Incidence and treatment outcome of EGFR and inactivating P53 alterations in a cohort of 218 consecutively tested patients from a certified lung cancer center
Introduction: p53 mutations are common in lung cancer, and have also been described in EGFR mutated patients. The impact of p53 mutations in EGFR mt patients is controversial, current data suggest that p53 mutations do not represent a negative prognostic marker and also are not a negative predictive factor for response to EGFR TKI. The aim of the study was therefore to systematically analyze EGFR and p53 mutations within a cohort of patients with lung cancer stage IV (UICC 7), to correlate alterations with clinical characteristics and to investigate a potential impact of p53 mutation status on treatment outcome.
Methods: 218 patients from a single center diagnosed with lung cancer stage IV were studied for the presence of EGFR as well as inactivating p53 mutations. Methods for the detection of EGFR mutations included Sanger Sequencing and hybridization based COBAS testing. P53 mutations were detected by Sanger Sequencing. Clinical characteristics including smoking status were available for all patients.
Results: 218 consecutive patients at the lung cancer center of the Pius-Hospital Oldenburg were studied. The overall EGFR mutation rate was 21% (45/218) in all patients, 80% (36/45) showing common mutation of exon 19 or 21. P53 WT was found in 47% (17/36) whereas p53mt showed in 36% (13/36), in 6/36 patients P53 analysis was not successful. OS was 30 months in p53mt patients, median of OS was not yet reached in p53 WT patients. PFS on 1st line TKI therapy was 11 months in p53mt patients and 20 months in p53 WT. These differences were almost statistically significant.
Conclusion: There was a numerical difference in the PFS in p53mt vs. WT patients with EGFR mutations on TKI. These differences were not statistically significant, most likely due to the limited number of patients. Also there was a numerical difference in OS in the two subgroups, however these differences were not statistically significant. These data have to be expanded to a larger cohort of patients.