Abstract 202P
Background
EGFR mutant NSCLC has shown remarkable response since the approval of osimertinib in the first-line. However, despite initial response, many patients do not show sustained clinical benefit. This is attributed to other intrinsic mechanisms owing to concurrently occurring genomic alterations along with EGFR, both clonal and/or subclonal. This is one of the largest cohorts depicting the effect of these mutations on TKI treatment.
Methods
192 patients of advanced EGFR mutant NSCLC treated with first-line EGFR TKI were included. Next generation sequencing was performed on the diagnostic tumor blocks using a customized lung panel comprising 34 genes. Clinical and genomic features were correlated with outcomes like PFS, OS and objective response rates.
Results
Of the 192 patients included, at least 1 additional genomic alteration was encountered in 91 cases (47.6%). Median number of additional mutations was 2 per patient. EGFR exon 19 mutations were more commonly associated with concurrent alterations when compared to the L858R group (68.6% vs 41.1%, p = 0.05). Uncommon EGFR subgroup showed no additional alterations. Most frequent co-mutation was in the TP53 gene seen in 91 (47.5%) cases, followed by PI3KCA in 41 (21.4%) cases. Other alterations seen included PTEN (9.8%), RB1 (7.2%), KRAS (6.9%), KDR (3.2%) mutations, and FGFR1 and MET amplification. Exon 19 subgroup showed a higher occurrence of PTEN and RB1, contrary to L858R which showed higher TP53 and PIK3CA alterations. Patients with co-occurring PIK3CA showed a shorter PFS (7.8 months vs. 11.3 months p < 0.05) and OS (23.4 months vs. 34.3 months, p = 0.06) after adjustment for use of osimertinib. Similar trend was seen with TP53 concurrent mutations (HR for PFS: 1.78 95%CI = 0.9–2.1). There was no significant correlation of survival measures with the mutant allele burden or type of TKI used.
Conclusions
EGFR mutations in NSCLC show a higher prevalence in this part of the world, and this study also proves that the heterogeneity and molecular landscape of this molecular subgroup is distinct from that of the West. Impact on survival outcomes warrants panel based NGS testing at baseline in all EGFR mutant cases in order to optimise sequencing of TKIs.
Legal entity responsible for the study
U. Batra.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.