Dr Nieva on the Role of ADCs in the NSCLC Treatment Paradigm

“It’s natural to try to find the best drugs to partner with TKIs in order to try to maximize those [improved] outcomes. Antibody-drug conjugates represent a new way of delivering chemotherapy with more pharmacokinetics [and] continuous exposure of the tumor cells to the drug, and there may be many advantages to doing that over free chemotherapy administration.”

Jorge Nieva, MD, an associate professor of clinical medicine at the Keck School of Medicine of the University of Southern California, discussed the effect antibody-drug conjugates (ADCs) have on the non–small cell lung cancer (NSCLC) treatment paradigm.

There are potentially more studies that will evaluate frontline ADCs for the treatment of patients with lung cancer who have actionable genomic alterations, Nieva began. He noted that data from the phase 3 FLAURA2 (NCT04035486) and MARIPOSA (NCT04487080) trials have demonstrated that an intensified regimen could lead to improved outcomes, particularly in patients with EGFR-mutated NSCLC. Determining the best drugs to pair with TKIs to maximize improved outcomes is natural, he added, especially as ADCs represent a new way of delivering chemotherapy with more pharmacokinetics than traditional delivery modalities and continuous exposure of the tumor cells to the drug, he emphasized. Furthermore, with TKIs alone, patients could eventually develop resistance, although cytoreductive strategies could help prolong time to resistance, whether it’s with chemotherapy, radiation therapy, or surgery, he contextualized. Additionally, for patients who choose to be more aggressive with their cancer treatment, it’s important to add cytoreductive agents, Nieva noted.

For example, updated data from FLAURA2 presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer revealed that osimertinib (Tagrisso) plus pemetrexed and carboplatin or cisplatin led to a statistically significant and clinically meaningful overall survival improvement compared with osimertinib monotherapy for the treatment of patients with EGFR-mutated advanced NSCLC.