Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial
| Autor: | Axelle Nzokirantevye, Sandrine Marreaud, Hans Gelderblom, Sandra Collette, Patrick Schöffski, Silvia Stacchiotti, Agnieszka Wozniak, Piotr Rutkowski, Nicolas Isambert, Lars H. Lindner, Antoine Italiano, Sandra J. Strauss, Jozef Sufliarsky, Raf Sciot, Jean-Yves Blay, Thomas Van Cann, Maria Debiec-Rychter, Michael G Leahy |
|---|---|
| Přispěvatelé: | Department of General Medical Oncology [Leuven], University Hospitals Leuven [Leuven], National Cancer Institute (Bratislava), Leids Universitair Medisch Centrum [Leiden, The Netherlands], Centre Léon Bérard [Lyon], University College London Hospitals (UCLH), Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], The Christie NHS Foundation Trust, University of Manchester [Manchester], Institut Bergonié [Bordeaux], UNICANCER, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium., Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Department of Pathology (University Hospitals Leuven), European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Laboratory of Experimental Oncology (University Hospitals Leuven) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Adult Male medicine.medical_specialty Lung Neoplasms Non-Randomized Controlled Trials as Topic Population Myofibroma Antineoplastic Agents [SDV.CAN]Life Sciences [q-bio]/Cancer 03 medical and health sciences Anaplastic lymphoma kinase 0302 clinical medicine Crizotinib Internal medicine Carcinoma Non-Small-Cell Lung Clinical endpoint Medicine Humans Mesenchymal neoplasm Prospective Studies education Response Evaluation Criteria in Solid Tumors Aged Gene Rearrangement education.field_of_study business.industry Inflammatory myofibroblastic tumour Middle Aged medicine.disease 3. Good health Gene rearrangements Clinical trial Europe 030104 developmental biology Treatment Outcome Drug Resistance Neoplasm 030220 oncology & carcinogenesis Disease Progression Female Liver function business medicine.drug |
| Zdroj: | Lancet Respiratory medicine Lancet Respiratory medicine, Elsevier, 2018, 6 (6), pp.431-441. ⟨10.1016/S2213-2600(18)30116-4⟩ Lancet Respiratory Medicine, 6(6), 431-441 |
| ISSN: | 2213-2600 2213-2619 |
| Popis: | Summary Background An inflammatory myofibroblastic tumour (IMFT) is a rare mesenchymal neoplasm characterised by anaplastic lymphoma kinase (ALK) gene rearrangements. We assessed the activity and safety of crizotinib, a tyrosine kinase inhibitor, targeting ALK in patients with advanced IMFT either with or without ALK alterations. Methods We did a multicentre, biomarker-driven, single-drug, non-randomised, open-label, two-stage phase 2 trial (European Organisation for Research and Treatment of Cancer 90101 CREATE) at 13 study sites (five university hospitals and eight specialty clinics) in eight European countries (Belgium, France, Germany, Italy, Netherlands, Poland, Slovakia, and the UK). Eligible participants were patients aged at least 15 years with a local diagnosis of advanced or metastatic IMFT deemed incurable with surgery, radiotherapy, or systemic therapy; measurable disease; an Eastern Cooperative Oncology Group performance status of 0–2; and adequate haematological, renal, and liver function. Central reference pathology was done for confirmation of the diagnosis, and ALK positivity or negativity was assessed centrally using immunohistochemistry and fluorescence in-situ hybridisation based on archival tumour tissue and defined as ALK immunopositivity or rearrangements in at least 15% of tumour cells. Eligible ALK -positive and ALK -negative patients received oral crizotinib 250 mg twice per day administered on a continuous daily dosing schedule (the duration of each treatment cycle was 21 days) until documented disease progression, unacceptable toxicity, or patient refusal. If at least two of the first 12 eligible and assessable ALK -positive patients achieved a confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, a maximum of 35 patients were to be enrolled. If at least six ALK -positive patients achieved a confirmed response, the trial would be deemed successful. The primary endpoint was the proportion of patients who achieved an objective response (ie, a complete or partial response) as per RECIST 1.1, with response confirmation assessed by the local investigator every other cycle. Activity and safety endpoints were analysed in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT01524926. Findings Between Oct 3, 2012, and April 12, 2017, we recruited and treated 20 eligible participants, 19 of whom were assessable for the primary endpoint. Median follow-up was 863 days (IQR 358–1304). Six of 12 ALK -positive patients (50%, 95% CI 21·1–78·9) and one of seven ALK -negative patients (14%, 0·0–57·9) achieved an objective response. The most common treatment-related adverse events in the 20 participants were nausea (11 [55%]), fatigue (9 [45%]), blurred vision (nine [45%]), vomiting (seven [35%]), and diarrhoea (seven [35%]). Eight serious adverse events occurred in five patients: pneumonia, fever of unknown cause, a heart attack with increased creatinine and possible sepsis, an abdominal abscess with acute renal insufficiency, and a QT prolongation. Interpretation With 50% of participants with ALK -positive tumours achieving an objective response, crizotinib met the prespecified criteria for success in this trial. The results presented here support the rationale for inhibiting ALK in patients with IMFT. Crizotinib could be considered as the standard of care for patients with locally advanced or metastatic ALK -positive IMFT who do not qualify for curative surgery. Funding The European Organisation for Research and Treatment of Cancer and Pfizer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|