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J Thorac Oncol. 2015 Dec;10(12):1745-53. doi: 10.1097/JTO.0000000000000693.

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.

Author information

1
Instituto de Investigaciones Biomédicas de Sevilla, Hospital Universitario Virgen del Rocío/Universidad de Sevilla/CSIC, Seville, Spain. Electronic address: lpazaresr@seom.org.
2
Department of Oncology, McGill University Health Centre, Montreal, QC, Canada.
3
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
4
Pulmonary Oncological First Unit, Azienda Ospedaliera S. Camillo Forlanini, Rome, Italy.
5
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
6
Department of Medicine, Division of Oncology, Stanford University Cancer Center, Stanford, California.
7
Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
8
Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
9
Department of Clinical & Biological Sciences, University of Turin, Turin, Italy.
10
Department of Pulmonology XIV, Koranyi National Institute of TB and Pulmonology I and XIV, Budapest, Hungary.
11
Unidad de Oncologia Tocacica, International Center of Clinical Studies, Santiago, Chile.
12
Cancer Hospital/Institute, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
13
Bayer Pharma AG, Berlin, Germany.
14
Bayer HealthCare Pharmaceuticals, Whippany, New Jersey.
15
Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
16
Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China.

Abstract

INTRODUCTION:

Sorafenib monotherapy has shown benefits in phase II trials as third-/fourth-line treatment in patients with non-small-cell lung cancer (NSCLC).

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

Third-/fourth-line sorafenib therapy did not significantly increase OS in patients with relapsed/refractory NSCLC, despite significantly increasing PFS.

KEYWORDS:

EGFR mutation; KRAS mutation; Molecular targeted therapy; Non-small-cell lung cancer; Sorafenib

PMID:
26743856
DOI:
10.1097/JTO.0000000000000693
[Indexed for MEDLINE]
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