Addition of EGFR Tyrosine Kinase Inhibitor to Chemotherapy in Resistant Non–Small Cell Lung Cancer

Key Points

  • In patients with EGFR-mutant non–small cell lung cancer, overall survival was worse in the gefitinib vs placebo groups.
  • The poorer outcome appeared to be associated with T790M-positive status.

As reported by Mok et al in the Journal of Clinical Oncology, overall survival analysis of the phase III IMPRESS trial indicated a poorer outcome when adding gefitinib (Iressa) vs placebo to chemotherapy after disease progression on first-line gefitinib in epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC). The primary analysis of the trial, reported in 2015, showed no progression-free survival benefit with the addition of gefitinib.

Study Details

In the trial, 265 patients from 61 sites in 11 European and Asia-Pacific countries were randomized between March 2012 and December 2013 to receive gefitinib at 250 mg (n = 133) or placebo (n = 132) daily plus up to 6 cycles of cisplatin at 75 mg/m2 and pemetrexed (Alimta) at 500 mg/m2; gefitinib or placebo was continued until disease progression. In the primary analysis, median progression-free survival was 5.4 months in the gefitinib group vs 5.4 months in the placebo group (hazard ratio [HR] = 0.86, P = .27).

Overall Survival

Overall survival analysis was performed when 166 deaths had occurred, as of data cutoff in November 2015. Postprogression therapy was received by 61% of the gefitinib group vs 71% of the placebo group. Median overall survival was 13.4 months vs 19.5 months (HR = 1.44, P = .016). A higher proportion of patients in the gefitinib vs placebo groups had T790M-positive plasma samples (62% vs 47%); among these patients, median overall survival was 10.8 vs 14.1 months (HR = 1.49, P = .0432); among patients without T790M mutation, median overall survival 21.4 vs 22.5 months (HR = 1.15, P = .6093). Analysis of progression-free survival according to T790M status showed similar outcomes in mutation-positive patients (HR = 0.97, P = .8829) and a nonsignificant difference in mutation-negative patients (HR = 0.67, P = .0745).

The investigators concluded: “Final [overall survival] data from IMPRESS are supportive of earlier [progression-free survival] results and are sufficient to warn physicians against the continuation of treatment with first-generation EGFR tyrosine kinase inhibitors beyond radiologic disease progression when chemotherapy is initiated. Plasma biomarker analyses suggest that this effect may be driven by T790M-positive status.”

The study was supported by AstraZeneca.

Tony S.K. Mok, MD, of The Chinese University of Hong Kong, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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