The good news
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to sevabertinib for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) mutations and who have received prior systemic therapy. This is the most recent oral tyrosine kinase inhibitor (TKI) that has been approved.
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. In the past two decades, several clinical trials have investigated the use of anti-HER2 therapies in lung cancer but have led to disappointing results. Progress was made when in 2022, the FDA granted accelerated approval to trastuzumab deruxtecan for patients with unresectable or metastatic NSCLC whose tumors have HER2 mutations and who have received prior therapy. This drug is an antibody drug conjugate, which is a form of “targeted chemotherapy.” Thanks to continued research, zongertinib (another TKI) was approved earlier this year for previously treated HER2-mutated NSCLC — and now, sevabertinib is the third therapy approved for this rare subtype of NSCLC.
Sevabertinib is an oral TKI that specifically targets HER2 mutations. In the SOHO-01 (NCT05099172) clinical trial, 70 patients with locally advanced or metastatic NSCLC with HER2 (ERBB2) mutations who had received prior systemic therapy were treated with sevabertinib. An impressive 71% of the patients had significant shrinkage of their cancer and control of the cancer lasted over 9 months for many of the patients.
The most common side effect was diarrhea which was managed without the need to discontinue the drug. Other common toxicities included rash and nail changes. The prescribing information also contains warnings for potential liver toxicity, pneumonitis (lung inflammation), eye toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity.
What it means for patients
Sevabertinib represents another advancement in the treatment of NSCLC patients with HER2 mutations. Since this is an accelerated FDA approval, there will be more trials that will be performed to confirm the effectiveness of the drug. It is important that patients with advanced non-squamous NSCLC have their tumors tested for HER2 mutations.
What to look for
It is likely that sevabertinib will be evaluated as initial treatment for patients with HER2-mutated NSCLC in upcoming clinical trials with the hope that it will be more effective than chemotherapy as a first treatment. We could also see the evaluation of sevabertinib 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.
To learn more about HER2-mutant NSCLC, download this educational resource. If you have questions, you can connect with our Lung Cancer Support Line at (844) 835-4325 or email support@LCRF.org.
