# Triple-positive non-small cell lung cancer harboring EGFR mutation, ALK rearrangement, and high PD-L1 expression: a case report and literature review

## TL;DR

A rare lung cancer case with EGFR mutation, ALK rearrangement, and high PD-L1 shows that combined therapies and molecular profiling can lead to effective treatment.

## Contribution

Presents a rare triple-positive NSCLC case and highlights the importance of dynamic molecular profiling for treatment adaptation.

## Key findings

- Initial treatment with osimertinib and chemotherapy provided 17 months of disease control.
- NGS at progression revealed ERBB2 amplification, leading to a switch to alectinib with tumor regression.
- Sequential targeted therapy guided by NGS is critical for managing this complex cancer subtype.

## Abstract

Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are typically considered mutually exclusive in non-small cell lung cancer (NSCLC). However, rare cases with coexisting EGFR/ALK alterations and high programmed death ligand-1 (PD-L1) expression, termed “triple-positive” NSCLC, have been reported. Optimal treatment strategies for this unique subgroup remain undefined.

We describe a 54-year-old woman with stage IV lung adenocarcinoma harboring an EGFR exon 19 deletion, ALK–EML4/KIF5B fusion (V3a/b), and high PD-L1 expression (TPS = 90%). The patient received first-line osimertinib combined with pemetrexed/cisplatin, achieving durable disease control for 17 months. Upon progression, rebiopsy and next-generation sequencing (NGS) revealed persistent ALK fusion and newly acquired ERBB2 amplification. Treatment was switched to alectinib, leading to significant tumor regression and partial response.

This case illustrates that in triple-positive NSCLC, initial EGFR-TKI combined with chemotherapy can achieve long-term control, while dynamic molecular profiling at progression is essential for identifying resistance mechanisms. Sequential targeted therapy guided by NGS remains a cornerstone for precision management in this complex molecular subtype.