Dr Halmos on Treatment Sequencing in Relapsed/Refractory NSCLC

“We are looking forward to new trials which will hopefully offer better drugs in this domain.”

Balazs Halmos, MD, the director of the Multidisciplinary Thoracic Oncology Program and of the Section of Thoracic Medical Oncology at Montefiore Health Systems, as well as the director of Clinical Cancer Genetics and a professor of Clinical Medicine at the Albert Einstein College of Medicine, discussed treatment sequencing considerations in the second line and beyond for patients with non–small cell lung cancer (NSCLC).

Treatment options for patients in the second-line setting and beyond have historically been lacking, Halmos began. Investigators are working to develop effective agents with lesser toxicities than what are currently available, he continued. However, patients who are eligible for targeted therapies should consider these agents, he added.

Both fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) and telisotuzumab vedotin-tllv (Emrelis) are effective, FDA-approved options for patients with NSCLC who have experienced disease progression after prior therapy, Halmos stated. In May 2025, the FDA approved telisotuzumab vedotin for patients with pretreated locally advanced or metastatic, nonsquamous NSCLC with high c-MET protein overexpression. Data from the phase 2 LUMINOSITY trial (NCT03539536), which supported the approval, demonstrated that patients with high c-MET protein overexpression who received telisotuzumab vedotin (n = 84) experienced an overall response rate of 35% (95% CI, 24%-46%) and a median duration of response of 7.2 months (95% CI, 4.2-12).

T-DXd and telisotuzumab vedotin offer patients with relapsed/refractory disease the chance for better outcomes compared with standard-of-care treatments, Halmos noted. However, these drugs pose new challenges in terms of adverse effects (AEs), he said. For example, treatment with telisotuzumab vedotin can lead to neuropathy, which needs to be effectively monitored and managed, he added.

Patients who are not eligible to receive targeted agents will usually be treated with docetaxel, Halmos said. Investigators are looking forward to new clinical trials which will hopefully offer better treatment options for these patients, he concluded.