Reference Detail

Ref Type Journal Article
PMID (26743856)
Authors Paz-Ares L, Hirsh V, Zhang L, de Marinis F, Yang JC, Wakelee HA, Seto T, Wu YL, Novello S, Juhász E, Arén O, Sun Y, Schmelter T, Ong TJ, Peña C, Smit EF, Mok TS
Title Monotherapy Administration of Sorafenib in Patients With Non-Small Cell Lung Cancer (MISSION) Trial: A Phase III, Multicenter, Placebo-Controlled Trial of Sorafenib in Patients with Relapsed or Refractory Predominantly Nonsquamous Non-Small-Cell Lung Cancer after 2 or 3 Previous Treatment Regimens.
Journal Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Vol 10
Issue 12
Date 2015 Dec
URL
Abstract Text Sorafenib monotherapy has shown benefits in phase II trials as third-/fourth-line treatment in patients with non-small-cell lung cancer (NSCLC).The phase III, multinational, double-blind, placebo-controlled Monotherapy admInistration of Sorafenib in patientS wIth nOn-small-cell luNg cancer (MISSION) trial randomized patients with advanced relapsed/refractory NSCLC, following two or three prior treatment regimens, to sorafenib 400 mg twice a day (n = 350) or matching placebo (n = 353) plus best supportive care. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS) and time to progression. Epidermal growth factor receptor and KRAS mutation status was analyzed in archival tumor and/or circulating tumor DNA from blood samples obtained during screening.Median OS was similar in the sorafenib and placebo groups (8.2 versus 8.3 mo; hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.84-1.17; p = 0.47). Median PFS (2.8 versus 1.4 mo; HR, 0.61; 95% CI, 0.51-0.72; p < 0.0001), and time to progression (2.9 versus 1.4 mo; HR, 0.54; 95% CI, 0.45-0.65; p < 0.0001) were significantly greater with sorafenib than with placebo. Among the 89 patients with epidermal growth factor receptor mutations, OS (13.9 versus 6.5 mo; HR, 0.48; 95% CI, 0.30-0.76; p = 0.002) and PFS (2.7 versus 1.4 mo; HR, 0.27; 95% CI, 0.16-0.46; p < 0.001) were significantly higher with sorafenib than placebo. PFS was significantly longer with sorafenib than placebo in patients with either wild-type or mutated KRAS, but OS was similar. Common drug-related adverse events were rash/desquamation, diarrhea, and fatigue, consistent with the safety profile of sorafenib.Third-/fourth-line sorafenib therapy did not significantly increase OS in patients with relapsed/refractory NSCLC, despite significantly increasing PFS.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Therapy Description
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KRAS mutant non-small cell lung carcinoma sensitive Sorafenib Phase II Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in comparable 8-week disease control rate in KRAS wild-type (47%, 20/43) and KRAS mutated (44%, 8/18) patients with advanced non-small cell lung carcinoma (PMID: 27480147). 27480147
KRAS mutant non-small cell lung carcinoma sensitive Sorafenib Phase III Actionable In a Phase III trial, treatment with Nexavar (sorafenib) resulted in a longer progression free survival in patients with KRAS-mutant non-small cell lung cancer when compared to placebo, however, overall survival was similar between the two arms (PMID: 26743856). 26743856
KRAS mutant non-small cell lung carcinoma sensitive Sorafenib Phase II Actionable In a Phase II trial, treatment with Nexavar (sorafenib) resulted in partial response in 8.8% (5/57) and stable disease in 43.8% (25/57) of patients with KRAS-mutant non-small cell lung cancer (PMID: 23224737). 23224737
KRAS wild-type non-small cell lung carcinoma no benefit Sorafenib Phase III Actionable In a Phase III trial, Nexavar (sorafenib) treatment in KRAS wild-type non-small cell lung carcinoma patients did not meet its primary endpoint when compared to placebo, resulting in a similar overall survival, however, did meet its secondary endpoint, showing a longer progression free survival (PMID: 26743856). 26743856
Unknown unknown non-small cell lung carcinoma no benefit Sorafenib Phase III Actionable In a Phase III trial, Nexavar (sorafenib) treatment in non-small cell lung carcinoma patients did not reach its primary endpoint, resulting in an overall survival similar to that when treated with placebo, however, did meet its secondary endpoint, demonstrating a greater progression free survival and time to progression when compared to placebo (PMID: 26743856). 26743856