Top advances of the year: Targeted therapy for lung cancer

• Published in: Cancer Vol. 130; no. 19; pp. 3239 - 3250
• Main Authors: Makarem, Maisam, Jänne, Pasi A.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-10-2024
• Subjects: Anaplastic Lymphoma Kinase - antagonists & inhibitors; Anaplastic Lymphoma Kinase - genetics; antibody‐drug conjugates; c-Met protein; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Central nervous system; Clinical trials; Disease resistance; Drug development; Drug resistance; Drug Resistance, Neoplasm - genetics; Effectiveness; ErbB-2 protein; genomic alterations; Health services; Humans; Kinases; Lung cancer; Lung diseases; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Molecular Targeted Therapy - methods; Non-small cell lung carcinoma; non‐small cell lung cancer; Oncogenes; Patients; Pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Reagents; Ret protein; Small cell lung carcinoma; Target acquisition; targeted therapy; Therapy; Tyrosine; tyrosine kinase inhibitors; tyrosine kinase inhibitors; targeted therapy; antibody‐drug conjugates; genomic alterations; non‐small cell lung cancer
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.35423

The past year has offered significant advancements in the field of non–small cell lung cancer (NSCLC), both in the early and advanced disease settings. The identification of guideline‐recommended actionable targets has provided the foundation for developing multiple new therapeutic agents. There has been a focus on developing drugs designed to overcome acquired resistance, a limitation of tyrosine kinase inhibitor–based therapy in lung cancer. In addition, there is an emerging trend toward combination therapies for patients in the first‐line setting with the goal of preventing or delaying resistance. Another promising area of development has been the use of antibody–drug conjugates, where there are the initial reports of central nervous system efficacy and activity in patients with genomic alterations. Over the past year, numerous publications and presentations have highlighted multiple therapeutic advances, offering new treatment options for patients with NSCLC. The focus of this review is to summarize the most impactful findings, emphasizing their significance in the evolving treatment landscape for NSCLC. Several landmark trials in lung cancer with practice‐changing clinical implications have been presented and published in 2023. This article reviews a selection of these trials as they relate to early and advanced‐stage oncogene‐driven lung cancer. The ADAURA and ALINA trials, in which targeted therapy given in the adjuvant setting has demonstrated improved clinical outcomes, are reviewed. In the advanced‐stage setting, recent trials in the context of specific oncogene drivers are reviewed, including EGFR, ALK, ROS1, RET, ERBB2 (HER2), BRAF, MET exon 14 skipping (METex14), and KRAS alterations. Also discussed are the results of several trials that have evaluated the use of combination therapies and resistance‐mechanism agnostic treatment strategies.
Plain Language Summary
Targeted therapy plays an important role for patients with early and advanced‐stage non–small cell lung cancer carrying specific genetic alterations.
New strategies that combine multiple therapies are now being studied in randomized clinical trials, with the goal of enhancing the effectiveness of targeted therapy for patients with advanced lung cancer.
Several clinical trials published this past year have contributed to significant advances in thoracic oncology. Here, the focus is on targeted therapy advances reported in 2023 that are impacting clinical decision‐making in everyday practice.