Molecularly Targeted Therapy for Lung Cancer: Recent Topics

Nagahiro Saijo

doi:10.6058/jlc.2008.7.1.1

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Saijo: Molecularly Targeted Therapy for Lung Cancer: Recent Topics

Original Article

J Lung Cancer 2008;7(1):1-8.

Published online: 10 January 2008

DOI: https://doi.org/10.6058/jlc.2008.7.1.1

Molecularly Targeted Therapy for Lung Cancer: Recent Topics

Nagahiro Saijo, M.D., Ph.D.

National Cancer Center Hospital East, Chiba, Japan

Address for correspondence Nagahiro Saijo, M.D., Ph.D. National Cancer Center Hospital East, Kashiwanoha 6-5-1, Kashiwa-shi, Chiba 277-8577, Japan Tel: 81-4-7134-6902 Fax: 81-4-7131-3212 E-mail: nsaijo@east.ncc.go.jp

Received 13 January 2008 Accepted 22 May 2008

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Many clinical trials of molecular target drugs have been done against advanced lung cancer, however, majority did not meet the primary endpoint. Positive studies of EGFR-TKI such as BR21 and Interest used unselected populations of non-small cell lung cancer. It was quite difficult to explain why they were positive. In the present review, the difficulties of clinical trial design in molecular target drugs were discussed based on the differences of the magnitude of antitumor activity and the target tumor cell population between cytotoxic drugs and molecular target therapy.

Keywords: Lung cancer, Molecular target therapy, EGFR-TKI, Clinical trial

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Figures and Tables

Fig. 1.

Improvement of treatment quality.

Fig. 2.

Difference in the effect of cytotoxic drugs and molecular target drugs (waterfall plots).

Fig. 3.

Trial V15–32: Phase III trial of gefitinib vs. docetaxel in 2 ^nd/3 ^rd line NSCLC.

Fig. 4.

Treatment effect at each time point. Analysed by Prof. Masahiro Takeuchi, Kitasato University, Division of Biostatistics & Division of Pharmaceutical Medicine. Courtesy of Prof. M. Takeuchi, Kitasato University.

Table 1.

Molecular Target-based Therapy in Lung Cancer

Specific target-based drugs	Combination	Results
Gefitinib (EGFR)	Y	Negative
	N	Negative, vs placebo
	N	Negative in Japanese, vs DTX
		Positive in Global,
Erlotinib (EGFR)	Y	vs DTX Negative
	N	Positive, vs placebo
Cetuximab (EGFR)	Y	Positive
Lonafarnib (ras)	Y	Negative
Bexarotene (RXR)	Y	Negative
Affinitac (PKCα)	Y	Negative
Sorafenib (Raf, VEGF etc)	Y	Negative
Trastuzumab	Y	Negative
Cetuximab	Y	Negative
Environment specific target-based drugs	Combination	Results
MMPI (Marimastat, Prinomastat)	Y	Negative
Bevacizumab	Y	Positive

N: No, Y: Yes

Table 2.

RCTs (Randomized Clinical Trials) of Erlotinib & Gefitinib

	Early	Stage III		Advanced
Erlotinib	RADIANT (n=945, vs. placebo, on going)		First line TALENT (n=1172, CDDP/GEM±	Relapsed BR.21 (n=731, vs. placebo, positive)
			Erlotinib, negative)
			TRIBUTE (n=1059,	TITAN (n=648, vs
			CBDCA/PTX±	DTX, on going)
			Erlotinib, negative)
			SATURN (n=850, CT
			x 4 → vs. placebo,
			on going)
Gefitinib	BR.19 (n=1242, vs. placebo, terminated)	SWOG0023 (n=840, CRT→ DTX→ gefitinib, terminated)	First line INTACT1 (n=1093, CDDP/GEM± Gefitinib, negative)	Relapsed ISEL (n=1692, vs. placebo, negative)
	Japanese trial (n=670, vs. placebo, terminated)		INTACT2 (n=1037, CBDCA/PTX± Gefitinib, negative)	V15–32 (n=484, vs. DTX, negative)
				INTEREST
				(n=1466, vs.
				DTX, positive)

Table 3.

Overall Survival (ITT)

	Gefitinib RR		Docetaxel RR
No. of Pts	245	22.5%	244	12.8%
No. of events	156		150
One year survival (%)	48%		54%

Hazard ratio=1.12 (0.89∼1.40) p=0.330. Non-inferiority could not be demonstrated.

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