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.

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