New drugs in advanced non-small-cell lung cancer: searching for the correct clinical development.
BACKGROUND
Non-small-cell lung cancer (NSCLC) is one of the most active fields of research in oncology, with many drugs under clinical development. Most of these drugs offer novel mechanisms of action compared with drugs currently used in clinical practice.


METHODS
In this article, results recently obtained with most promising new drugs for advanced NSCLC are briefly described.


RESULTS
Most of the new drugs are currently being tested without a biomarker-driven selection, due to inadequate knowledge of predictive factors. A few drugs are tested in biologically selected samples of NSCLC patients. The results obtained with crizotinib in patients with ALK gene rearrangement are a good example of the speed with which biological discoveries can be translated to clinical testing.


CONCLUSIONS
Emerging clinical and molecular data demonstrate that NSCLC is a family of related but distinct diseases. Some drugs tested in unselected population will probably obtain an incremental benefit compared to the current standard, but this will not substantially change the unfavorable prognosis of NSCLC patients. By contrast, unprecedented and much more cost-effective results can be obtained when targeted agents are administered following appropriate biomarker-driven patient selection.
National Cancer Institute, Clinical Trials Unit, Via Mariano Semmola, 80131 Naples, Italy. dimaiomax@libero.it
Massimo
M
Di Maio
Alessandro
A
Morabito
Maria Carmela
MC
Piccirillo
Gennaro
G
Daniele
Pasqualina
P
Giordano
Raffaele
R
Costanzo
Marita Georgia
MG
Riccardi
Gaetano
G
Rocco
Nicola
N
Normanno
Francesco
F
Perrone
D000077716:Afatinib; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends; D055808:Drug Discovery / Q000379:methods / Q000639:trends*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D009841:Oligonucleotides; D011799:Quinazolines / Q000008:administration & dosage / Q000737:chemistry; D016032:Randomized Controlled Trials as Topic / Q000379:methods
D000970:Antineoplastic Agents; D007211:Indoles; D009841:Oligonucleotides; D011799:Quinazolines; D009536:Niacinamide; D000077716:Afatinib; C519562:imetelstat