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.

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 in patients 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.

• Authors: Tony S K Mok, Sang-We Kim, Yi-Long Wu, Kazuhiko Nakagawa, Jin-Ji Yang, Myung-Ju Ahn, Jie Wang, James Chih-Hsin Yang, You Lu, Shinji Atagi, Santiago Ponce, Xiaojin Shi, Yuri Rukazenkov, Vincent Haddad, Kenneth S Thress, Jean-Charles Soria
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 35 Issue 36 Pg. 4027-4034 (Dec 20 2017) ISSN: 1527-7755 [Electronic] United States
• PMID: 28968167 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Biomarkers, Tumor
• Placebos
• Quinazolines
• Pemetrexed
• EGFR protein, human
• ErbB Receptors
• Cisplatin
• Gefitinib

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (blood)
• Brain Neoplasms (secondary)
• Carcinoma, Non-Small-Cell Lung (blood, drug therapy, enzymology, genetics)
• Cisplatin (administration & dosage)
• Disease-Free Survival
• ErbB Receptors (blood, genetics)
• Female
• Gefitinib
• Humans
• Lung Neoplasms (blood, drug therapy, enzymology, genetics)
• Male
• Middle Aged
• Mutation
• Pemetrexed (administration & dosage)
• Placebos
• Quinazolines (administration & dosage)
• Survival Rate