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

Authors: Arbour, K. C.; Kris, M. G.; Riely, G. J.; Ni, A.; Beal, K.; Daras, M.; Hayes, S. A.; Young, R. J.; Rodriguez, C. R.; Ahn, L.; Pao, W.; Yu, H. A.
Article Title: 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. © 2017 American Cancer Society
Keywords: adult; clinical article; controlled study; treatment outcome; aged; aged, 80 and over; disease-free survival; middle aged; gene mutation; human cell; genetics; mutation; disease course; fatigue; erlotinib; diarrhea; side effect; cancer radiotherapy; disease free survival; brain tumor; brain neoplasms; anorexia; adenocarcinoma; progression free survival; anemia; tumor volume; protein kinase inhibitor; mucosa inflammation; nausea; lung neoplasms; epidermal growth factor receptor; cohort analysis; lung cancer; receptor, epidermal growth factor; pathology; skull irradiation; cranial irradiation; abdominal pain; alanine aminotransferase blood level; dizziness; pruritus; rash; protein kinase inhibitors; lung tumor; tumor burden; drug response; cancer size; brain metastasis; thrombocyte count; phase 1 clinical trial; egfr gene; gastroesophageal reflux; dry eye; dry skin; alopecia; bilirubin blood level; egfr protein, human; dysgeusia; paronychia; utilization; brain metastases; hypertrichosis; secondary; hypertransaminasemia; response evaluation criteria in solid tumors; very elderly; humans; human; male; female; priority journal; article; egfr t790m; epidermal growth factor receptor (egfr); non–small cell lung cancer; erlotinib hydrochloride
Journal Title: Cancer
Volume: 124
Issue: 1
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2018-01-01
Start Page: 105
End Page: 109
Language: English
DOI: 10.1002/cncr.30990
PUBMED: 28940498
PROVIDER: scopus
PMCID: PMC5735028
Notes: Article -- Export Date: 2 January 2018 -- Source: Scopus
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MSK Authors
  1. Robert J Young
    108 Young
  2. Helena Alexandra Yu
    88 Yu
  3. Kathryn Beal
    157 Beal
  4. Gregory J Riely
    344 Riely
  5. Linda Su Hyun Ahn
    7 Ahn
  6. Mark Kris
    597 Kris
  7. Mariza Daras
    15 Daras
  8. Sara Anne Hayes
    19 Hayes
  9. Ai   Ni
    47 Ni
  10. Kathryn Cecilia Arbour
    14 Arbour