# Targeting the Uncommon: A Case Report of Osimertinib Response in Advanced NSCLC Patient with Dual EGFR (E701fs and L702fs) Frameshift Deletions

## TL;DR

A patient with rare EGFR gene changes in lung cancer responded well to osimertinib, suggesting the drug may work for uncommon mutations.

## Contribution

Demonstrates osimertinib's efficacy in a patient with dual EGFR frameshift deletions, expanding its potential use in rare mutations.

## Key findings

- The patient showed radiological and biochemical improvement within two months of osimertinib treatment.
- The response to osimertinib was durable, with continued stability at 11 months.
- This case supports considering osimertinib for uncommon EGFR mutations in advanced NSCLC.

## Abstract

Lung cancer is the leading cause of cancer death, and most cases are non-small cell lung cancer types. Some patients have changes in their cancer genes (alterations) that can be treated with special (targeted) medicines instead of conventional chemotherapy. We describe a patient with a very rare type of gene change (EGFR; epidermal growth factor receptor) who responded well to an oral pill known as osimertinib. This case shows that patients with even uncommon, rare gene changes may benefit from this medication.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers with adenocarcinoma being the most common subtype. Patients with stage IV NSCLC typically have poor prognosis. In these patients, identification of actionable genomic alterations allows for the selection of targeted therapy rather than chemotherapy or chemo-immunotherapy. EGFR mutations are a common oncogenic driver in NSCLC and are targetable by tyrosine kinase inhibitors (TKIs). However, most of the studies primarily focus on common mutations, which are exon 19 deletions (Ex19del) and exon 21 (L858R) point mutations, and there is inconsistent data on efficacy in the treatment of patients with uncommon EGFR mutations. Currently, the first-line treatment for patients with common EGFR mutations involves a third-generation TKI, typically osimertinib. This case describes a 66-year-old gentleman with two uncommon EGFR frameshift deletions (E701fs and L702fs). His tumor staging was denoted as cT3N2M1b, stage IVA. The patient demonstrated a radiological and biochemical response to osimertinib as part of the OCELOT clinical trial (supported by a grant from AstraZeneca), with evidence of tumor marker decline and radiographic improvement within two months of osimertinib treatment initiation. This response has been durable with continued radiological stability and biochemical improvement at 11 months and ongoing. This case will help guide management for patients with this uncommon EGFR mutations and contribute to the scarce literature of EGFR frameshift deletions in advanced NSCLC patients.