Activity and safety of erlotinib as second- and third-line treatment in elderly patients with advanced non-small cell lung cancer: a phase II trial

Abstract

Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Efficacy of this drug was documented in the BR.21 trial showing that adenocarcinoma, female gender, Asian ethnicity and never-smoker status are predictive of clinical response to erlotinib. Retrospective studies documented the same benefits for elderly patients as young patients in terms of response, progression-free survival, and overall survival. The primary aim of our trial was to confirm these findings in a prospective way; the secondary aim was to identify if the aforementioned clinical characteristics may be predictive of response even in elderly patients. The trial included 31 patients with pretreated stage IIIB (2) and IV (29) non-small cell lung cancer (NSCLC). Median age was 75 years (range: 65-85). Twenty-seven patients were current/former-smokers and four never-smokers. Twenty-three patients are evaluable for response. Objective response rates were reported in five patients (16%). Five patients had stable disease (16%) and 13 progressive disease (43%). Seven patients had a "clinical benefit" from erlotinib (22.5%; 95% C.I.: 7.9-37.2%). Grade 3 skin rash was recorded in three patients (10%). Median survival was 9 months (range 1-30). Median time to progression was 3 months (range: 1-24 months). Our study confirmed erlotinib activity and safety as second- and third-line treatment in elderly patients with advanced NSCLC, especially in terms of median survival. Even though this trial does not allow us to draw a definitive conclusion about the role of a particular clinical characteristic predictive of response, the "clinical benefit" was documented especially in females, in patients with adenocarcinoma histology and skin rash, confirming previous retrospective data.

Gemcitabine Plus Vinorelbine as the Second-Line Treatment and Beyond in Elderly Patients with Platinum-Pretreated Advanced Non-Small Cell Lung Cancer

“…This study showed a DCR of 65% and 9.5-month median OS in the elderly group, and there was no significant difference in outcome and toxicity between elderly and younger patients [8]. An EGFR TKI such as erlotinib and gefitinib also showed an improved survival and a favorable response rate [3,10]. In the present study, GV combination chemotherapy was not inferior to the salvage regimens described above in elderly patients, and all patients were previously treated with taxane, pemetrexed or EGFR TKI, as previously mentioned.…”

“…In those patients, salvage therapy has been shown to improve survival compared with the best supportive care alone [6,7]. Although the majority of patients enrolled in a salvage trial were younger, several data for salvage treatment have been reported in elderly patients [3,8,9,10,11]. These studies demonstrated that there were no differences in the efficacy of salvage chemotherapy between elderly and nonelderly patients, and old age itself should not be a contraindication for salvage chemotherapy [3].…”

“…These studies demonstrated that there were no differences in the efficacy of salvage chemotherapy between elderly and nonelderly patients, and old age itself should not be a contraindication for salvage chemotherapy [3]. However, previous studies for salvage regimens in elderly patients were limited to only a few agents, such as docetaxel, pemetrexed and targeted agents [3,8,9,10,11], all of which have some disadvantages. Docetaxel shows considerable toxicity and the efficacy of pemetrexed or targeted agents is limited to selected patients with an appropriate histology or molecular target.…”

Erlotinib as second- or third-line treatment in elderly patients with advanced non-small cell lung cancer: Keio Lung Oncology Group Study 001 (KLOG001)

“…Patient characteristics (all, <75 years and ≥75 years of age). ≥65 years) Italian patients with advanced NSCLC (n=31), the ORR was 16% (6). We hypothesized that the higher ORR in our study reflects the inclusion of a higher proportion of patients with EGFR mutation-positive tumors.…”

“…Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is an effective standard second-line treatment for NSCLC, regardless of EGFR mutation status (4)(5)(6)(7)(8). In a previous phase III study (BR.21), erlotinib prolonged overall survival (OS) and progression-free survival (PFS) compared with placebo when used as secondor third-line treatment of NSCLC; the OS was 6.7 and 4.7 months [hazard ratio (HR)= 0.61; P<0.001) and the PFS was 2.2 and 1.8 months (HR= 0.70; P<0.001) in the erlotinib and placebo groups, respectively (4).…”