Skip to main content

New Treatment Options for Stage IV NSCLC With Driver Alterations

*January 2023*

The ASCO Living Guideline for advanced non-small cell lung cancer (NSCLC) with driver alterations has gotten its first update, with data from recent studies — DESTINY-Lung01 and CodeBreaK100 — incorporated into the guidance.

In the update, published in the Journal of Clinical Oncology, Dwight H. Owen, MD, MS, of the Ohio State University in Columbus, and colleagues recommended that for pretreated patients with advanced NSCLC and an activating HER2 (ERBB2) mutation, moving on to monotherapy with trastuzumab deruxtecan (Enhertu) is an option, per DESTINY-Lung01 findings. And in previously treated patients with advanced NSCLC and a KRAS G12C mutation, monotherapy with sotorasib (Lumakras) is on the table based on CodeBreaK100 findings.

DESTINY-Lung01 results were presented at the 2021 European Society of Medical Oncology (ESMO) meeting, while CodeBreaK100 findings were shared at the 2022 American Association for Cancer Research (AACR) meeting. Multiple experts at the time offered their take on the value of the findings via VJ Oncology.

Alexander Spira, MD, PhD, of Virginia Cancer Specialists in Fairfax: I think the most important, practice-changing data [from ESMO21] was the new and updated data on trastuzumab deruxtecan. So this is an antibody drug conjugate [ADC], and we knew about this a long time ago. It’s an antibody against HER2. Previously, we saw that the drug had activity [in these patients] and that activity has borne out very nicely.

So we are seeing response rates — very significant response rates — in patients with HER2 mutations. Remember, it’s not HER2 amplification, it’s HER2 mutations. So it’s practice-changing — so please check for this mutation. You can’t put people on this drug unless you check for the mutation. It’s very important and we have to keep emphasizing that … It’s very exciting to have this data for 1-2% of lung cancer patients. There is a little bit of concern, however, because there is a real rate of drug-induced pneumonitis, higher than in the breast cancer population, and we need to keep that in mind, and recognize it early. Read more.