EGFR-positive NSCLC: Gefitinib-resistant Patients Should Not Receive Chemotherapy Plus Gefitinib

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The findings demonstrate that administration of a first-generation EGFR TKI should not be continued in combination with standard chemotherapy upon progression of EGFR mutation–positive NSCLC.
The findings demonstrate that administration of a first-generation EGFR TKI should not be continued in combination with standard chemotherapy upon progression of EGFR mutation–positive NSCLC.

Continuing gefitinib treatment upon progression in patients with EGFR mutation–positive non–small cell lung cancer (NSCLC) may negatively affect overall survival (OS) and should be avoided prior to initiating chemotherapy, according to a study published in the Journal of Clinical Oncology.1

A preliminary analysis of the phase 3 IMPRESS trial (ClinicalTrials.gov Identifier: NCT01544179) demonstrated that there was no significant difference in progression-free survival (PFS), the primary endpoint of the study, among patients with NSCLC who continued first-line gefitinib upon progression compared with placebo.

For this study, 265 patients were randomly assigned to receive gefitinib 250 mg or placebo concomitantly with cisplatin 75 mg/m2 plus pemetrexed 500 mg/m2 upon disease progression. At the time of this analysis, overall data maturity was at 66%.

Median OS was significantly shorter in the gefitinib arm (13.4 months) vs the placebo arm (19.5 months; hazard ratio [HR], 1.44; 95% CI, 1.07-1.94; P = .016), and had a statistically significant detriment in patients who were T790M mutation–positive (HR, 1.49; 95% CI, 1.02-2.21) but not for patients who were T790M-negative (HR, 1.15; 95% CI, 0.68-1.94).

The findings demonstrate that administration of a first-generation EGFR TKI should not be continued in combination with standard chemotherapy upon progression of EGFR mutation–positive NSCLC. The authors added that “future investigation into the optimal management of T790M mutation-negative resistance is warranted.”

Reference

  1. Mok TS, Kim SW, Wu YL, et al. Gefitinib plus chemotherapy versus chemotherapy in epidermal growth factor receptor mutation-positive non-small-cell lung cancer resistant to first-line gefitinib (IMPRESS): overall survival and biomarker analysis. J Clin Oncol. 2017 Oct 2.  doi: 10.1200/JCO.2017.73.9250 [Epub ahead of print]

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