LBA33_PR - Monotherapy Administration of Sorafenib in Patients with Non-Small Cell Lung Cancer: Phase III, Randomized, Double-Blind, Placebo-Controlled MISSION...

Date 01 October 2012
Event ESMO Congress 2012
Session NSCLC metastatic, II
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Luis Paz-Ares
Authors L. Paz-Ares1, V. Hirsh2, L. Zhang3, F. De Marinis4, J. Yang5, H. Wakelee6, T. Seto7, T. Schmelter8, T.J. Ong9, T.S.K. Mok10, E.F. Smit11
  • 1Hospital Virgen del Roc, 41020 - Seville/ES
  • 2Oncology, McGill University Health Centre, H3A 1A1 - Montreal/CA
  • 3State Key Laboratory Of Oncology In South China, Sun Yat-sen University Cancer Center, 510060 - Guangzhou/CN
  • 41 Unità Operativa Di Pneumologia Oncologica, Azienda Ospedaliera S. Camillo Forlanini, IT-00151 - Rome/IT
  • 5Department Of Oncology, National Taiwan University Hospital, TW-100 - Taipei/TW
  • 6Medicine, Stanford University Cancer Center, 94305 - Stanford/US
  • 7Thoracic Oncology, National Kyushu Cancer Center, 811-1395 - Fukuoka/JP
  • 8Oncology, Bayer HealthCare, 13353 - Berlin/DE
  • 9Statistics, Bayer HealthCare Pharmaceuticals, 07045 - Montville/US
  • 10Department Of Clinical Oncology, State Key Laboratory of Southern China, The Chinese University of Hong Kong, Sha Tin, Hong Kong/CN
  • 11Dept. Of Pulmonary Diseases, Vrije University Medical Centre (VUMC), NL-1081 HV - Amsterdam/NL

 

Abstract

Background: Sorafenib monotherapy showed activity in a randomized discontinuation phase II trial of patients with advanced NSCLC who failed 2–3 chemotherapy regimens (ECOG 2501). The Phase III MISSION trial assessed whether 3rd- or 4th-line treatment with sorafenib plus best supportive care (BSC) would improve overall survival (OS), relative to placebo plus BSC, in patients with advanced relapsed/refractory NSCLC of predominantly non-squamous histology.

Methods: Eligible patients were randomized 1:1 to oral sorafenib (S) 400 mg bid or placebo (P) and stratified by geographic region, number of prior lines of treatment, brain metastases, and prior anti-EGFR therapy. The primary endpoint was OS; secondary endpoints included progression free survival (PFS), time to progression (TTP), overall response rate (ORR), disease control rate (DCR), and safety; endpoints were tested with one-sided significance level of 0.025.

Results: A total of 703 patients were randomized (S=350; P=353). Baseline demographic factors and prior treatments were generally balanced, with minor imbalances (S vs P) in female gender (47% vs 41%) and never smokers (46% vs 38%). Fewer patients received post-progression therapy in the S arm (44%) than in the P arm (56%). Assessment of OS was based on a total of 579 events (S=285, P=294). Median OS was similar in the two groups (248 vs 253 d; HR 0.99, p=0.4687), whereas median PFS (84 vs 43 d; HR 0.61; p<0.0001), TTP (89 vs 43 d; HR 0.54; p<0.0001), ORR (4.9% vs 0.9%; p<0.001) and DCR (47% vs 25%; p<0.0001) were significantly greater in the S group. Median duration of treatment was longer (12.0 vs 6.3 weeks) and dose reductions (35% vs 6%) and dose interruptions (52% vs 19%) higher in the S group. Rates of all (99% vs 91%) and serious (39% vs 32%) adverse events were higher in the S group.

Conclusion: The phase III MISSION trial did not meet its primary endpoint of improving OS as 3rd- or 4th-line treatment in patients with advanced NSCLC. Sorafenib treatment significantly enhanced PFS, TTP, ORR, and DCR compared to BSC alone. Safety and tolerability data were as expected.

Supported by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals.