Abstract
Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.
Highlights
Lung cancer is a leading cause of death in the world
In 2958 patients with lung adenocarcinoma having their specimens tested for epidermal growth factor receptor (EGFR) mutation, a total of 67 patients with lung adenocarcinoma harboring uncommon EGFR gene mutations, who had received an EGFR tyrosine kinase inhibitors (TKIs) treatment, were enrolled
EGFR TKIs had replaced platinum-based chemotherapy to be a standard therapy in patients of non-small cell lung cancer (NSCLC) harboring EGFR mutation, because many phase 3 randomized controlled trials demonstrated that patients receiving EGFR TKIs had better response rate and longer progression-free survival (PFS)
Summary
Lung cancer is a leading cause of death in the world. Platinum-based chemotherapy had been a standard therapy for metastatic lung cancer, but the treatment result is still limited and disappointing.In the past decade, non-small cell lung cancer (NSCLC) patients had been proved to have longer progression-free survival (PFS) and better response rate to epidermal growth factor receptor (EGFR)tyrosine kinase inhibitors (TKIs) if they a had sensitizing EGFR mutation in phase 3 clinical trials [1,2,3,4,5].EGFR TKIs had been the standard therapy in NSCLC patients with EGFR mutation. Platinum-based chemotherapy had been a standard therapy for metastatic lung cancer, but the treatment result is still limited and disappointing. Non-small cell lung cancer (NSCLC) patients had been proved to have longer progression-free survival (PFS) and better response rate to epidermal growth factor receptor (EGFR). Tyrosine kinase inhibitors (TKIs) if they a had sensitizing EGFR mutation in phase 3 clinical trials [1,2,3,4,5]. EGFR TKIs had been the standard therapy in NSCLC patients with EGFR mutation. Of all EGFR mutations in lung cancer, approximately 90% are common mutations, including in-frame deletions in exon 19 and an L858R point mutation in exon 21 [5,6,7]. Many uncommon mutations, called rare or non-classical mutations, were detected but the response to EGFR
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