Twice weekly pulse and daily continuous-dose erlotinib as initial treatment for patients with epidermal growth factor receptor-mutant lung cancers and brain metastases.

Abstract

BACKGROUND:

In a phase 1 study of pulse/continuous-dose erlotinib, no patient had disease progression in the central nervous system (CNS). This expansion cohort of the phase 1 study tested the same regimen in a cohort of individuals with epidermal growth factor receptor (EGFR)-mutant lung cancers with untreated brain metastases.

METHODS:

Patients had not received EGFR tyrosine kinase inhibitors or radiation for brain metastases. All received 1200 mg of erlotinib on days 1 and 2 and 50 mg on days 3 to 7 weekly. The primary endpoints were the overall and CNS response rates (according to version 1.1 of the Response Evaluation Criteria in Solid Tumors).

RESULTS:

Between May 2015 and August 2016, 19 patients were enrolled. Forty-two percent of the patients had target brain lesions, and the median size of the target brain lesions was 13 mm. Overall, 14 patients (74%; 95% confidence interval [CI], 51%-89%) had partial responses. The response rate in brain metastases was 75%. The overall median progression-free survival was 10 months (95% CI, 7 months to not reached). Only 3 patients (16%) had CNS progression. To date, 4 patients required CNS radiation at some time during their course. The adverse events (any grade) seen in 10% or more of the patients were rash, diarrhea, nausea, an increase in alanine aminotransferase, and fatigue.

CONCLUSIONS:

Pulse/continuous-dose erlotinib produced a 74% overall response rate and a 75% response rate in brain metastases in patients with EGFR-mutant lung cancers and untreated brain metastases. CNS control persisted even after progression elsewhere. Although this regimen did not improve progression-free survival or delay the emergence of EGFR T790M, it prevented progression in the brain and could be useful in situations in which CNS control is critical. Cancer 2018;124:105-9. © 2017 American Cancer Society.

• Authors: Kathryn C Arbour, Mark G Kris, Gregory J Riely, Ai Ni, Kathryn Beal, Mariza Daras, Sara A Hayes, Robert J Young, Christopher R Rodriguez, Linda Ahn, William Pao, Helena A Yu
• Journal: Cancer (Cancer) Vol. 124 Issue 1 Pg. 105-109 (Jan 01 2018) ISSN: 1097-0142 [Electronic] United States
• PMID: 28940498 (Publication Type: Journal Article)
• Copyright: © 2017 American Cancer Society.

Chemical References

• Protein Kinase Inhibitors
• Erlotinib Hydrochloride
• EGFR protein, human
• ErbB Receptors

Topics

• Adenocarcinoma (drug therapy, genetics, radiotherapy, secondary)
• Aged
• Aged, 80 and over
• Brain Neoplasms (drug therapy, genetics, radiotherapy, secondary)
• Cranial Irradiation (statistics & numerical data)
• Disease-Free Survival
• ErbB Receptors (genetics)
• Erlotinib Hydrochloride (administration & dosage)
• Female
• Humans
• Lung Neoplasms (drug therapy, genetics, pathology)
• Male
• Middle Aged
• Mutation
• Protein Kinase Inhibitors (administration & dosage)
• Response Evaluation Criteria in Solid Tumors
• Treatment Outcome
• Tumor Burden