Abstract
Purpose
Early administration of both epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy and cytotoxic chemotherapy is crucial for non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. We investigated the effect of first-line administration of these therapies on subsequent therapy in NSCLC patients.
Methods
This study enrolled 63 consecutive patients with advanced EGFR-mutant NSCLC and good performance status (PS) and who underwent first-line EGFR-TKI therapy or standard cytotoxic chemotherapy and then had progressive disease, from 2007 to 2011. The ability of each patient to receive the other therapy after first-line treatment failure was assessed.
Results
In the first-line setting, 23 and 40 patients received EGFR-TKI therapy and cytotoxic chemotherapy, respectively. At relapse, the EGFR-TKI therapy group showed more frequent PS deterioration (p = 0.042) and greater likelihood of symptomatic central nervous system (CNS) relapse (p = 0.093) compared with the cytotoxic chemotherapy group. Nine (39 %) of 23 patients initially receiving EGFR-TKI therapy could not receive standard cytotoxic therapy after progression mainly due to symptomatic CNS relapse. Only one (3 %) of 40 initially treated with cytotoxic chemotherapy failed to receive subsequent EGFR-TKI therapy (p < 0.001). Multivariate analysis revealed a correlation between the first-line therapy and the failure to switch to the other therapy after disease progression (OR 48.605, p = 0.005).
Conclusion
In this study, patients who could not receive both EGFR-TKI therapy and cytotoxic chemotherapy in the early-line setting were included more in the first-line EGFR-TKI group, suggesting a potential risk associated with missing the timing of administration of subsequent therapy. Further investigation is warranted to detect their pretreatment clinical or molecular characteristics for development of a new treatment strategy specific for such subpopulation.
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Acknowledgments
The interpretation and reporting of these data are the sole responsibility of the authors. YK and KH had full access to all of the data in the study, were responsible for the integrity of the data and accuracy of the data analysis, and contributed to the study design, data collection, analyses, and manuscript writing. EI, NN, and TK contributed to the data collection and manuscript writing. All other co-authors contributed to the manuscript writing.
Conflict of interest
K.H. has received honoraria from Pfizer, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, and Sanofi-Aventis. N.T. has received honoraria from Chugai Pharmaceutical, AstraZeneca, Taiho Pharmaceutical, and Sanofi-Aventis. T.K. has received honoraria from Pfizer, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Kyowa Hakko Kirin, and AstraZeneca. N.N. has received honoraria from Pfizer, Daiichi-Sankyo Pharmaceutical, Kyowa Hakko Kirin, AstraZeneca, Dainippon Sumitomo Pharmaceutical, Sanofi-Aventis, Eli Lilly Japan, Taiho Pharmaceutical, and Chugai Pharmaceutical. M.T. has received honoraria from Pfizer, Eli Lilly Japan, Taiho Pharmaceutical, and Chugai Pharmaceutical. K.K. has received honoraria from Eli Lilly Japan, Nihon Kayaku, AstraZeneca, Daiichi-Sankyo Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, and Sanofi-Aventis. All other authors declared no conflicts of interest regarding this study.
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Kato, Y., Hotta, K., Takigawa, N. et al. Factor associated with failure to administer subsequent treatment after progression in the first-line chemotherapy in EGFR-mutant non-small cell lung cancer: Okayama Lung Cancer Study Group experience. Cancer Chemother Pharmacol 73, 943–950 (2014). https://doi.org/10.1007/s00280-014-2425-9
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DOI: https://doi.org/10.1007/s00280-014-2425-9