Personalized medicine and treatment approaches in non-small-cell lung carcinoma

Figures & data

Figure 1 Simplified schema of molecular pathways involved in lung cancer with proposed mechanisms of action of established and newer agents.

Table 1 Proposed mechanisms of action of drugs in clinical trials addressing K-RAS mutated tumors

Mechanism of action	Drug name	Clinical trial	Tumor characteristics
MEK inhibitor	Selumetinib/AZD6244	NCT01229150, NCT00890825, NCT01239290	k-RAS mutated NSCLC
	GSK1120212	NCT01362296, NCT00687622	k-RAS mutated NSCLC
	MEK162	NCT01337765, NCT01449058, NCT01363232, NCT00959127	Tumors with k-RAS, NRAS, and/or BRAF mutations
c-MET inhibitor	ARQ 197	NCT01395758	k-RAS mutated NSCLC
mTOR inhibitor	Retaspimycin HCl (IPI-504) +everolimus	NCT01427946	k-RAS mutated NSCLC
	Ridaforolimus	NCT00818675	k-RAS mutated NSCLC
mTor+ PI3K inhibitors	BEZ235	NCT01337765	Tumors with k-RAS, NRAS, and/or BRAF mutations
PI3K inhibitor	BYL719	NCT01449058	Tumors with k-RAS, NRAS, and/or BRAF mutations
	BKM120	NCT01363232	Tumors with k-RAS, NRAS, and/or BRAF mutations
HSP90 inhibitor	Retaspimycin HCl (IPI-504) + everolimus	NCT01427946	k-RAS mutated NSCLC
Virus killing Ras activated cells	Reovirus serotype 3-Dearing strain (REOLYSIN)	NCT00861627	k-RAS mutated NSCLC
Recombinant mutant Ras protein	GI-4000	NCT00655161	k-RAS mutated NSCLC

Table 2 Phase III studies with EGFR TKIs in the first-line setting in advanced NSCLC

Study	Population studied	Treatment arms	Results
IPASS^Citation50	Adenocarcinoma	Carboplatin/paclitaxel vs Gefitinib	Intention to treat group had a HR 0.74; 95% CI, 0.65–0.85; P < 0.001.
			EGFR mutated group had a HR =0.48; 95% CI, 0.36–0.64; P < 0.001.
			Response Rate was 71.2% vs 47.3%, (P <0.001) in the Gefitinib and chemotherapy groups respectively, within the EGFR mutated subgroup.
NEJSG 002^Citation51	EGFR activating mutation positive	Carboplatin/paclitaxel vs gefitinib	Gefitinib group had a HR = 0.30; 95% CI, 0.22–0.41; P <0.001.
			Response rate was 73.7% vs 30.7%, (P<0.001) in the Gefitinib and chemotherapy arms respectively.
WJTOG3405^Citation54	EGFR activating mutation positive	Cisplatin/docetaxel vs gefitinib	Gefitinib group had a HR = 0.489; 95% CI, 0.336–0.710; P <0.0001.
			Response rate was 62.1% vs 32.2% (P <0.0001) in the Gefitinib and chemotherapy arms respectively.
OPTIMAL (CTONG-0802)^Citation52	EGFR activating mutation positive	Gemcitabine/carboplatin vs erlotinib	Erlotinib group had a HR =0.16; 95% CI, 0.10–0.26; P <0.0001.
			Response rate was 83% vs 36% (P <0.0001) in the Erlotinib and chemotherapy arms respectively.
EURTAC^Citation53	EGFR activating mutation positive	Platinum doublet vs erlotinib	Erlotinib group had a HR, 0.80; P = 0.42.
			Response rate was 54.5% vs 10.5% (P <0.0001) in the Erlotinib and chemotherapy arms respectively.

Table 3 Current ALK inhibitors in clinical trials in various tumor types

LDK378	NCT01283516	Phase I	Tumors with ALK
IPI-504 HSP 90 inhibitor	NCT01228435	Phase II	ALK + lung cancer
AP26113 (ALK/EGFR inhibitor)	NCT01449461	Phase I/II	ALK + or EGFR + lung Ca
PF-02341066 (c-Met Alk inhibitor)	NCT00585195	Phase I	ALK + lymphoma
PF-02341066 (c-Met Alk inhibitor)	NCT00932893	Phase III	ALK + lung cancer second line

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