PubMed:27573561 JSONTXT

{"project":"luoyt2021_800_3","denotations":[{"id":"T1","span":{"begin":74,"end":84},"obj":"CI"},{"id":"T10","span":{"begin":462,"end":469},"obj":"CI"},{"id":"T11","span":{"begin":2403,"end":2414},"obj":"CI"},{"id":"T12","span":{"begin":2182,"end":2193},"obj":"CI"},{"id":"T13","span":{"begin":1964,"end":1975},"obj":"CI"},{"id":"T14","span":{"begin":1654,"end":1665},"obj":"CI"},{"id":"T15","span":{"begin":1296,"end":1307},"obj":"CI"},{"id":"T16","span":{"begin":284,"end":295},"obj":"CI"},{"id":"T17","span":{"begin":298,"end":305},"obj":"CI"},{"id":"T18","span":{"begin":185,"end":205},"obj":"DP"},{"id":"T2","span":{"begin":86,"end":98},"obj":"CI"},{"id":"T20","span":{"begin":519,"end":523},"obj":"DP"},{"id":"T21","span":{"begin":2507,"end":2511},"obj":"DP"},{"id":"T22","span":{"begin":1333,"end":1340},"obj":"CI"},{"id":"T23","span":{"begin":452,"end":459},"obj":"CI"},{"id":"T24","span":{"begin":149,"end":156},"obj":"CI"},{"id":"T3","span":{"begin":104,"end":118},"obj":"CI"},{"id":"T4","span":{"begin":120,"end":127},"obj":"CI"},{"id":"T5","span":{"begin":134,"end":145},"obj":"CI"},{"id":"T6","span":{"begin":2455,"end":2462},"obj":"CI"},{"id":"T7","span":{"begin":2196,"end":2203},"obj":"CI"},{"id":"T8","span":{"begin":1343,"end":1350},"obj":"CI"},{"id":"T9","span":{"begin":1310,"end":1317},"obj":"CI"},{"id":"T25","span":{"begin":497,"end":517},"obj":"DP"}],"text":"Subgroup analysis in RAISE: a randomized, double-blind phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab or placebo in patients with metastatic colorectal carcinoma progression.\nBACKGROUND: The RAISE phase III clinical trial demonstrated that ramucirumab + FOLFIRI improved overall survival (OS) [hazard ratio (HR) = 0.844, P = 0.0219] and progression-free survival (PFS) (HR = 0.793, P \u003c 0.0005) compared with placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients previously treated with first-line bevacizumab, oxaliplatin, and a fluoropyrimidine. Since some patient or disease characteristics could be associated with differential efficacy or safety, prespecified subgroup analyses were undertaken. This report focuses on three of the most relevant ones: KRAS status (wild-type versus mutant), age (\u003c65 versus ≥65 years), and time to progression (TTP) on first-line therapy (\u003c6 versus ≥6 months).\nPATIENTS AND METHODS: OS and PFS were evaluated by the Kaplan-Meier analysis, with HR determined by the Cox proportional hazards model. Treatment-by-subgroup interaction was tested to determine whether treatment effect was consistent between subgroup pairs.\nRESULTS: Patients with both wild-type and mutant KRAS benefited from ramucirumab + FOLFIRI treatment over placebo + FOLFIRI (interaction P = 0.526); although numerically, wild-type KRAS patients benefited more (wild-type KRAS: median OS = 14.4 versus 11.9 months, HR = 0.82, P = 0.049; mutant KRAS: median OS = 12.7 versus 11.3 months, HR = 0.89, P = 0.263). Patients with both longer and shorter first-line TTP benefited from ramucirumab (interaction P = 0.9434), although TTP \u003c6 months was associated with poorer OS (TTP ≥6 months: median OS = 14.3 versus 12.5 months, HR = 0.86, P = 0.061; TTP \u003c6 months: median OS = 10.4 versus 8.0 months, HR = 0.86, P = 0.276). The subgroups of patients ≥65 versus \u003c65 years also derived a similar ramucirumab survival benefit (interaction P = 0.9521) (≥65 years: median OS = 13.8 versus 11.7 months, HR = 0.85, P = 0.156; \u003c65 years: median OS = 13.1 versus 11.9 months, HR = 0.86, P = 0.098). The safety profile of ramucirumab + FOLFIRI was similar across subgroups.\nCONCLUSIONS: These analyses revealed similar efficacy and safety among patient subgroups with differing KRAS mutation status, longer or shorter first-line TTP, and age. Ramucirumab is a beneficial addition to second-line FOLFIRI treatment for a wide range of patients with mCRC.\nTRIAL REGISTRATION: ClinicalTrials.gov, NCT01183780."}

{"project":"Linmchun_800_3","denotations":[{"id":"T1","span":{"begin":74,"end":84},"obj":"CI"},{"id":"T10","span":{"begin":462,"end":469},"obj":"CI"},{"id":"T11","span":{"begin":284,"end":295},"obj":"CI"},{"id":"T12","span":{"begin":298,"end":305},"obj":"CI"},{"id":"T13","span":{"begin":1343,"end":1350},"obj":"CI"},{"id":"T14","span":{"begin":2196,"end":2203},"obj":"CI"},{"id":"T15","span":{"begin":2182,"end":2193},"obj":"CI"},{"id":"T16","span":{"begin":2455,"end":2462},"obj":"CI"},{"id":"T17","span":{"begin":2403,"end":2414},"obj":"CI"},{"id":"T18","span":{"begin":1296,"end":1307},"obj":"CI"},{"id":"T19","span":{"begin":1654,"end":1665},"obj":"CI"},{"id":"T2","span":{"begin":86,"end":98},"obj":"CI"},{"id":"T20","span":{"begin":1964,"end":1975},"obj":"CI"},{"id":"T21","span":{"begin":2507,"end":2511},"obj":"DP"},{"id":"T22","span":{"begin":519,"end":523},"obj":"DP"},{"id":"T24","span":{"begin":185,"end":205},"obj":"DP"},{"id":"T25","span":{"begin":497,"end":517},"obj":"DP"},{"id":"T3","span":{"begin":104,"end":118},"obj":"CI"},{"id":"T4","span":{"begin":120,"end":127},"obj":"CI"},{"id":"T5","span":{"begin":134,"end":145},"obj":"CI"},{"id":"T6","span":{"begin":149,"end":156},"obj":"CI"},{"id":"T7","span":{"begin":452,"end":459},"obj":"CI"},{"id":"T8","span":{"begin":1333,"end":1340},"obj":"CI"},{"id":"T9","span":{"begin":1310,"end":1317},"obj":"CI"}],"text":"Subgroup analysis in RAISE: a randomized, double-blind phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab or placebo in patients with metastatic colorectal carcinoma progression.\nBACKGROUND: The RAISE phase III clinical trial demonstrated that ramucirumab + FOLFIRI improved overall survival (OS) [hazard ratio (HR) = 0.844, P = 0.0219] and progression-free survival (PFS) (HR = 0.793, P \u003c 0.0005) compared with placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients previously treated with first-line bevacizumab, oxaliplatin, and a fluoropyrimidine. Since some patient or disease characteristics could be associated with differential efficacy or safety, prespecified subgroup analyses were undertaken. This report focuses on three of the most relevant ones: KRAS status (wild-type versus mutant), age (\u003c65 versus ≥65 years), and time to progression (TTP) on first-line therapy (\u003c6 versus ≥6 months).\nPATIENTS AND METHODS: OS and PFS were evaluated by the Kaplan-Meier analysis, with HR determined by the Cox proportional hazards model. Treatment-by-subgroup interaction was tested to determine whether treatment effect was consistent between subgroup pairs.\nRESULTS: Patients with both wild-type and mutant KRAS benefited from ramucirumab + FOLFIRI treatment over placebo + FOLFIRI (interaction P = 0.526); although numerically, wild-type KRAS patients benefited more (wild-type KRAS: median OS = 14.4 versus 11.9 months, HR = 0.82, P = 0.049; mutant KRAS: median OS = 12.7 versus 11.3 months, HR = 0.89, P = 0.263). Patients with both longer and shorter first-line TTP benefited from ramucirumab (interaction P = 0.9434), although TTP \u003c6 months was associated with poorer OS (TTP ≥6 months: median OS = 14.3 versus 12.5 months, HR = 0.86, P = 0.061; TTP \u003c6 months: median OS = 10.4 versus 8.0 months, HR = 0.86, P = 0.276). The subgroups of patients ≥65 versus \u003c65 years also derived a similar ramucirumab survival benefit (interaction P = 0.9521) (≥65 years: median OS = 13.8 versus 11.7 months, HR = 0.85, P = 0.156; \u003c65 years: median OS = 13.1 versus 11.9 months, HR = 0.86, P = 0.098). The safety profile of ramucirumab + FOLFIRI was similar across subgroups.\nCONCLUSIONS: These analyses revealed similar efficacy and safety among patient subgroups with differing KRAS mutation status, longer or shorter first-line TTP, and age. Ramucirumab is a beneficial addition to second-line FOLFIRI treatment for a wide range of patients with mCRC.\nTRIAL REGISTRATION: ClinicalTrials.gov, NCT01183780."}