Erlotinib - high cost chemo may buy days to weeks of improved QOL in < 9% of patients with NSCLC

Erlotinib in advanced NSCLC has an 8.9% response rate with median duration of 7.9 months, and QOL scores showed improvement in cough(44%), dyspnea(34%), and pain (42%), compared to improved QOL scores in placebo of cough (27%), dyspnea (41%), and pain (28%), and these were statistically significant. The cost of Erlotinib 150 mg daily for 30 days is ~$3,150.00. patients with disease remission response were correlated with improved QOL scores. and other palliative measures were deemed responsible for the QOL and symptom improvement in the placebo arm.

Citation/s:
Bezjak A, Tu D, Seymour S, et al: Symptom Improvement in Lung Cancer Patients Treated With Erlotinib: Quality of Life Analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Onc;Aug 20, 2006;vol. 24;No. 24:3831-3836.
Lead author's name and fax: Andrea Bezjak, MD

Three-part Clinical Question: Among patients with advanced stage lung cancer, does erlotinib therapy alleviate symptoms and improve quality of life compared to traditional palliative medicine interventions.
Search Terms:

The Study:
Double-blinded concealed randomised controlled trial with intention-to-treat.
The Study Patients: Patients with stage IIIB or IV NSCLC with ECOG-PS 0-3, who had receiver one or two prior chemotherapy regimens and were not eligible for further chemotherapy. Survival was the primary study outcome. secondary outcomes were - progression-free survival, response rate, duration of response, toxicity, and Quality of Life. This article looks at the QOL endpoints.
Control group (N = 243; 227 analysed): Placebo-controlled. Control group received a placebo medication. There is no mention as to how the study was blinded.e.g. if the pills looked the same. Both arms were through 8 cycles (months) or until progression of disease or toxicity. Baseline and every 4 week QOL assessments were done while receiving treatment (placebo), then every 12 weeks for the duration of the study. Patients completed EORTC-QLQ C-30 and lung cancer specific LC-13 questionaires, looking at the following functional domains: Physical, emotional, role, cognitive, and social, with symptom domains of fatigue, nausea, vomiting, and pain, and single items: dyspnea, sleep appetite, constipation, diarrhea, and financial impact. the lung cancer module looks specifically at dyspnea, types of pain, cough, hemoptysis, dysphagia, stomatitis, alopecia and peripheral neuropathy. H & P, labs, and radiological evaluation as below.
Experimental group (N = 488; 457 analysed): Experimental group received 150mg erlotinib daily through 8 cycles or until progression of disease or toxicity, starting 2 days after randomization. Dose reduction to 100mg was instituted for severe rash or diarrahea. H & P, and labs done every 4 weeks along with QOL assessments as above, with radiologic evaluation every 8 weeks.

The Evidence:
Outcome Time to Outcome CER EER RRR ARR NNT
death 20 months 0.860 0.775 10% 0.085 12
95% Confidence Intervals: 3% to 17% 0.028 to 0.142 7 to 36
progression of disease 20 months 0.955 0.922 3% 0.033 30
95% Confidence Intervals: 0% to 7% -0.002 to 0.068 NNT = 15 to INF; NNH = 436 to INF

Non-Event Outcomes Time to outcome/s Control group Experimental group P-value
progression of cough 3.7 mo 4.9 mo .04
progression of dyspnea 2.9 mo 4.7 mo .03
progression of pain 1.9 mo 2.8 mo .04

Comments:
Does not clearly address our patient population (ECOG 3 = PPS 50%), and sub-analysis showed higher performance status and previous responders more likely to have benefit from erlotinib. So need to consider in very specific patients. But low NNT =12 with min. toxicity, low burden daily PO med informs the individual, case-by-case decision -making process. Very pricey medication compared with standard palliative interventions for symptom management.

Appraised by: Salli Whisman, MD ; Friday, January 12, 2007
Email: swhisman@hospicebg.org
Kill or Update By: 6/12/07