# The Evolving Interplay Between Targeted Therapy and Surgery for Resectable Lung Cancer

## TL;DR

This paper reviews how targeted therapies, when used with surgery, can improve outcomes for lung cancer patients with specific genetic mutations.

## Contribution

The paper highlights new clinical trial data showing targeted therapies can be used before or after surgery to improve survival and reduce recurrence.

## Key findings

- Adjuvant osimertinib improves disease-free and overall survival in EGFR-mutated lung cancer patients after surgery.
- Neoadjuvant osimertinib increases major pathologic response rates compared to chemotherapy in NSCLC patients.
- Adjuvant alectinib is effective for ALK-positive resectable NSCLC patients.

## Abstract

Lung cancer is one of the most common and deadly cancers worldwide. Surgery has been the main treatment for patients whose tumors can be removed, but many patients still experience recurrence after surgery. Novel medicines called targeted therapies can greatly improve outcomes for patients whose tumors have specific genetic changes. In this narrative review, we discuss landmark clinical trials of targeted therapies in resectable non-small cell lung cancer. We highlight how these therapies, when given before or after surgery, can lower the chances of cancer returning or improve survival. We also emphasize the importance of genetic testing to guide treatment planning. By bringing together the latest research, this review shows how targeted therapies are changing the treatment of resectable non-small cell lung cancer.

Background: Recent landmark clinical trials have introduced the role of targeted therapy with surgery for resectable non-small cell lung cancers (NSCLCs). Methods: This narrative review summarizes data from recent clinical trials and retrospective studies to highlight the evolving interplay between targeted therapy and resectable NSCLC. Results: For patients with epidermal growth factor receptor (EGFR) mutations, the ADAURA trial demonstrated significant improvements in disease-free and overall survival with adjuvant osimertinib after complete resection. The NeoADAURA trial expanded the role of osimertinib to neoadjuvant treatment as it showed benefit in major pathologic response rates when compared to chemotherapy alone. Neoadjuvant osimertinib may facilitate surgical resection, especially for patients with lymph node involvement. Furthermore, the ALINA trial established the role of adjuvant alectinib, another targeted therapy, for patients with anaplastic lymphoma kinase (ALK) positive resectable NSCLC. Given the evidence for use of these novel targeted therapies in patients with resectable lung cancer, early molecular profiling is critical for patients with NSCLC to help guide pre- and postoperative treatment. The use of targeted therapies may even expand to stage IV NSCLC as clinical trials are ongoing and could possibly redefine the role of surgery in advanced disease. Conclusions: While there are ongoing trials to clarify the optimal timing of targeted therapies and surgical resection, current data supports the use of targeted therapies as part of multimodality care in surgically resectable NSCLC.