Our ambition as a charity is to stop breast cancer deaths, and this can only be achieved by improving treatments for secondary breast cancer. By developing new drugs and making best use of the ones we’ve already got, we can ensure that people can live with secondary breast cancer – and live well – for longer.
Last year saw results released from several clinical trials which are finding better ways to keep secondary breast cancer under control. In this blog we summarise the highlights from clinical trials in 2018, grouped by the type of breast cancer.
Below we run through drugs currerntly being assessed by the National Institute for Health and Care Excellence (NICE) and the Scottish Medicines Consortium (SMC) to decide whether they can be used by the NHS:
- CDK4/6 inhibitors
- PI3K inhibitrors
- Crizotinib for lobular breast cancer
- Neratinib - anti-HER2 therapy for ER positive breast cancer?
- Palbociclib and Herceptin
- Atezolizumab and nab-paclitaxel
- Sacituzumab govitecan
- Triple Negative Trial - carboplation vs docetaxel
Our Policy & Campaigns team recently gave a preview of which decisions we are expecting in 2019, and we include links throughout this blog.
If you have breast cancer and are considering taking part in a clinical trial, you should speak with your breast care team to discuss which trials you may be eligible for, as you may have to meet certain requirements to be able to take part in a trial. Lists of clinical trials open to people in the UK are available from the UK Clinical Trials Gateway and Cancer Research UK.
Clinical trials of drugs are designed to test the safety and effectiveness of a drug (or combinations of drugs) for a specific group of people. For some – particularly those with secondary breast cancer – they also represent an opportunity to potentially get access to new treatments on top of the ones they’re already receiving. The hope is that these treatments may stop their secondary breast cancer from getting worse, and possibly extend their life – although in clinical trials this is not guaranteed.
Anti-hormone drugs, like tamoxifen, and aromatase inhibitors such as anastrozole, are a key part of treatment for both primary and secondary oestrogen receptor (ER)-positive breast cancer (also known as hormone receptor positive breast cancer). For people with ER-positive breast cancer which has spread, chemotherapy and targeted treatments such as palbociclib and everolimus can also help keep the cancer under control for longer. Newer drugs are being developed and tested which are matched to a person’s tumour – for example, drugs which are designed for tumours which carry certain mutations in their DNA.
CDK4/6 inhibitors such as palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) are already being used in combination with aromatase inhibitors, as a first treatment for women with ER-positive secondary breast cancer. Now, these drugs are being tested in combination with a different anti-hormone drug called fulvestrant, in particular for women who have already had anti-hormone treatments for their secondary breast cancer.
• The combination of palbociclib with fulvestrant (Faslodex) was tested as a treatment for women who have already had anti-hormone therapy for secondary breast cancer in a trial called PALOMA-3. The final results showed that, when looking at all women in the trial, this combination did not provide a statistically significant increase in life-expectancy. However, a subgroup of women whose secondary breast cancer initially responded to anti-hormone therapy gained an average of 10 months of life from palbociclib with fulvestrant (39.7 months from the start of treatment, compared to 29.7 months with fulvestrant alone).
• Last year, we heard the results from two trials testing the combination of ribociclib and fulvestrant with women who’ve had either one or no previous anti-hormone treatments. In post-menopausal women, the MONALEESA-3 trial showed that ribociclib delays the time before the cancer gets worse by nearly eight months (to 20.5 months, compared to 12.8 months with fulvestrant alone). For pre-menopausal women, the MONALEESA-7 trial reported that ribociclib delays disease progression for this group of women by nearly 11 months (to 23.8 months from beginning ribociclib treatment, compared to 13.0 months without ribociclib).
The combinations of ribociclib with fulvestrant, and palbociclib with fulvestrant, for women with advanced ER-positive breast cancer are currently being assessed by NICE for use on the NHS. The decision for ribociclib is expected in August 2019, and the decision for palbociclib is expected in December 2019. We are also expecting a decision from NICE on the use of abemaciclib with fulvestrant very soon.
The SMC is also assessing palbociclib for use in the NHS in Scotland, with a decision due later this year.
PI3K inhibitors are a relatively new type of cancer drug, blocking a protein called PI3K which helps cells to grow and multiply. These inhibitors are particularly used for tumours which carry a fault in a gene called PIK3CA, which provides the instructions to make one part of the PI3K machinery. Mutations in the PIK3CA gene are very common in cancer, and occur in the tumours of about 40% of people (or 2 in 5) with ER-positive secondary breast cancer.
Last year, early results from two trials testing two PI3K inhibitors – taselisib and alpelisib – were announced. These drugs are being tested in combination with the anti-hormone drug fulvestrant, for women with tumours carrying PIK3CA-mutations, whose breast cancer has gotten worse or returned following treatment with an aromatase inhibitor.
• Taselisib, in combination with fulvestrant, is being tested in the SANDPIPER trial. Results from the trial showed that taselisib delays the progression of their breast cancer for an additional two months (to 7.4 months with taselisib, from 5.4 months with placebo).
• Alpelisib is being tested with fulvestrant in the SOLAR-1 trial. Results from the trial revealed that alpelisib delays disease progression by an additional 5.3 months (to 11 months with alpelisib from 5.7 months with the placebo). A further analysis from this trial showed that a blood test could identify people who would benefit from alpelisib by analysing whether the circulating tumour DNA carried a mutation in the PIK3CA gene.
A NICE appraisal for alpelisib in combination with fulvestrant for treating advanced ER-positive breast cancer with PIK3CA mutations is currently on hold, and is not due to recommence until early 2020.
Crizotinib for lobular breast cancer
Scientists from the Breast Cancer Now Toby Robins Research Centre at The Institute for Cancer Research in London showed that the drug crizotinib could be effective for treating people with secondary lobular breast cancer. The drug (also known as Xalkori) which is currently being used to treat lung cancer, blocks a molecule called ROS1, which represents a weak spot for cancers which have faults in the E cadherin protein, like lobular breast cancer. The results have led to a new clinical trial called ROLO for women with secondary lobular ER-positive breast cancer, which is being run from the Royal Marsden Hospital in London.
Researchers from China recently presented results from a trial testing a drug called chidamide – an inhibitor of a molecule called histone deacetylase (HDAC). The drug was being tested in combination with exemestane (Aromasin) for women with secondary ER-positive breast cancer, whose disease had gotten worse during treatment with anti-hormone treatments. The results of this trial showed that chidamide with exemestane delayed further progression of the disease by 3.6 months on average (to 7.4 months, compared to 3.8 months with exemestane alone). However, more research is needed to compare chidamide and other HDAC inhibitors to the current standard-of-care for this group of women – either everolimus (Afinitor) or palbociclib.
Neratinib – anti-HER2 therapy for ER-positive breast cancer?
Research released last year showed that some ER-positive secondary breast tumours can become resistant to treatments because of mutations which activate the HER2 receptor – making the ER-positive cancer more like HER2-positive. To treat these tumours, an anti-HER2 drug called neratinib is being tested in combination with fulvestrant in a small trial called SUMMIT. The results from this trial were promising, considering that the tumours of the people involved in the trial had already become resistant to several different treatments. For instance, 33% of tumours responded to the drug, with an average duration of response of nine months. However, larger trials are needed to fully assess how long the combination can delay further progression of the disease.
Herceptin, Perjeta and Kadcyla are a key part of treatment for people whose HER2-postive breast cancer has spread. Clinical trials are now testing whether these drugs can be used in combination with other therapies to control the disease for longer.
Palbociclib and Herceptin
A combination of Herceptin and palbociclib is being tested with women with secondary HER2-positive breast cancer, who had already been treated with at least two types of anti-HER2 therapy. Early results from the PATRICIA trial showed that the combination was most effective against tumours which were both HER2- and ER-positive. Genetic testing of the tumours revealed a group of women with ‘luminal type’ tumours, for which the combination was even more effective. The trial is continuing to recruit participants in Spain in order to fully assess the value of this combination.
Atezolizumab and Kadcyla
Atezolizumab, or Tecentriq – a type of immunotherapy called a ‘checkpoint inhibitor’ which blocks the tumour’s ability to hide from the immune system – is being tested in combination with the anti-HER2 treatment Kadcyla in the KATE2 trial. Sadly, the results from this trial did not show any benefit of this combination compared to Kadcyla alone.
For people with Triple negative breast cancer which has spread, chemotherapy still remains the main treatment option. However, clinical trials are exploring the potential of using immunotherapy drugs and targeted therapies such as PARP inhibitors for this broad group of tumours.
Atezolizumab and nab-paclitaxel
Atezolizumab in combination with the chemotherapy drug nab-paclitaxel (Abraxane) is being tested with women whose triple negative breast cancer has spread in the IMpassion130 trial. The latest results from the study showed that the combination was particularly effective for women whose tumours contained immune cells which over-produced the PD L1 protein, which is the case for about 40% of triple negative tumours. For these women, the combination delayed the progression of the disease by 2.5 months on average (to 7.5 months, compared to 5 months with paclitaxel alone). An early estimate of long-term survival, which needs to be confirmed as the trial continues, suggested that the combination may also extend life by nearly 10 months.
Atezolizumab in combination with nab-paclitaxel for women with advanced triple negative breast cancer is currently being assessed by NICE for use on the NHS, with a decision expected in November 2019.
We’ve recently heard that this combination will be made available to certain women with secondary triple negative breast cancer through an Early Access To Medicines Scheme.
A new drug called sacituzumab govitecan has been tested for people with secondary ‘HER2-negative’ breast cancer – that is, either ER-positive or triple negative disease. Sacituzumab govitecan is a ‘smart drug’ which delivers a chemotherapy drug SN-38 straight to cancer cells which have the protein Trop 2 on their surface, which is the case in many types of cancer. Results from an early stage trial showed that the treatment could be beneficial for treating people with HER2-negative tumours who have already had several treatments for their breast cancer. In this small trial, a third (33%) of triple negative tumours responded to the drug, and the average duration of this response was nearly eight months. More research is needed to fully evaluate the effectiveness of the drug, but for people who have already received several different treatments for the secondary cancer, this could provide a new option in the future.
Triple Negative Trial – carboplatin vs docetaxel
Finally, our very own Prof Andrew Tutt set out to determine what was the most effective chemotherapy treatment for women with advanced triple negative breast cancer in the Triple Negative Trial (TNT). The results published last year showed that women who carry a BRCA mutation benefited more from carboplatin than from docetaxel (Taxotere) – about 10% of women with triple negative disease. For women with BRCA¬-mutated advanced TNBC, carboplatin delayed the progression of the disease by roughly an extra two and half months (6.8 months with carboplatin, compared to 4.4 months with docetaxel). In direct response to the TNT results, the European Society for Medical Oncology (ESMO) recently updated their guidelines to include that BRCA-mutated triple negative secondary breast cancer should treated with a ‘platinum’ chemotherapy drug like carboplatin.
Progress is being made all the time in research – though we know that for far too many people with secondary breast cancer, advances like the ones above come too late. We will not stop funding new research, and campaigning for access to the newest medicines, until breast cancer has taken its last life.
You can keep up to date on the latest developments in breast cancer research here on the blog – such as our round-up of last year’s San Antonio Breast Cancer Symposium.
You can also find out about how you can help make sure people with secondary breast cancer get access to the drugs they need, by signing up to our campaign updates.