Dosing to rash: a phase II trial of the first-line erlotinib for patients with advanced non-small-cell lung cancer an Eastern Cooperative Oncology Group Study (E3503).
BACKGROUND
The development of a rash has been retrospectively associated with increased response and improved survival when treated with erlotinib at the standard dose of 150 mg per day. The objective of this trial was to evaluate the association of the activity of erlotinib in the first-line setting in patients with advanced non-small-cell lung cancer (NSCLC) with the development of a tolerable rash via dose escalation of erlotinib or tumour characteristics.


METHODS
Patients, with advanced NSCLC without prior systemic therapy, were treated with erlotinib 150 mg orally per day. The dose was increased by 25mg every two weeks until the development of grade 2/tolerable rash or other dose limiting toxicity. Tumour biopsy specimens were required for inclusion.


RESULTS
The study enrolled 137 patients, 135 were evaluable for safety and 124 were eligible and evaluable for response. Only 73 tumour samples were available for analysis. Erlotinib dose escalation occurred in 69/124 patients. Erlotinib was well tolerated with 70% of patients developing a grade 1/2 rash and 10% developing grade 3 rash. Response rate and disease control rate were 6.5% and 41.1% respectively. Median overall survival was 7.7 months. Toxicity and tumour markers were not associated with response. Grade 2 or greater skin rash and low phosphorylated mitogen-activated protein kinase (pMAPK) were associated with improved survival.


CONCLUSIONS
Overall survival was similar in this trial compared to first-line chemotherapy in this unselected patient population. Dose escalation to the development of grade 2 skin rash was associated with improved survival in this patient population.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, United States. Electronic address: brahmju@jhmi.edu.
J R
JR
Brahmer
Dana-Farber Cancer Institute, Boston, MA, United States.
J W
JW
Lee
University of Wisconsin, Madison, WI, United States.
A M
AM
Traynor
Hospital Madrid Sanchinarro, Madrid, Spain.
M M
MM
Hidalgo
University of Wisconsin, Madison, WI, United States.
J M
JM
Kolesar
University of Pittsburgh, Pittsburgh, PA, United States.
J M
JM
Siegfried
Decatur Memorial Hospital, Decatur, IL, United States.
P P
PP
Guaglianone
Northwestern University, Chicago, IL, United States.
J D
JD
Patel
Sanford Cancer Center, Sioux Falls, SD, United States.
M D
MD
Keppen
University of Texas Southwestern Medical Center, Dallas, TX, United States.
J H
JH
Schiller
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000069347:Erlotinib Hydrochloride; D005076:Exanthema / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride
Erlotinib; NSCLC; Phase II