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

Luis Paz-Ares, Vera Hirsh, Li Zhang, Filippo De Marinis, James Chih Hsin Yang, Heather A. Wakelee, Takashi Seto, Yi Long Wu, Silvia Novello, Erszébet Juhász, Osvaldo Arén, Yan Sun, Thomas Schmelter, Teng Jin Ong, Carol Penã, Egbert F. Smit, Tony S. Mok

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1745-1753
Number of pages9
JournalJournal of Thoracic Oncology
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 1 2015

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Non-Small Cell Lung Carcinoma
Placebos
Disease-Free Survival
Confidence Intervals
Survival
Therapeutics
Epidermal Growth Factor Receptor
sorafenib
Mutation
Exanthema
Drug-Related Side Effects and Adverse Reactions
Fatigue
Diarrhea
Neoplasms
Safety
DNA

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

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. / 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; Penã, Carol; Smit, Egbert F.; Mok, Tony S.

In: Journal of Thoracic Oncology, Vol. 10, No. 12, 01.12.2015, p. 1745-1753.

Research output: Contribution to journalArticle

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 ; Penã, Carol ; Smit, Egbert F. ; Mok, Tony S. / 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. In: Journal of Thoracic Oncology. 2015 ; Vol. 10, No. 12. pp. 1745-1753.
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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.",
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TY - JOUR

T1 - Monotherapy Administration of Sorafenib in Patients with Non-Small Cell Lung Cancer (MISSION) Trial

T2 - 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

AU - Paz-Ares, Luis

AU - Hirsh, Vera

AU - Zhang, Li

AU - De Marinis, Filippo

AU - Yang, James Chih Hsin

AU - Wakelee, Heather A.

AU - Seto, Takashi

AU - Wu, Yi Long

AU - Novello, Silvia

AU - Juhász, Erszébet

AU - Arén, Osvaldo

AU - Sun, Yan

AU - Schmelter, Thomas

AU - Ong, Teng Jin

AU - Penã, Carol

AU - Smit, Egbert F.

AU - Mok, Tony S.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - EGFR mutation

KW - KRAS mutation

KW - Molecular targeted therapy

KW - Non-small-cell lung cancer

KW - Sorafenib

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