HER2 Mutation: — Treatments with Antibody-Drug Conjugates

Exon 20 insertions are the most common HER2 mutation found in lung cancer. An exon is a section of the gene that carries instructions for making a protein. An insertion means a small extra sequence has been added to that section, which changes how the HER2 protein is built. This mutation type is the one that trastuzumab deruxtecan was studied in, according to NCCN evidence. Your molecular report will name the specific change found in your tumour, and your oncologist will confirm whether it is the type that the recommended treatment is designed to target.

Interstitial lung disease, or ILD, is inflammation or scarring in the lung tissue. It is one of the most important side effects associated with trastuzumab deruxtecan, and NCCN guidance flags it as a risk requiring active monitoring throughout treatment. Symptoms to report include new breathlessness, a dry cough that was not there before, or reduced ability to exert yourself. None of these should be assumed to be caused by the cancer itself during treatment. If you develop any of these symptoms, contact your oncology team the same day rather than waiting for your next scheduled appointment. ILD can appear weeks to months after starting treatment, so prompt reporting is essential.

Trastuzumab deruxtecan for HER2-mutant lung cancer has been studied in patients who had already received prior treatment, including chemotherapy and immunotherapy, and the NCCN recommendation reflects that context. Whether it is appropriate for you after prior treatment depends on your current fitness, how your disease responded earlier, and whether you have conditions that would raise the risk of serious side effects such as ILD. Your oncologist will weigh those factors before making a recommendation.

No — and this is a common source of confusion. In breast cancer, the most common HER2 finding is overexpression or gene amplification, not a mutation in the gene sequence. Earlier anti-HER2 drugs that work well in HER2-overexpressing breast cancer did not show the same activity in HER2-mutant lung cancer. Trastuzumab deruxtecan is used in both settings, but for different reasons that relate to the biology of each cancer type. Do not assume that a drug a family member received for HER2-positive breast cancer is the same as what your oncologist is recommending for HER2-mutant lung cancer.

Trastuzumab deruxtecan has received regulatory attention in India for certain cancer types, but availability, access pathways, and cost vary by centre and by individual situation. If your oncologist recommends it, they will advise on how to access it and what indicative costs to expect. Costs for newer oncology drugs can be substantial. If cost is a concern, raise it openly at your appointment rather than assuming it is out of reach — hospital oncology coordinators are often aware of patient assistance programmes or alternative access routes that are not widely advertised.

HER2 amplification means there are extra copies of the ERBB2 gene in the cancer cell, rather than a change in the gene sequence. In lung cancer, amplification is a different finding from mutation, and the evidence supporting targeted treatment is different and less settled than for mutation. NCCN guidance on HER2-amplified lung cancer continues to evolve. Your oncologist will advise on whether current evidence supports a targeted approach for your specific result, and this is a situation where a second opinion from a centre experienced in molecular lung cancer may be worthwhile.