A Study On The Long Term Survivors In An Expand Access Program (EAP) Of Gefitinib In China EGFR Gene Mutations In Advanced Non-small Cell Lung Cancer And Its Influence On Effect Of Gefitinib

Gefitinib is a kind of EGFR Tyrosine Kinase Inhibitor (TKI) and demonstrated same efficacy in survival and better safety profile compared with standard chemotherapy for pre-treated NSCLC patients. Active mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib.The Expand Access Program of Iressa was initiated in2001in China with the objective to provide gefitinib to patients with NSCLC who had failed to standard treatment, or patients who could not tolerate chemotherapy, or patients who were ineligibile for other clinical trials with gefitinib. It is clinically interesting to describe the QoL, tumour control status, safety and clinical/genomic feature of the long-term survivors in the EARThe primary objective is to describe the quality of life of long-term survivors who are not terminated from the EAP. Secondary objectives is to determine the clinical characteristics of long-term survivors in the EAP program. This was a descriptive observational study. A total of934patients were screened in EAP database.25of them were active long-term survivors and34of them were long-term survivors terminated from EAP. The data of875fast-progressers were extracted from the existing EAP database.ESULTSThe mean FACT-L Score was62.88, the mean TOI score was36.46and the mean LCS score was12.79. In PWB, for question "I have a lack of energy",70.8%patients felt no lack of energy, and20.8%patients felt a little bit lack of energy. In FWB, for question "I am able to enjoy life",50.0%patients were able to enjoy life very much, and29.2%patients were able to enjoy life quite a bit. For question "I am content with the quality of my life right now",62.5%patients were content with the quality of their life very much, and12.5%patients were content with the quality of their life quite a bit. PS0-1accounted for91.66%when they were evaluated in the cross-sectional survey. Age<65years (68.52%), adenocarcinoma(81.36%), female(55.39%) and never-smoker(70.69%) accounted for the majority of long-term survivors. For those long-term survivors, the objective response rate (CR+PR) was37.5%, the disease control rate(CR+PR+SD) was87.5%and the median duration of response time was almost68months, which demonstrated good efficacy of gefitinib. The percentage of female was higher in long-term survivor group compared with fast-progressers,(55.93%vs40.81%, P=0.0227).CONCLUSIONGefitinib250mg offers a good QoL and efficacy for those long-term survivors even after more than3years treatment. Gefitinib has shown good tolerability for long-term survivors treated with gefitinib in this study. For EGFR mutation in this study, the results are only descriptive and no conclusion can be drawn because of the limitation of sample size. The possible explanation for the low EGFR mutation rate in the long-term survivors could be that EGFR mutation-carrying tumour cells have been killed or well controlled so that no or little EGFR mutation carrying tumour cells left in the tissue sample and no or little mutant DNA fragments were released to blood. Further analyses on paired tumour samples (before and after TKI treatment) from long-term survivors are needed to address this hypothesis. Objective This paper reports distribution of EGFR gene mutations in advanced non-small cell lung cancer (NSCLC) and its influence on effect of gefitinib. Method From Jan2007to Dec.2009,160patients with advanced non-squamous NSCLC received EGFR mutation test, and The EGFR exon19and21were amplified by mutant-enriched nested PCR and analyzed by direct sequencing. Among those patients,111received gefitinib therapy. Overall survival (OS) and progress-free survival(PFS) were calculated using the Kaplan-Meier method and a COX regression analysis was used to detect differences between strata. Results The percentage of EGFR mutation in advanced non-squamous NSCLC was55%, and it was only significantly related with pathological type. OS of patients with or without EGFR gene mutaions were29.0months (95%confidential interval (CI)24.2～33.8) and21.0months (95%Cl14.7～27.3) repectively, and the difference was not significant. PFS of patients with or without EGFR gene mutaions were17.0months (95%CI5.6～17.6) and11.6months (95%CI8.6～25.4), and the difference was significant (p=0.022). OS was significantly related with ECOG status and pathological type, and PFS significantly related to ECOG status, former regimens number and EGFR mutation status. There were no significant difference in OS and PFS between patients with EGFR exon19deletion mutation and those with exon21point mutation. Conclusion PFS of patients with EGFR mutation was better than those without EGFR gene mutations, but OS was similar. There were no significant difference in OS and PFS between patients with EGFR exon19deletion mutation and those with exon21point mutation.