1354P - Beyond the common mutation: Examining chemotherapy success in uncommon EGFR mutations

Background

Some prospective studies have shown that second-generation tyrosine kinase inhibitors (TKIs) provide better control in patients with non-small-cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations. However, studies comparing second-line chemotherapy efficacy between NSCLC patients with common and uncommon EGFR mutations remain rare. This retrospective study compared treatment outcomes in these patients.

Methods

Patients with EGFR-mutated advanced-stage NSCLC who received first-line EGFR-TKIs in a tertiary referral center were retrospectively reviewed between January 2010 and August 2022. Patients with a negative T790M test at disease progression who received second-line chemotherapy were enrolled. Progression-free (PFS)and overall (OS) survival were compared between advanced NSCLC patients with common and uncommon EGFR mutations using Kaplan–Meier and log-rank tests.

Results

Total 209 (54.8%) patients had a negative T790M mutation test and received second-line chemotherapy, of which 192 (92.3%) had a common EGFR mutation (exon 19 deletion or exon 21 L858R substitution), and 17 (8.2%) had an uncommon EGFR mutation. Patients in the common EGFR mutation group had significantly longer PFS than those in the uncommon EGFR mutation group (4.57 vs. 2.57 months, p = 0.031). While patients in the common EGFR mutation group had longer OS than those in the uncommon EGFR mutation group, the difference was nonsignificant (12.53 vs. 9.70 months, p = 0.501). A Cox proportional hazard regression analysis controlling for potential confounding factors indicated that an uncommon EGFR mutation was an independent prognostic factor for PFS(hazard ratio [HR] = 2.15, 95% confidence interval [CI]: 1.27–3.64).Being male was only the independent poor prognostic factor for OS (HR = 1.64, 95% CI: 1.22–2.21).

Conclusions

To our knowledge, this is the first study investigating the impact of EGFR mutation subtypes on second-line chemotherapy efficacy. This study suggests that patients with uncommon EGFR mutations have poorer chemotherapy responses and shorter survival than those with common EGFR mutations. The development of new treatment strategies for these patients remains an unmet need.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Science and Technology Council of Taiwan (NSTC 110-2314-B-006-098-MY3 and NSTC 111-2314-B-006-092-MY3.

Disclosure

All authors have declared no conflicts of interest.