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  • Review Article
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Reasons for response differences seen in the V15-32, INTEREST and IPASS trials

Nature Reviews Clinical Oncology volume 6, pages 287–294 (2009)Cite this article

Abstract

The first phase III study to assess the effect of gefitinib and docetaxel on the survival of Japanese patients with non-small-cell lung cancer who received previous treatment with platinum doublets, the V15-32 trial, did not establish noninferiority of gefitinib over docetaxel in terms of the effect on overall survival, despite the results showing a twofold higher response rate to gefitinib. The overall survival favored docetaxel for the first 18 months and gefitinib thereafter. The INTEREST trial, which compared docetaxel and gefitinib, demonstrated noninferiority of gefitinib, and the survival curves were completely superimposed. In this trial, patients had been recruited from 24 countries from Europe, Asia, and North and South America. Results of the IPASS trial showed superior progression-free survival for gefitinib compared with the combination of carboplatin and paclitaxel as first-line treatment in Asian patients who were nonsmokers and had adenocarcinoma histology. In this Review, we discuss the reasons for the differences in the effects of molecular-targeted drugs and cytotoxic antineoplastic agents observed in these trials. We also highlight the magnitude of the antitumor activity of these two different categories of drugs, and discuss how this could affect future clinical trial design and analysis.

Key Points

  • Many unexpected results were observed in the randomized, controlled trials of EGFR-targeted tyrosine kinase inhibitors (TKIs)

  • The nature and quantity of antitumor effects are different between cytotoxic chemotherapy and molecular-targeted drugs

  • Selection of patients is extremely important for future clinical trials that test EGFR-TKIs

  • Results from the IPASS trial demonstrate that EGFR-TKIs provide superior progression-free survival compared with platinum-based doublet chemotherapy in selected patients with non-small-cell lung cancer, especially those with mutated EGFR

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Figure 1: Schematic diagram to show the randomization schema for the randomized phase III V15-32 trial.
Figure 2: Table showing the overall survival data for patients treated in the randomized phase III V15-32 trial.
Figure 3: Retrospective analysis of the survival data from the randomized phase III V15-32 trial.
Figure 4: Waterfall plots showing the differences in the effect of cytotoxic drugs and molecular-target drugs on tumor size.

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Acknowledgements

The authors would like to acknowledge the effort of the investigators of AstraZeneca's trials such as the V15-32 INTEREST and IPASS trials.

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Authors and Affiliations

  1. Kinki University School of Medicine, Osaka, Japan

    Nagahiro Saijo

  2. Pharmacology Division, Kitasato University, Tokyo, Japan

    Masahiro Takeuchi

  3. National Cancer Center Hospital, Tokyo, Japan

    Hideo Kunitoh

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  1. Nagahiro Saijo
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  2. Masahiro Takeuchi
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  3. Hideo Kunitoh
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Corresponding author

Correspondence to Nagahiro Saijo.

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Competing interests

N. Saijo declared he receives research support from AstraZeneca, Bristol–Myers Squibb, and Chugai–Roche. He is also on the speakers bureau for Eli Lilly. H. Kunitoh declared he is on the speakers bureau for AstraZeneca, Bristol–Myers Squibb and Sanofi–Aventis. H. Takeuchi declared no competing interests.

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Saijo, N., Takeuchi, M. & Kunitoh, H. Reasons for response differences seen in the V15-32, INTEREST and IPASS trials. Nat Rev Clin Oncol 6, 287–294 (2009). https://doi.org/10.1038/nrclinonc.2009.37

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