BCAC’s Louise Malone was among 10,000 attendees at this premier international breast cancer research conference held in Texas, 3-8 December. She shares some of the key themes she observed among the many workshops, posters and sessions.
“De-escalation” of therapies
Doing less, while still achieving good results, continues to be the driver behind much of the research in surgery and radiation therapy, with less invasive and time-consuming procedures being investigated. This trend is less evident in medical oncology, although there is a growing awareness that, with success in extending the lives of patients with breast cancer there is also now a need to reduce the toxicity of long-term side effects of treatments that can severely affect quality of life.
The FDA (USA’s medicines regulator) is now encouraging those developing new cancer medicines to put more effort into getting the dosages used in the earliest clinical trials just right. Traditionally, new cancer medicines being tested in Phase 1 trials are given at the ‘highest tolerable dose’, i.e enough to ensure the maximum number of cancer cells will be killed without also killing the patient. If the medicine passes Phase 1, then those high initial doses can become the standard on which the more extensive (and expensive) Phase 2 and 3 trials are based. It’s very difficult once that standard has been set to go back and try lower dosages. This method works fine when no-one expects much extension of life, but it’s not so appropriate now that a person with advanced disease might expect to have years of taking a succession of breast cancer medicines. If doses could be reduced so that the medicines still work, but unpleasant side effects like nausea, diarrhea, rashes, mouth ulcers, alopecia, neutropenia and interstitial lung disease are minimised then that would be of great benefit to many.
New targeted therapies – ADCs
Antibody-drug conjugates (ADCs) continue to be a rich source of new medicines for advanced breast cancer, and potentially for early breast cancer too. Datopotamab deruxtecan is a new ADC showing great promise for HR+/HER2- advanced breast cancer. Further results from long-term trials with sacituzumab govitecan (Trodelvy) and trastuzumab deruxtecan (Enhertu) continued to show the benefits of these medicines for several subtypes of advanced breast cancer. Neither of these medicines is funded for New Zealanders yet. You can read more about this here.
Although trastuzumab deruxtecan was designed to target the HER2 receptor, it has now been shown to be effective in cases of ‘HER2-low’ breast cancer as well, with advantages even for those with triple negative breast cancer. New research is revealing the intricate cellular and molecular mechanisms behind this, enabling better use of this and other similar medicines. One speaker noted that “ADCs operate via complex mechanisms and there will be even greater opportunities for their use when we understand the dynamics better.”
CDK 4/6 inhibitors for early breast cancer
CDK 4/6 inhibitors such as palbociclib, ribociclib and abemaciclib are proven treatments, shown to extend life with advanced HR+ breast cancer. New evidence shows that these drugs can also be used to treat early HR+ breast cancer, with abemaciclib now approved by the FDA for this use.
SERDs (oral selective oestrogen receptor degraders), like fulvestrant, are important medicines for treating HR+ breast cancer. Latest data from trials with a number of new medicines in this class were presented at SABCS, showing a deeper understanding of how these medicines work and promise for new treatment options. Names to look out in the future for include elacestrant (clinical trial name EMERALD), camizestrant (trial SERENA-2), imlunestrant (trial EMBER), and giredestrant (trial acelERA).
Current issues for patient advocates
Although SABCS is a research conference, attendance by patient advocates is strongly encouraged and it is clear that their voices are valued by the researchers, the FDA and the pharmaceutical companies represented at the meeting. Most attendees are from the US and it was interesting to hear their concerns, even though their health system is quite different from ours.
Financial toxicity was a big issue. Americans need health insurance in order to afford health care, and it was clear that there was a wide variation in the amount of cover different people could access. While top-of-the-line care, incorporating all of latest treatments, is an option for well-insured Americans, others are not so fortunate. Advocates also expressed concern the amount of information available to patients and the standard of knowledge about breast cancer treatments among clinicians practising at “community cancer clinics”.
Black US breast cancer advocates and young women with breast cancer had much higher profiles at this SABCS than the one I attended in 2017, with a number of organisations, such as the Tigerlily Foundation, set up to represent these women’s interests and to push for greater inclusion in clinical trials.
Global breast cancer research thriving
The vast amount of research presented at SABCS reassured me that globally, advances in breast cancer treatment are going to continue apace. However, I couldn’t help but reflect on how far behind many other countries New Zealand is in terms of affordable access to modern breast cancer medicines. Clearly, New Zealand patient advocates must continue to publicise our needs and push for meaningful lasting change.
Louise Malone 31 December 2023