu, Yi‐Long; Thomas, Michael; O’Byrne, Kenneth J.; Moro-Sibilot, Denis; Camidge, D. Ross; Mok, Tony; Hirsh, Vera; Riely, Gregory J.; Iyer, Shrividya; Tassell, Vanessa; Polli, Anna; Wilner, Keith D.; Jänne, Pasi A.

doi:10.1056/nejmoa1214886

Cited by 3,115 publications

(2,354 citation statements)

References 30 publications

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“…Treatment of ALK fusion‐positive NSCLC with ALK inhibitors results in higher response rates and progression‐free survivals than observed with cytotoxic chemotherapy 4, 5. However, most patients will eventually progress within 8–11 months, either in the brain and/or extra‐cranial sites, as was the case with our patient 4, 5.…”

Section: Discussionsupporting

confidence: 59%

Successful treatment of hepatic oligometastases with stereotactic ablative radiotherapy and radiofrequency ablation in an anaplastic lymphoma kinase fusion‐positive lung cancer patient

Weber

Liu

Sobkin

et al. 2015

J of Medical Radiation Sci

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Local ablative therapy with stereotactic ablative radiotherapy may improve survival in oncogene‐addicted lung cancer patients with extracranial oligometastatic disease treated with targeted therapies. There is limited data on the use of radiofrequency ablation (RFA) in this same setting. We present a case of an anaplastic lymphoma kinase (ALK)‐positive lung cancer patient with hepatic oligometastatic progression who was successfully treated with both stereotactic ablative radiation and RFA while continuing with an ALK inhibitor.

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Section: Discussionsupporting

confidence: 59%

Successful treatment of hepatic oligometastases with stereotactic ablative radiotherapy and radiofrequency ablation in an anaplastic lymphoma kinase fusion‐positive lung cancer patient

Weber

Liu

Sobkin

et al. 2015

J of Medical Radiation Sci

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“…HRQoL was assessed with the European Organisation for Research and Treatment of Cancer quality of life questionnaire C30 (EORTC QLQ-C30) and the lung cancer module QLQ-LC13. The study was open label47 …”

Section: Resultsmentioning

confidence: 99%

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13

Davis

Naci

Gurpinar

et al. 2017

BMJ

487

415

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Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. Design Retrospective cohort study. Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013. Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs. Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years’ follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%). Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.

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“…The drug could induce rapid tumor regression and the majority of patients’ ORR up to 53% 78. However, after long‐time therapy, most of patients develop resistance in <1 year 79…”

Section: The Mechanism Of Brain Metastasismentioning

confidence: 99%

Emerging findings into molecular mechanism of brain metastasis

Chen

2018

Cancer Medicine

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Brain metastasis is an important cause of morbidity and mortality in cancer patients. Hence, the need to develop improved therapies to prevent and treat metastasis to the brain is becoming urgent. Recent studies in this area are bringing about some advanced progress on brain metastasis. It was concluded that the occurrence and poor prognosis of brain metastasis have been mostly attributed to the exclusion of anticancer drugs from the brain by the blood‐brain barrier. And several highly potent new generation targeted drugs with enhanced CNS distribution have been developed constantly. However, the noted “seed and soil” hypothesis also suggests that the outcome of metastasis depends on the relationship between unique tumor cells and the specific organ microenvironment. Moreover, increasing studies in multiple tumor types demonstrated that brain metastasis has great molecular differences between primary tumors and extracranial metastasis to a large extent. Here, the authors summarized the most common malignancies that could lead to brain metastasis—lung cancer, breast cancer and melanoma and their related mutated factors. Only by comprehending a deeper understanding of the molecular mechanisms, more effective brain‐specific therapies will be developed for brain metastasis.

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Crizotinib versus Chemotherapy in AdvancedALK-Positive Lung Cancer

Abstract: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.).

Cited by 3,115 publications

References 30 publications

Successful treatment of hepatic oligometastases with stereotactic ablative radiotherapy and radiofrequency ablation in an anaplastic lymphoma kinase fusion‐positive lung cancer patient

Successful treatment of hepatic oligometastases with stereotactic ablative radiotherapy and radiofrequency ablation in an anaplastic lymphoma kinase fusion‐positive lung cancer patient

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13

Emerging findings into molecular mechanism of brain metastasis

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