Elsevier

Lung Cancer

Volume 66, Issue 2, November 2009, Pages 257-261
Lung Cancer

Clinical surrogate markers of survival in advanced non-small cell lung cancer (NSCLC) patients treated with second–third line erlotinib

https://doi.org/10.1016/j.lungcan.2009.01.014Get rights and content

Summary

Background

Inhibition of the EGFR pathway is a useful strategy in the treatment of patients with advanced NSCLC. The aim of this study is to assess predictive clinical parameters of efficacy.

Methods and patients

Sixty-two patients with advanced NSCLC were treated with erlotinib as second–third line (150 mg/day). Baseline patient characteristics were: performance status (PS) 1: 92%; median age, 58 years; males, 73%; adenocarcinoma, 45%; current/former smokers, 83%. During erlotinib treatment, 35% of patients had no rash, 32.3% had grade 1 rash, 26% had grade 2 rash and 6.5% patients developed grade 3 rash.

Results

For patients with grades 2–3 rash vs. those with grades 0–1 rash, time to tumor progression (TTP) and overall survival (OS) were 92 vs. 41 days (p = 0.0381) and 244 vs. 131 days (p = 0.011), respectively. For patients with non-smoking history and current/former smokers, TTP and OS were 136 vs. 42 days (p = 0.0015) and 324 vs. 133 days (p = 0.0242), respectively. In addition, rash grade and smoking history were found to have a highly significant impact on TTP and OS, according to the Cox model.

Conclusions

Grade ≥2 rash and non-smoking history are associated with improved TTP and OS in advanced NSCLC patients treated with erlotinib.

Introduction

Non-small cell lung cancer (NSCLC) is the leading cause of death cancer in the western world [1]. In metastatic disease chemotherapy (CT) prolongs survival and an overall median survival of 9–12 months can be reached. The epidermal growth factor receptor (EGFR) is a transmembrane receptor expressed at a high level in a variety of solid tumors, including NSCLC, and has been implicated in the control of cell survival, proliferation, metastases and angiogenesis [2]. Erlotinib is a potent reversible inhibitor of EGFR tyrosine-kinase domain that has been proven to prolong survival in NSCLC patients after failure of at least one prior CT regimen [3].

Knowing predictive markers of clinical benefit using EGFR tyrosine-kinase inhibitors is of great clinical relevance. Molecular markers, such as EGFR mutations and amplification or polisomy, have been correlated with higher response levels when EGFR tyrosine-kinase inhibitors are used [4], [5], [6], [7]. In retrospective studies using tyrosine-kinase inhibitors, clinical characteristics (adenocarcinomas, females, non-smokers and Asian ethnicity) have been associated with higher response rates [3], [4], [8], [9]. However, the role of clinical factors as predictors of a differential survival is in discussion. Furthermore in the recently published INTEREST study comparing gefitinib with docetaxel, these factors were associated with longer survival in both group of treatment [10]. Rash is the most frequent adverse event of patients treated with anti-EGFR agents and some retrospective studies have found a correlation between rash and survival [3], [9], [11], [12], [13]. Thus, the aim of this study is to evaluate potential clinical predictor factors of time to tumor progression (TTP) and overall survival (OS) in advanced NSCLC patients treated with erlotinib.

Section snippets

Study design

We analyzed data from 62 patients included in a phase II pharmacodynamic study which evaluated the effect of erlotinib on patients with NSCLC after CT failure [14]. Eligibility criteria were histologically/cytologically confirmed advanced NSCLC, disease progression after ≥1 platinum-based chemotherapy regimen; tumor biopsy; age >18 years; performance status (PS) 0–1; life expectancy of ≥12 weeks; ≥14 days (radiotherapy) or 28 days (chemotherapy) since last treatment; adequate bone marrow,

Results

Characteristics of the patient population included in this study are outlined in Table 1. All 62 patients were evaluable for response and survival. Partial responses were noted in 6 patients (9.6%) and stable disease in 16 patients (26%). Median follow-up for all patients was 123.5 days (range, 15–610 days). The median TTP was 43 days (95% CI 19–326 days) and OS was123.5 days (95% CI 15–610 days).

Most of the patients (65%) presented some degree of rash. The distribution of skin rash was: grade

Discussion

Clinical and molecular parameters have been identified as possible predictors of clinical benefit to tyrosine-kinase inhibitors in patients with advanced NSCLC [11], [15].

Women, adenocarcinoma, Asian ethnicity and never smokers presented better outcomes in some reports, but most recent studies suggests these factors as prognostic but not all as predictors of response [3], [10], [13].

In our study only never smokers and patients with skin rash were associated with higher TTP and OS. Gender was

Conflict of interest statement

Author's have no conflict of interest.

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