Systemic therapies in metastatic non-small-cell lung cancer with emphasis on targeted therapies: the rational approach.
Historically, first-line treatment of non-small-cell lung cancer (NSCLC) has been based on giving a limited number of cycles of chemotherapy to achieve tumour response or stable disease. Patients are then observed without active therapy until disease progresses, at which point, subsequent lines of therapy are given. In recent years, two new concepts have been introduced to the management of NSCLC: maintenance therapy and therapy with targeted agents. Maintenance therapy-with either a chemotherapeutic or biologic agent-is given immediately after first-line therapy to patients who have achieved tumour response or stable disease. Choice of therapy may include continuation of the agents included in the induction regimen or introduction of different agents (early second-line treatment) with the aim of preventing progression and prolonging progression-free survival. Targeted agents such as bevacizumab and erlotinib target critical molecular signalling pathways and provide several advantages over chemotherapy, including fewer toxicities and the possibility of a longer duration of therapy. This review examines the treatment options in all lines of therapy for metastatic NSCLC, focusing particularly on targeted therapies that have been approved in the United States, Canada, or Europe.
Hirsh
V
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Medical Oncology Department, MUHC Royal Victoria Hospital, Montreal, Quebec. vera.hirsh@muhc.mcgill.ca
Am J Pathol. 2004 Jul;165(1):35-52
15215160
Nat Rev Cancer. 2008 Aug;8(8):579-91
18596824
J Thorac Oncol. 2009 Nov;4(11 Suppl 3):S1071-3
19861922
Clin Lung Cancer. 2008 Mar;9 Suppl 2:S62-70
21885001
Science. 2005 Jan 7;307(5706):58-62
15637262
J Clin Oncol. 2004 Jun 1;22(11):2184-91
15169807
J Clin Oncol. 2009 Mar 10;27(8):1227-34
19188680
J Clin Oncol. 2000 May;18(10):2095-103
10811675
J Clin Oncol. 2008 Jul 20;26(21):3543-51
18506025
Cancer Control. 2001 Jul-Aug;8(4):326-36
11483886
Curr Oncol Rep. 2000 Jan;2(1):96-101
11122830
Clin Lung Cancer. 2009 Jul;10(4):252-6
19632943
J Thorac Oncol. 2009 Feb;4(2):243-50
19179904
N Engl J Med. 2009 Sep 3;361(10):947-57
19692680
J Clin Oncol. 2009 Jul 1;27(19):3217-24
19433683
N Engl J Med. 2005 Jul 14;353(2):123-32
16014882
N Engl J Med. 2006 Dec 14;355(24):2542-50
17167137
J Thorac Oncol. 2010 Sep;5(9):1416-23
20686429
Oncology. 2002;63(2):105-14
12239444
Ann Oncol. 2006 May;17 Suppl 5:v33-36
16807460
J Pharmacol Exp Ther. 1999 Nov;291(2):739-48
10525095
N Engl J Med. 2002 Jan 10;346(2):92-8
11784875
J Clin Oncol. 2011 Mar 10;29(8):1067-74
21282537
Cancer Res. 1997 Nov 1;57(21):4838-48
9354447
Oncology (Williston Park). 2003 Apr;17(4):457-64, 469-71; discussion 471, 478-80, 483-4
12735143
Oncologist. 2009 Feb;14(2):137-47
19190239
J Clin Oncol. 2007 Oct 20;25(30):4743-50
17909199
J Clin Oncol. 2005 Apr 10;23(11):2544-55
15753462
Curr Oncol. 2008 Dec;15(6):279-85
19079629
J Clin Oncol. 2008 Nov 20;26(33):5326-34
18854571
Oncologist. 2009 Mar;14(3):253-63
19221167
Nat Rev Cancer. 2003 Jun;3(6):401-10
12778130
J Clin Oncol. 2006 Aug 20;24(24):3831-7
16921034
J Clin Oncol. 2009 Feb 1;27(4):591-8
19075278
Lancet. 2008 Nov 22;372(9652):1809-18
19027483
J Clin Oncol. 2004 May 1;22(9):1589-97
15117980
J Thorac Oncol. 2007 Sep;2(9):845-53
17805063
Lancet. 2009 May 2;373(9674):1525-31
19410716
Expert Opin Ther Targets. 2007 Feb;11(2):245-57
17227238