Monotherapy Administration of Sorafenib in Patients With Non–Small Cell Lung Cancer (MISSION) Trial

• Published in: Journal of thoracic oncology 2015-12, Vol.10 (12), p.1745-1753
• Main Authors: Paz-Ares, Luis, Hirsh, Vera, Zhang, Li, de Marinis, Filippo, Yang, James Chih-Hsin, Wakelee, Heather A., Seto, Takashi, Wu, Yi-Long, Novello, Silvia, Juhász, Erszébet, Arén, Osvaldo, Sun, Yan, Schmelter, Thomas, Ong, Teng Jin, Peña, Carol, Smit, Egbert F., Mok, Tony S.
• Format: Article
• Language: English
• Subjects: EGFR mutation; KRAS mutation; Molecular targeted therapy; Non-small-cell lung cancer; Sorafenib
• ISSN: 1556-0864
• DOI: 10.1097/JTO.0000000000000693

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.