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
DOI/URL:
Notes: Article -- Export Date: 2 January 2018 -- Source: Scopus
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Citation Impact
MSK Authors
  1. Robert J Young
    206 Young
  2. Helena Alexandra Yu
    244 Yu
  3. Kathryn Beal
    219 Beal
  4. Gregory J Riely
    571 Riely
  5. Linda Su Hyun Ahn
    23 Ahn
  6. Mark Kris
    847 Kris
  7. Mariza Daras
    27 Daras
  8. Sara Anne Hayes
    33 Hayes
  9. Ai   Ni
    99 Ni
  10. Kathryn Cecilia Arbour
    74 Arbour