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Gefitinib Plus Chemotherapy in the IMPRESS Trial: Final Overall Survival

By: Bruce Cleary
Posted: Monday, December 4, 2017

Tony S.K. Mok, MD, of the Chinese University of Hong Kong, and colleagues, writing in the Journal of Clinical Oncology, reported that final, mature overall survival data from the phase III IMPRESS trial agree with earlier progression-free survival data, indicating treatment with first-generation tyrosine kinase inhibitors (TKIs) such as gefitinib should not be continued after radiologic disease progression when chemotherapy has begun. For patients with epidermal growth factor receptor (EGFR) mutation–positive non–small cell lung cancer (NSCLC) who do not respond to first-line gefitinib, continued gefitinib treatment does not optimize outcomes, according to the authors.

In the IMPRESS trial, which included 265 patients with NSCLC trial, the continuation of gefitinib along with cisplatin and pemetrexed was detrimental to overall survival when compared with placebo plus cisplatin and pemetrexed. In fact, the detriment was reported to be statistically significant in those with T790M mutation–positive plasma samples but not in those with T790M mutation–negative patients.

The patients in this trial all had acquired resistance to first-line TKIs. “To our knowledge, this article is the first to demonstrate a significant detrimental effect on overall survival with continuation with an EGFR TKI in combination with standard chemotherapy,” the investigators wrote. Continuing first-generation TKIs was often advocated by many clinicians until third-generation EGFR TKIs became available, and these findings appear to be sufficient to warn physicians against this practice.