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 analyses
Journal
Journal of Clinical Oncology
Journal Volume
35
Journal Issue
36
Pages
4027-4034
Date Issued
2017
Author(s)
Mok T.S.K
Kim S.-W
Wu Y.-L
Nakagawa K
Yang J.-J
Ahn M.-J
Wang J
Lu Y
Atagi S
Ponce S
Shi X
Rukazenkov Y
Haddad V
Thress K.S
Soria J.-C.
Abstract
Purpose: The Iressa Mutation-Positive Multicentre Treatment Beyond ProgRESsion Study (IMPRESS) compared the continuation of gefitinib plus chemotherapy with placebo plus chemotherapy in patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer with progression (Response Evaluation Criteria in Solid Tumors 1.1) after first-line gefitinib. Primary results indicated no difference between treatments in terms of progression-free survival (PFS). The current analysis presents final, mature, overall survival (OS) data, together with exploratory analyses that examined whether specific biomarkers, including T790M mutation status, were able to differentiate a relative treatment effect. Patients and Methods: Patients were randomly assigned to gefitinib 250 mg or placebo, in addition to cisplatin 75 mg/m2 plus pemetrexed 500 mg/m2 (maximum of six cycles of chemotherapy). EGFR mutation status was determined from plasma-derived circulating free tumor-derived DNA samples (beads, emulsification, amplification, and magnetics digital polymerase chain reaction assay, allelic fraction analysis). Results: A total of 265 patients with non-small-cell lung cancer were randomly assigned, and overall data maturity was 66%. Continuation of gefitinib plus cisplatin and pemetrexed was detrimental to OS when compared with placebo plus cisplatin and pemetrexed (hazard ratio [HR], 1.44; 95% CI, 1.07 to 1.94;P =.016; median OS, 13.4 v 19.5 months). The detriment was statistically significant inpatients with T790M mutation-positive plasma samples (HR, 1.49; 95% CI, 1.02 to 2.21), whereas statistical significance was not reached in T790M mutation-negative patients (HR, 1.15; 95% CI, 0.68 to 1.94). PFS in T790M mutation-positive patients was similar between treatments, and the difference observed in T790M mutation-negative patients did not reach statistical significance (HR, 0.67; 95% CI, 0.43 to 1.03; P =.0745). Conclusion: Final OS data from IMPRESS are supportive of earlier PFS 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. ? 2017 by American Society of Clinical Oncology.
SDGs
Other Subjects
cisplatin; epidermal growth factor receptor; gefitinib; pemetrexed; antineoplastic agent; cisplatin; EGFR protein, human; epidermal growth factor receptor; gefitinib; pemetrexed; placebo; quinazoline derivative; tumor marker; adult; aged; Article; brain metastasis; cancer combination chemotherapy; cancer growth; cancer resistance; controlled study; distant metastasis; female; gene mutation; human; intention to treat analysis; major clinical study; male; malignant pleura effusion; multiple cycle treatment; non small cell lung cancer; overall survival; priority journal; progression free survival; randomized controlled trial; unspecified side effect; blood; brain tumor; clinical trial; disease free survival; enzymology; genetics; lung tumor; middle aged; multicenter study; mutation; non small cell lung cancer; secondary; survival rate; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Cisplatin; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Pemetrexed; Placebos; Quinazolines; Receptor, Epidermal Growth Factor; Survival Rate
Publisher
American Society of Clinical Oncology
Type
journal article