A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in the branch of Internal Medicine / Medical Oncology.
Johannesburg
1st September 2014 / Introduction: Tyrosine kinase inhibitors and EGFR mutations has changed the treatment approach to lung cancer globally. This retrospective study will look at factors associated with EGFR mutations and define the EGFR mutation rate in South Africa.
Methods: Retrospective record review from NSCLC patients in South Africa who were tested for EGFR mutations at Lancet Laboratories during 1st September 2009 to 30th June 2012. Chi-squared test was used to determine association with categorical variables. Kaplan- Meier survival analysis was done for OS and PFS between EGFR mutation positive and negative patients. Cox proportional hazards were used for subgroup analysis. Treatment practices and response were described.
Results: 170 lung cancer samples were evaluable for EGFR mutation and 37 were EGFR mutation positive (21.8%). There were 22 (59.5%) exon 19 deletions, 11 (29.7%) L858R mutations, two G719X mutations, one S768I mutation and one exon 20 insertion. The median age was 63 (range 27-85). There were more females (55.6%) than males (44.4%) sent for mutation testing. Most patients were whites (71%), followed by blacks (18.3%), and other race (10.7%). 85% of all NSCLC samples tested were adenocarcinoma. None of the squamous cell carcinoma tested was positive for EGFR mutation. Smoking status was inversely proportional to EGFR mutation status (p<0.001). Over 60% patients received chemotherapy first and second line and responses decreased with each line of chemotherapy. Median PFS and OS were not different between the EGFR mutation positive and negative groups (6.85 versus 6.8 months; HR 1.6; 95% CI 0.70-3.65; p=0.2543 and 11.5 versus 12.9 months; HR 0.70;
95% CI 0.28-1.75; p=0.44, respectively). On multivariate analysis, only non-white race was associated with decrease in OS (HR 6.66; 95% CI 2.31-19.19; p=0.0004).
Conclusion: EGFR mutation rate in South African lung cancer patients was 21.8%. 89% of all EGFR mutations were either exon 19 deletions or L858R point mutations. Most EGFR mutations were associated with adenocarcinoma of the lung in non-smokers. These findings were consistent with current literature in western countries. Treatment practice remained chemotherapy based, with few patients receiving EGFR TKIs. Efforts should be made to prioritized targeted treatment approach in lung cancer in South Africa.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/17432 |
| Date | 17 April 2015 |
| Creators | Chan, Sze Wai |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf, application/pdf |
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