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New study using real-world UK data supports the use of HER2-directed therapies for HER2-positive salivary gland cancers

By Katherine O'Connor Share this article

HER2-directed therapies

RESEARCH SPOTLIGHT: New study using real-world UK data supports the use of HER2-directed therapies for HER2-positive salivary gland cancers

Salivary Gland Cancer (SGC) is a rare malignancy, accounting for about 5% of all head and neck cancers. It can also present in other areas of the body, including the windpipe, breast, skin and the vulva. While surgery followed by radiotherapy is the standard treatment, alternative therapies that target specific cancer mechanisms are showing promise.

One approach targets Human Epidermal Growth Factor Receptors (HERs), proteins on the cell surface that play a crucial role in cell growth and survival. There are four types of HERs, and when certain molecules bind to them, it causes them to join together and form a pair. This initiates signalling pathways, triggering the activity of enzymes and leading to cell growth, cell proliferation and blood vessel development—key processes in cancer development [1].

HER2 is the favoured partner of choice when HER pairs form, so most have one, or two, HER2 proteins. Normal cells contain few HER2 molecules, so pairs rarely form and growth signals are weak. When HER2 is overexpressed, more pairs form, more signalling occurs and cancers can develop [2]. While most studies on HER2 focus on breast cancers [3], it impacts the development of other cancers [4-6], including SGC [7,8]. It is reported to play a role in up to 13% of adenocarcinomas, not otherwise specified (NOS) and 43% of salivary duct carcinomas [9].

Therapies that target HER2 can reduce the formation of HER pairs and so reduce the subsequent processes that cause cancer. The main available options are based on a drug called trastuzumab. Clinical trials have shown that HER2-directed therapies can be effective in treating SGC [10]. One trial looked at ten cancer patients receiving ado-trastuzumab emtansine (also called TDM1), and observed a high response rate of 90%. Five of these patients had a complete response (i.e. the disappearance of all signs of cancer) [11]. Another trial looked at 57 patients receiving a combination of trastuzumab and the chemotherapy drug docetaxel, and also observed a high response rate of 70.2% [12].

While these data are encouraging, the sample sizes are small and evidence of efficacy outside of clinical trials is lacking. The treatment is therefore not approved for routine use to treat SGC in the UK. Gaining a better understanding of real-world use (i.e. outside of clinical trials), including the expected duration and choice of treatment, is crucial to informing its routine use.

A new study by Haigh et al (2024) [13] sought to address this by describing the outcomes of 18 real-world cases of HER2-directed therapy use within the UK NHS.

Key findings:

  • The choice of HER2-directed therapy varied, with ado-trastuzumab emtansine (TMD1) being the most common.
  • 13% of patients had durable responses to treatment (i.e. responses lasting more than 12 months), indicating the potential for long-term efficacy.
  • The median treatment duration was 8.3 months.
  • One responder experienced a complete response after 47 months, demonstrating the potential for the therapy to eliminate cancer.
  • The therapies were well-tolerated, with only one patient discontinuing treatment due to negative side effects.

While the sample size is limited (a common limitation due to the rarity of SGC), it is the largest dataset of its type and shows that the outcomes of real-world use of HER2-directed therapies are similar to those reported in clinical trials. This is an important next step in understanding the treatment and demonstrates that it can be effective in controlling, and even eliminating, cancer in real-world scenarios. This information can inform clinical and wider healthcare system decision-making, and highlights the importance of screening SGC patients for HER2 activity so that these alternative treatment options can be explored when traditional therapies fall short.

Salivary Gland Cancer UK is here to support those affected by, treating and researching rare Salivary Gland Cancers. Whether you're a patient, the caregiver for a patient, a family member or a friend, we are here to support you. We provide peer support and reliable information for those affected by all the Salivary Gland Cancers. Join the SGC UK network, and we’ll keep you up-to-date via email with all the latest events and news.

 

References

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  2. Iqbal, N. and Iqbal, N., 2014. Human epidermal growth factor receptor 2 (HER2) in cancers: overexpression and therapeutic implications. Molecular biology international, 2014(1), p.852748.
  3. Krishnamurti, U. and Silverman, J.F., 2014. HER2 in breast cancer: a review and update. Advances in anatomic pathology, 21(2), pp.100-107.
  4. Albarello, L., Pecciarini, L. and Doglioni, C., 2011. HER2 testing in gastric cancer. Advances in anatomic pathology, 18(1), pp.53-59.
  5. Hellström, I., Goodman, G., Pullman, J., Yang, Y. and Hellström, K.E., 2001. Overexpression of HER-2 in ovarian carcinomas. Cancer research, 61(6), pp.2420-2423.
  6. SiShi, L., Buchbinder, E., Wu, L., Bjorge, J.D., Fujita, D.J. and Zhu, S., 2014. EGFR and HER2 levels are frequently elevated in colon cancer cells. Discoveries Reports, 1(1), p.e1.
  7. Can, N.T., Lingen, M.W., Mashek, H., McElherne, J., Briese, R., Fitzpatrick, C., van Zante, A. and Cipriani, N.A., 2018. Expression of hormone receptors and HER-2 in benign and malignant salivary gland tumors. Head and neck pathology, 12, pp.95-104.
  8. Skálová, A., Starek, I., Vanecek, T., Kucerová, V., Plank, L., Szépe, P., Di Palma, S. and Leivo, I., 2003. Expression of HER‐2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in‐situ hybridization and immunohistochemistry. Histopathology, 42(4), pp.348-356.
  9. Egebjerg, K., Harwood, C.D., Woller, N.C., Kristensen, C.A. and Mau-Sørensen, M., 2021. HER2 positivity in histological subtypes of salivary gland carcinoma: a systematic review and meta-analysis. Frontiers in Oncology, 11, p.693394.
  10. Filippini, D.M., Pagani, R., Tober, N., Lorini, L., Riefolo, M., Molinari, G., Burato, A., Alfieri, S., Bossi, P. and Presutti, L., 2024. HER2-targeted therapies for salivary gland cancers. Oral Oncology, 148, p.106612.
  11. Li, B.T., Shen, R., Offin, M., Buonocore, D.J., Myers, M.L., Venkatesh, A., Razavi, P., Ginsberg, M.S., Ulaner, G.A., Solit, D.B. and Hyman, D.M., 2019. Ado-trastuzumab emtansine in patients with HER2 amplified salivary gland cancers (SGCs): Results from a phase II basket trial.
  12. Takahashi, H., Tada, Y., Saotome, T., Akazawa, K., Ojiri, H., Fushimi, C., Masubuchi, T., Matsuki, T., Tani, K., Osamura, R.Y. and Hirai, H., 2019. Phase II trial of trastuzumab and docetaxel in patients with human epidermal growth factor receptor 2–positive salivary duct carcinoma. Journal of Clinical Oncology, 37(2), pp.125-134.
  13. Haigh, J.E., Patel, K., Rack, S., Jiménez-Labaig, P., Betts, G., Harrington, K.J. and Metcalf, R., 2024. The Clinical Utilisation and Duration of Treatment with HER2-Directed Therapies in HER2-Positive Recurrent or Metastatic Salivary Gland Cancers. Current Oncology, 31(9), pp.5652-5661.