Targeted Therapy Moves to Earlier Stages of Non-Small-Cell Lung Cancer: Emerging Evidence, Controversies and Future Challenges

Abstract

Lung cancer continues to be the leading cause of cancer mortality and a serious health problem despite the numerous advances made in the last decade and the rapid advance of research in this field. In recent years, there has been a decrease in mortality from lung cancer coinciding with the approval times of targeted therapy. To date, targeted therapy has been used in the context of advanced disease in clinical practice, with great benefits in survival and quality of life. The next step will be to incorporate targeted therapy into the treatment of earlier stages of non-small-cell lung cancer, and there is already a randomized trial showing a disease-free survival benefit. However, there are many questions that need to be resolved first. In the present review, the authors discuss the findings of published reports and ongoing clinical trials assessing the role of targeted therapies in nonmetastatic disease.

Tweetable abstract

The time has come to offer targeted therapy to patients with earlier-stage non-small-cell lung cancer, which could represent an important qualitative leap in the treatment of lung cancer patients. Review of evidence and discussion.

Lay abstract

Despite major therapeutic advances over the last decade, lung cancer continues to present the highest mortality rate of all cancers. Precision and personalized therapy directed at specific alterations in the genetic material of the tumor as well as immunotherapy has significantly improved survival in metastatic non-small-cell lung cancer. The next step will be to incorporate precision medicine into the treatment of earlier stages of non-small-cell lung cancer. The recent publication of the results of the ADAURA phase III trial showing a significant improvement in disease-free survival in patients with resected EGFR-mutated non-small-cell lung cancer who received an adjuvant EGFR-directed tyrosine kinase inhibitor called osimertinib has opened the doors to the incorporation of this novel agent into routine clinical practice. However, there are many questions that need to be resolved first. In the present review, the authors discuss the findings of published reports and ongoing clinical trials assessing the role of precision medicine in nonmetastatic disease.

Keywords::

• adjuvant
• afatinib
• alectinib
• ALK
• crizotinib
• early-stage
• EGFR
• erlotinib
• gefitinib
• localized NSCLC
• neoadjuvant
• non-small-cell lung cancer
• NSCLC
• oncogenic driver
• osimertinib
• ROS1
• targeted therapy

Author contributions

X Mielgo-Rubio coordinated the review and contributed to the writing of the manuscript and the review process. V Calvo wrote the sections of the manuscript related to adjuvant and neoadjuvant strategies with immunotherapy. J Luna and M Martín wrote the sections of the manuscript related to radiotherapy. J Remon wrote the sections of the manuscript related to unresectable locally advanced non-small-cell lung cancer. J R Jarabo wrote the sections of the manuscript related to thoracic surgery. O Higuera wrote the sections of the manuscript related to biomarkers. E Conde and F López-Ríos wrote the sections of the manuscript related to the rationale for personalized treatment in early-stage non-small-cell lung cancer. J De Castro, M Provencio and F H Trancho reviewed the manuscript and provided feedback. F Couñago coordinated the project and reviewed the manuscript.

Financial & competing interests disclosure

X Mielgo-Rubio has an advisory role with Boehringer Ingelheim, AstraZeneca and Bristol Myers Squibb; is a member of the speakers bureau for Roche, AstraZeneca, Bristol Myers Squibb, MSD and Abbott; and receives other research funding from Bristol Myers Squibb. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

X Mielgo-Rubio has an advisory role with Boehringer Ingelheim, AstraZeneca and Bristol Myers Squibb; is a member of the speakers bureau for Roche, AstraZeneca, Bristol Myers Squibb, MSD and Abbott; and receives other research funding from Bristol Myers Squibb. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed