We believe that this attempt enables clinicians to choose appropriate treatment easier .
According to rapid development of chemotherapy in advanced non-small cell lung cancer ( NSCLC ) , the Japan Lung Cancer Society has been up date d its own guideline annually since 2010 .
Recently , we have had various types of chemotherapeutic drugs like kinase inhibitors or immune-checkpoint inhibitors .
Thus , the guideline proposes to categorize patients into three entities : ( 1 ) driver oncogene-positive , ( 2 ) PD-L1 ≥ 50 % , and ( 3 ) others .
Here , we report an English version of the Japan Lung Cancer Society Guidelines 2018 for NSCLC , stages IV
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.
BACKGROUND Ceritinib is a next-generation anaplastic lymphoma kinase ( ALK ) inhibitor , which has shown robust anti-tumour efficacy , along with intracranial activity , in patients with ALK-rearranged non-small-cell lung cancer . In phase 1 and 2 studies , ceritinib has been shown to be highly active in both ALK inhibitor-naive and ALK inhibitor-pretreated patients who had progressed after chemotherapy ( mostly multiple lines ) . In this study , we compared the efficacy and safety of ceritinib versus single-agent chemotherapy in patients with advanced ALK-rearranged non-small-cell lung cancer who had previously progressed following crizotinib and platinum-based doublet chemotherapy . METHODS In this r and omised , controlled , open-label , phase 3 trial , we recruited patients aged at least 18 years with ALK-rearranged stage IIIB or IV non-small-cell lung cancer ( with at least one measurable lesion ) who had received previous chemotherapy ( one or two lines , including a platinum doublet ) and crizotinib and had subsequent disease progression , from 99 centres across 20 countries . Other inclusion criteria were a WHO performance status of 0 - 2 , adequate organ function and laboratory test results , a life expectancy of at least 12 weeks , and having recovered from previous anticancer treatment-related toxicities . We r and omly allocated patients ( 1:1 ; with blocking [ block size of four ] ; stratified by WHO performance status [ 0 vs 1 - 2 ] and presence or absence of brain metastases ) to oral ceritinib 750 mg per day fasted ( in 21 day treatment cycles ) or chemotherapy ( intravenous pemetrexed 500 mg/m2 or docetaxel 75 mg/m2 [ investigator choice ] , every 21 days ) . Patients who discontinued chemotherapy because of progressive disease could cross over to the ceritinib group . The primary endpoint was progression-free survival , assessed by a masked independent review committee using Response Evaluation Criteria in Solid Tumors 1.1 in the intention-to-treat population , assessed every 6 weeks until month 18 and every 9 weeks thereafter . This trial is registered with Clinical Trials.gov , number NCT01828112 , and is ongoing but no longer recruiting patients . FINDINGS Between June 28 , 2013 , and Nov 2 , 2015 , we r and omly allocated 231 patients ; 115 ( 50 % ) to ceritinib and 116 ( 50 % ) to chemotherapy ( 40 [ 34 % ] to pemetrexed , 73 [ 63 % ] to docetaxel , and three [ 3 % ] discontinued before receiving treatment ) . Median follow-up was 16·5 months ( IQR 11·5 - 21·4 ) . Ceritinib showed a significant improvement in median progression-free survival compared with chemotherapy ( 5·4 months [ 95 % CI 4·1 - 6·9 ] for ceritinib vs 1·6 months [ 1·4 - 2·8 ] for chemotherapy ; hazard ratio 0·49 [ 0·36 - 0·67 ] ; p<0·0001 ) . Serious adverse events were reported in 49 ( 43 % ) of 115 patients in the ceritinib group and 36 ( 32 % ) of 113 in the chemotherapy group . Treatment-related serious adverse events were similar between groups ( 13 [ 11 % ] in the ceritinib group vs 12 [ 11 % ] in the chemotherapy group ) . The most frequent grade 3 - 4 adverse events in the ceritinib group were increased alanine aminotransferase concentration ( 24 [ 21 % ] of 115 vs two [ 2 % ] of 113 in the chemotherapy group ) , increased γ glutamyltransferase concentration ( 24 [ 21 % ] vs one [ 1 % ] ) , and increased aspartate aminotransferase concentration ( 16 [ 14 % ] vs one [ 1 % ] in the chemotherapy group ) . Six ( 5 % ) of 115 patients in the ceritinib group discontinued because of adverse events compared with eight ( 7 % ) of 116 in the chemotherapy group . 15 ( 13 % ) of 115 patients in the ceritinib group and five ( 4 % ) of 113 in the chemotherapy group died during the treatment period ( from the day of the first dose of study treatment to 30 days after the final dose ) . 13 ( 87 % ) of the 15 patients who died in the ceritinib group died because of disease progression and two ( 13 % ) died because of an adverse event ( one [ 7 % ] cerebrovascular accident and one [ 7 % ] respiratory failure ) ; neither of these deaths were considered by the investigator to be treatment related . The five ( 4 % ) deaths in the chemotherapy group were all due to disease progression . INTERPRETATION These findings show that patients derive significant clinical benefit from a more potent ALK inhibitor after failure of crizotinib , and establish ceritinib as a more efficacious treatment option compared with chemotherapy in this patient population . FUNDING Novartis Pharmaceuticals Corporation
We believe that this attempt enables clinicians to choose appropriate treatment easier .
According to rapid development of chemotherapy in advanced non-small cell lung cancer ( NSCLC ) , the Japan Lung Cancer Society has been up date d its own guideline annually since 2010 .
Recently , we have had various types of chemotherapeutic drugs like kinase inhibitors or immune-checkpoint inhibitors .
Thus , the guideline proposes to categorize patients into three entities : ( 1 ) driver oncogene-positive , ( 2 ) PD-L1 ≥ 50 % , and ( 3 ) others .
Here , we report an English version of the Japan Lung Cancer Society Guidelines 2018 for NSCLC , stages IV