The good news
The Food and Drug Administration (FDA) granted accelerated approval to datopotamab deruxtecan-dlnk for adults with locally advanced or metastatic epidermal growth factor receptor mutated (EGFRmut+) non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy.
Why it’s important
An antibody drug conjugate (ADC) is like a “guided missile.” It is composed of an antibody that binds to a “target” on the cancer cell. The ADC is then taken up by the cancer cell. Inside the cell a “linker” connecting the antibody to the chemotherapy (payload) is broken and the treatment is released. ADCs aim to deliver a concentrated dose of chemotherapy directly to cancer cells, minimizing damage to healthy cells. In the case of datopotamab deruxtecan (Dato-DXd) the target is TROP2. TROP2 is a glycoprotein that is present on the surface of many cells. It can be overexpressed in cancer cells thereby promoting cancer cell growth and survival. Two clinical trials, TROPION-Lung05 and TROPION-Lung01, contained a group of 114 patients with EGFRmut+ lung cancer who had received prior EGFR-directed therapy and platinum-based chemotherapy. These heavily pretreated patients received Dato-DXd. 45% of the patients experienced a significant shrinkage of their cancer. The treatment response often lasted more than 6 months. Side effects of special interest included soreness of the mouth (mucositis), changes on the surface of the eye, and inflammation of the lung (pneumonitis). Most side effects were low grade and there were no deaths related to treatment.
What it means for patients
Patients with advanced EGFRmut+ lung cancer benefit greatly from treatment that targets the EGFR mutation. Unfortunately, this highly effective therapy is not curative for the majority of patients. Inevitably these patients will get chemotherapy either initially or as subsequent treatment. Once therapy with the EGFR inhibitors and standard platinum-based chemotherapy are utilized the options for treatment are very limited. The ADC, Dato-DXd, represents a new alternative for these patients. The FDA approval is an “accelerated approval” which is a mechanism whereby drugs that are seen to have a clinical benefit are made available while awaiting more information from additional clinical trials. The drug company usually conducts more studies to confirm treatment benefit.
What to look for
Having an additional effective treatment option for patients with EGFRmut+ lung cancer who have exhausted other therapies is very important. However, more work needs to be done with the eventual goals of prolonging survival and even curing these patients. Look for more research and clinical trials employing novel agents in the treatment of EGFRmut+ lung cancer, developing more strategies to overcome resistance, and discovering biomarkers that determine which cancers are most likely to respond to treatment.