Determinants of tumor response and survival with erlotinib in patients with non--small-cell lung cancer.
OBJECTIVE
Erlotinib is a highly specific epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. This phase II study of erlotinib in patients with HER1/EGFR-expressing non-small-cell lung cancer previously treated with platinum-based chemotherapy evaluated tumor response, survival, and symptom improvement.


METHODS
Fifty-seven patients received an oral, continuous daily dose of 150 mg of erlotinib. Assessments of objective response used WHO and Response Evaluation Criteria in Solid Tumors criteria. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, supplemented with a lung cancer module, Quality of Life Questionnaire LC13, was used to measure health-related quality of life. Additional analyses were performed to identify predictors of response and survival.


RESULTS
The objective response rate was 12.3% (95% CI, 5.1% to 23.7%). Responses were observed regardless of type or number of prior chemotherapy regimens. Median survival time was 8.4 months (95% CI, 4.8 to 13.9 months), and the 1-year survival rate was 40% (95% CI, 28% to 54%). Erlotinib therapy was associated with tumor-related symptom improvement. The drug was well tolerated; drug-related cutaneous rash and diarrhea were observed in 75% and 56% of patients, respectively. One patient experienced toxicity consisting of severe grade 3 rash and diarrhea. Time since diagnosis and good performance status were significant predictors of survival in a multivariate Cox proportional hazards model, whereas HER1/EGFR staining intensity was not. Additionally, survival correlated with the occurrence and severity of rash.


CONCLUSIONS
Erlotinib was active and well tolerated in this patient population, and further clinical development is clearly warranted. Cutaneous rash seems to be a surrogate marker of clinical benefit, but this finding should be confirmed in ongoing and future studies.
Department of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 E 210th St, Bronx, NY 10467, USA. rperezso@montefiore.org
Román
R
Pérez-Soler
Abraham
A
Chachoua
Lisa A
LA
Hammond
Eric K
EK
Rowinsky
Mark
M
Huberman
Daniel
D
Karp
James
J
Rigas
Gary M
GM
Clark
Pedro
P
Santabárbara
Philip
P
Bonomi
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016019:Survival Analysis; D016896:Treatment Outcome
D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors