The treatment of NSCLC has changed drastically in the last decade since the discovery of biomarkers like EGFR, ALK, ROS etc. Most common EGFR mutations in NSCLC include del19 and exon 21 L858R mutations. However, approximately 10% of NSCLC patients have uncommon EGFR mutations (complex indels undetected by single gene testing, missense mutations involving G719, L861, & S768 codons, and exon 20 insertions) which do not respond as well to TKIs. Thus, it is very important to understand type of EGFR mutations in clinical practice. This retrospective study reviews prevalence of these mutations in an Indian NSCLC cohort along with the clinicopathologic characteristics.
A total of 470 EGFR mutated NSCLC were analyzed. Of these, cases harboring uncommon EGFR mutations (n=49), were reviewed retrospectively, for clinicopathologic features. This study was approved by ethics committee of the institute.
Of the 470 cases, 49 (10.42%) were found to have uncommon EGFR mutations. The median age was 66 years (35-87years). Almost equal sex predilection with 25 (51%) males and 24 (49%) females. Among these, 39 (79.6%) were never smokers, 7 (14.3%) smokers. Intrathoracic metastases in form of lung-lung spread were noted in 20 patients (40.8%); lung-pleura in 38 (77.6%) patients. Extrathoracic metastases noted include brain (n=18, 36.7%), liver (n=14, 28.6%), bone (n=25, 51%), &adrenals (n=4, 8.2%). Thirteen cases had dual mutations in EGFR including L861Q and G719X in 3 patients, G719X and S768I in 1 patient, L858R and S768I in 1 patient, del19 and L8585R in 1 patient and additional T790M with del 19 and L858R in 4 and 2 patients respectively. The mutation profile of patients with single mutations included 4 cases of L861, 5 cases of S768,8 cases of G719, 1 case of exon 18 insertion and 14 cases of exon 20 insertion. Patients with L861Q were males (p<0.047) and never smokers (p<0.018). Exon 20 insertions were more common in females (p<0.024). Nine patients received TKI treatment; Seven were treated with afatinib and two with osimertinib (one patient had T790M mutation, the other had S768I mutation).
Rare and dual EGFR mutations are a heterogeneous group with distinct clinical features. This study highlights the same in an Indian cohort of EGFR mutated NSCLC.
Ullas Batra.
Has not received any funding.
All authors have declared no conflicts of interest.