The good news
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to zongertinib for the treatment of adult patients with metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) mutations. This is the first oral tyrosine kinase inhibitor (TKI) that has been approved for the initial treatment of HER2 mutated NSCLC.
Why it’s important
Alterations in the HER2 gene have been associated with the development and spread of cancer. HER2 mutations occur in about 2-4% of patients with NSCLC. Zongertinib is an oral TKI that specifically targets HER2. We highlighted this drug in a Science Made Simple less than a year ago. It was previously approved to treat HER2 mutated NSCLC after previous treatment with chemotherapy and is now approved for the first-line treatment of this disease. Zongertinib was evaluated in the Beamion LUNG-1 (NCT04886804) trial which included 72 untreated patients with advanced NSCLC with HER2 mutations. The response rate was 76% and nearly 50% of patients had control of their disease for 12 months or longer.
What it means for patients
Zongertinib represents a large step forward in the treatment of NSCLC patients with HER2 mutations with its approval as initial treatment. As with most TKI treatment options, there are potential side effects and precautions. The prescribing information includes warnings and precautions for liver and cardiac toxicity as well as interstitial lung disease/pneumonitis, and embryo-fetal toxicity. Since this is an accelerated FDA approval there will be more trials that will be performed to confirm the effectiveness of the drug.
What to look for
In the future, we could see the evaluation of zongertinib in combination with other agents such as chemotherapy. It is also important to remember that the drug is unlikely to be a cure for these patients and that there is still an urgent need to continue research efforts to determine why cancer cells are or become resistant to treatment. Expect that the development of novel drugs for this type of lung cancer will continue in the future.