Vibhor Sharma, Kumar,prabhash, Vanita Noronha, Amit Joshi, Vijay Patil, Anuradha Choughule, Nilendu Purandare

Medical Oncology, Tata Memorial Centre, Mumbai

Objective:The primary end points of this study are: 1. Overall Survival in patients of NSCLC on gefitinib. The secondary end points of this study are: 2. Progression free survival in patients of NSCLC on gefitinib. 3. Toxicities of Gefitinib. 4. Factors affecting overall survival of patients receiving gefitinib. 5. Response Rate. Method: This study was conducted as a retrospective study in Medical Oncology Department in Tata Memorial Hospital, Mumbai. After getting Institutional Review Board approval, we did a systematic analysis of a prospectively maintained database of 319 patients of stage IV Non Small Cell Lung Cancer (NSCLC) who received Gefitinib in our hospital. Patient Inclusion Criteria 1) Age ≥ 18 years. 2) Patients diagnosed with stage IV Non Small Cell Lung Cancer (NSCLC). 3) Patients planned and administered gefitinib 4) ECOG Performance Status 0-3EGFR analysis was done in the Molecular laboratory in our hospital using Real Time PCR technique. Patient characteristics were summarized using descriptive statistics such as mean, median, or mode. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method and compared using the log-rank test, utilizing the SPSS® software (version 20.0; SPSS Inc., Chicago, IL, USA). Response rate to gefitinib was expressed in percentage. Factors affecting progression free survival, overall survival and gefitinib response rate were compared using univariate and multivariate logistic regression analysis. Result: out of 319 patients who received gefitinib, 1. 150 were males and 169 females. 2. 108 were EGFR mutation positive (exon 19:65; exon 21:34; exon 18:5; exon 20:1; nature not known: 3), 70 EGFR mutation negative, 141 EGFR mutation status not tested. 3. Age ranges from 25-82 yrs. Mean age: 56.8yrs Median age: 57yrs. 4. ECOG PS 1: 150; PS 2: 75; PS 3: 53 patients. 5. 64 smokers and 255 non smokers. 6. Adenocarcinoma 294; squamous cell carcinoma 11; others 14. 7. Gefitinib used as first line: 254; second line: 62; third line: 3. 8. Median progression free survival 6 months (std error 0.461). 9. On multivariate analysis, only response to gefitinib is associated with significantly longer progression free survival. 10. Median overall survival 13 months (std error 0.723). 11. On multivariate analysis, response to gefitinib, performance status and gefitinib induced skin toxicity are associated with significantly longer overall survival. 12. Response to gefitinib was analyzed in 311 patients. Disease Control Rate (DCR) and Objective Response Rate (ORR) was 64.6% and 29.2% respectively. DCR: Overall 64.6%; EGFR Mutation present 84.9%; EGFR Mutation absent 46.9%; EGFR Mutation not done 57.5%. ORR: Overall 29.2%; EGFR Mutation present 50.0%; EGFR Mutation absent 16.6%; EGFR Mutation not done 19.4%.13. On multivariate analysis, smoking status, EGFR mutation status and presence of gefitinib induced skin toxicity were the only factors affecting gefitinib response. 14. Gefitinib toxocities were assessable in 287 patients. 145(50.52%) patients had one or more toxicities. Grade3/4 toxicities were seen in 30(10.45%) patients. These were distributed as: dermatological 23 (8.01%), diarrhea 5 (1.74%), mucositis 2 (0.69%), fatigue 1 (0.34%), and vomiting 1(0.34%). 15. Gefitinib was interrupted due to toxicities in 24 (8.36%) patients. All patients wereable to resume gefitinib. In one patient, gefitinib was replaced by erlotinib due to recurrent grade 3 skin toxicity. Conclusion: We conclude that in EGFR mutant NSCLC, gefitinib is associated with a significantly longer Overall survival, Progression free survival and Response rates as compared to EGFR wild type. Gefitinib use is associated with tolerable toxicities, mostly dermatological and diarrhea. Toxicities of gefitinib are usually grade I/II, easily manageable and rarely require dose interruption.

Key Words: gefitinib  efficacy  non small cell lung cancer