Best response rate by dose level.

<p>Best response rate by dose level.</p

Adverse events in all cycles of treatment for all patients receiving at least one cycle of treatment in the CSV and MSV groups.

<p>Adverse events in all cycles of treatment for all patients receiving at least one cycle of treatment in the CSV and MSV groups.</p

CONSORT Flow diagram.

<p>CONSORT Flow diagram.</p

Dose Escalation Schedule for the CSV and MSV arms.

<p>Dose Escalation Schedule for the CSV and MSV arms.</p

Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Using Two Different Schedules - Fig 3

<p>Mean plasma concentration-time curves of erlotinib (A) on Day 3 after initial oral dose with CSV dosing regimen of vinorelbine, (B) on Day 10 at the steady state after oral dose with CSV dosing regimen of vinorelbine, (C) on Day 3 after initial oral dose with MSV dosing regimen of vinorelbine and (D) on Day 10 at the steady state after oral dose with MSV dosing regimen of vinorelbine.</p

Patient demographics and baseline characteristics.

<p>Patient demographics and baseline characteristics.</p

Impact of Smoking and Brain Metastasis on Outcomes of Advanced <i>EGFR</i> Mutation Lung Adenocarcinoma Patients Treated with First Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

<div><p>Objectives</p><p>This purpose of this study was to examine clinical-pathologic factors – particularly smoking and brain metastases – in <i>EGFR</i> mutation positive (M+) lung adenocarcinoma (ADC) to determine their impact on survival in patients treated with first line EGFR TKI.</p><p>Methods</p><p>A retrospective review of <i>EGFR</i> mutation reflex testing experience for all ADC diagnosed at a tertiary Asian cancer centre from January 2009 to April 2013. Amongst this cohort, patients with advanced <i>EGFR</i> M+ ADC treated with first line EGFR TKI were identified to determine factors that influence progression free and overall survival.</p><p>Results</p><p>444/742 (59.8%) ADC reflex tested for <i>EGFR</i> mutations were <i>EGFR</i> M+. Amongst never-smokers (n=468), <i>EGFR</i> M+ were found in 74.5% of females and 76.3% of males, and amongst ever smokers (n=283), in 53.3% of females and 35.6% of males. Exon 20 mutations were found more commonly amongst heavy smokers (> 50 pack years and > 20 pack years, Pearson’s chi square p=0.044, and p=0.038 respectively). 211 patients treated with palliative first line TKI had a median PFS and OS of 9.2 and 19.6 months respectively. 26% of patients had brain metastasis at diagnosis. This was significantly detrimental to overall survival (HR 1.85, CI 1.09-3.16, p=0.024) on multivariate analysis. There was no evidence that smoking status had a significant impact on survival.</p><p>Conclusions</p><p>The high prevalence of <i>EGFR</i> M+ in our patient population warrants reflex testing regardless of gender and smoking status. Smoking status and dosage did not impact progression free or overall survival in patients treated with first line EGFR TKI. The presence of brain metastasis at diagnosis negatively impacts overall survival.</p></div

Univariate analysis of progression free survival and overall survival.

<p>Univariate analysis of progression free survival and overall survival.</p

Kaplan-Meier plots of cohort of 211 patients treated with 1^st line EGFR TKI; (a) PFS by brain metastasis in ECOG 0–1 patients, (b) PFS by brain metastasis in ECOG 2–4 patients, (c) OS by brain metastasis in ECOG 0–1 patients, and (d) OS by brain metastasis in ECOG 2–4 patients.

<p>Kaplan-Meier plots of cohort of 211 patients treated with 1^st line EGFR TKI; (a) PFS by brain metastasis in ECOG 0–1 patients, (b) PFS by brain metastasis in ECOG 2–4 patients, (c) OS by brain metastasis in ECOG 0–1 patients, and (d) OS by brain metastasis in ECOG 2–4 patients.</p

Sites of EGFR mutations amongst 461 patients.

<p>Sites of EGFR mutations amongst 461 patients.</p