Bevacizumab, Pemetrexed, and Cisplatin, or Bevacizumab and Erlotinib for Patients With Advanced Non-Small-Cell Lung Cancer Stratified by Epidermal Growth Factor Receptor Mutation: Phase II Trial SAKK19/09.

Details

Serval ID
serval:BIB_3E5D55F50AAE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Bevacizumab, Pemetrexed, and Cisplatin, or Bevacizumab and Erlotinib for Patients With Advanced Non-Small-Cell Lung Cancer Stratified by Epidermal Growth Factor Receptor Mutation: Phase II Trial SAKK19/09.
Journal
Clinical Lung Cancer
Author(s)
Gautschi O., Mach N., Rothschild S.I., Li Q., Stahel R.A., Zippelius A., Cathomas R., Früh M., Betticher D.C., Peters S., Rauch D., Feilchenfeldt J., Bubendorf L., Savic S., Jaggi R., Leibundgut E.O., Largiadèr C., Brutsche M., Pilop C., Stalder L., Pless M., Ochsenbein A.F.
Working group(s)
Swiss Group for Clinical Cancer Research
ISSN
1938-0690 (Electronic)
ISSN-L
1525-7304
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
16
Number
5
Pages
358-365
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
OBJECTIVE: The goal was to demonstrate that tailored therapy, according to tumor histology and epidermal growth factor receptor (EGFR) mutation status, and the introduction of novel drug combinations in the treatment of advanced non-small-cell lung cancer are promising for further investigation.
METHODS: We conducted a multicenter phase II trial with mandatory EGFR testing and 2 strata. Patients with EGFR wild type received 4 cycles of bevacizumab, pemetrexed, and cisplatin, followed by maintenance with bevacizumab and pemetrexed until progression. Patients with EGFR mutations received bevacizumab and erlotinib until progression. Patients had computed tomography scans every 6 weeks and repeat biopsy at progression. The primary end point was progression-free survival (PFS) ≥ 35% at 6 months in stratum EGFR wild type; 77 patients were required to reach a power of 90% with an alpha of 5%. Secondary end points were median PFS, overall survival, best overall response rate (ORR), and tolerability. Further biomarkers and biopsy at progression were also evaluated.
RESULTS: A total of 77 evaluable patients with EGFR wild type received an average of 9 cycles (range, 1-25). PFS at 6 months was 45.5%, median PFS was 6.9 months, overall survival was 12.1 months, and ORR was 62%. Kirsten rat sarcoma oncogene mutations and circulating vascular endothelial growth factor negatively correlated with survival, but thymidylate synthase expression did not. A total of 20 patients with EGFR mutations received an average of 16 cycles. PFS at 6 months was 70%, median PFS was 14 months, and ORR was 70%. Biopsy at progression was safe and successful in 71% of the cases.
CONCLUSIONS: Both combination therapies were promising for further studies. Biopsy at progression was feasible and will be part of future SAKK studies to investigate molecular mechanisms of resistance.
Keywords
Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Bevacizumab/administration & dosage, Biopsy, Carcinoma, Non-Small-Cell Lung/drug therapy, Carcinoma, Non-Small-Cell Lung/genetics, Cisplatin/administration & dosage, Disease-Free Survival, Erlotinib Hydrochloride/administration & dosage, Feasibility Studies, Female, Humans, Lung Neoplasms/drug therapy, Lung Neoplasms/genetics, Male, Middle Aged, Mutation, Pemetrexed/administration & dosage, Receptor, Epidermal Growth Factor/genetics, Survival Rate
Pubmed
Web of science
Create date
22/09/2015 16:30
Last modification date
20/08/2019 13:35
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