Table 2 Targeted therapeutic agents in NSCLC

First Generation TKI

Gefitinib

EGFR (reversable)

AstraZeneca

Approved for a restricted group of patients

Erlotinib

EGFR

(reversable)

OSI, Genentec and Roche

Approved

Second Generation TKI

EKB-569

EGFR (irreversible)

Wyeth

Phase II

CL-387,785

EGFR

(irreversible)

Wyeth

Preclinical

Multi-Targeted TKI

HKI-272

EGFR, HER2

(irreversible)

Wyeth

Phase I/II

Canertinib

EGFR, HER2, HER4

(irreversible)

Pfizer Inc.

Phsae II

BIBW 2992

EGFR, HER2

(irreversible)

Boehringer Ingelheim

Phase I/II

HKI-357

EGFR, HER2

(irreversible)

Wyeth

Preclinical

Vandetanib, ZD-6474

EGFR, HER2, FLT1, KDR

(reversible)

AtraZeneca

Phase III

XL647

EGFR, HER2, KDR, EPHB4

(reversible)

Exelexis

Phase II

HER2 Heterodimerization

BMS-599626

EGFR, HER2

Bristol-Myers Squibb

Phase I

Macrolide Derivatives

RAD001

mTOR

Novartis Pharma AG

Phase II

CCI-779

mTOR

Wyeth

Phase II

AP23573

mTOR

Ariad Pharmaceuticals

Phase I

Monoclonal Antibodies

Cetuximab

EGFR

(chimeric mAB)

ImClone/Merk KGaA Bristol-Myers Squibb

Approved

Matuzumab

EGFR

(humanized mAb)

Merck KgaA

Phase II

Panitumumab

EGFR

(humanized mAb)

Abgenix

Phase II/III,

Trastuzumab

HER2

(humanized mAb)

Genentech/Roche

Approved

Bevacizumab

VEGF-A

Genentech

Approved

VEGF Inhibitors

Sorafenib

VEGFR2, FLT3, PDGFR, fibroblast growth factor receptor-1

Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals

Phase III

Sunitinib

c-kit, VEGFR1-3, PDGFRa, PDGFRb, Flt-3, CSF-1R, ret

Pfizer Inc.

Phase II/III

Axitinib AG013736

VEGF 1-3, PDGFR, cKIT

Pfizer Inc.

phase II

Regeneron

VEGF-Trap

Phase I

Non VEGF Angiogenesis inhibitors

Celecoxib

COX-2

Pfizer Inc.

Phase II

Proteasome Inhibitors

Bortezomib

Inhibits 26S proteasome

Millennium Pharmaceuticals, Inc.

Phase II

Retinoic Acid Receptor

Bexarotene

Retinoid × receptor

Eisai Inc.

Phase III