What's new in cancer?: Immunotherapy, ADCs and BRCA genetics
The cancer community is often the first to learn about developments in cancer by attending major research conferences. Over the past year, many of these events embraced a virtual or hybrid model, but there's still a lot of exciting data to discuss. In the first of many blogs, Dr Richard Simcock, Consultant Clinical Oncologist, rounds-up of some of the most significant developments
1. Antibody dependent conjugates
Artificially manufactured antibodies that attack certain cancers have been used to treat cancer for over a decade. Some cancer cells have specific proteins on their surface (antigens), which can be located by these purpose designed antibodies. Monoclonal antibodies (or MABs) for example are routinely used in the treatment of breast cancers (Trastuzumab), lymphoma (Rituxumab) and ovarian cancer (Bevacizumab).
More recently, the technology has been updated with the arrival of antibody-dependent conjugates (or ADCs). ADCs use the antibody as a delivery system that seeks out and connects to the cancer cell containing the relevant antigen. Connected to the antibody by small linkers are small molecules of chemotherapy. When the antibody and antigen connect, the ADC enters the cell. Shortly after, the linker dissolves and the chemotherapy becomes active inside the cell. This smart delivery system allows very small amounts of chemotherapy be delivered to exactly the right place and reduces side effects.
There are already a few ADCs being used to treat blood cancers and breast cancer. We now have new data showing increased effectiveness of this treatment in Her2+ breast cancer and Her2+ stomach cancer. One exciting development was the approval of a new ADC to treat triple negative breast cancer. ADCs rely on finding an antigen that the antibody can attach to, but triple negative disease lacks the hormone receptor and the Her2+ targets that are frequently used in breast treatment. This is an area where new drugs are needed.
The ADC Sacituzumab govitecan (Trodelvy) has been shown to lengthen survival in people with advanced triple negative breast cancer. The drug is not yet available in the UK, but it represents an important step in designing new drug treatments for cancer.
The huge excitement that greeted the introduction of immunotherapy was based on the incredible results these treatments produced for some patients with melanoma and specific lung cancers. Some of these drugs have been available in the NHS since 2015. Since then, immunotherapies have been developed and tested in a wide range of cancers. In the last year, we have also discovered that immunotherapy may be useful in treating thymic cancer and advanced cervical cancer.
Nasopharyngeal cancer (affecting the back of the nose) is a relatively rare cancer in the UK, although it is much more common in Hong Kong and China. If the disease recurs after radiotherapy, the treatment options are limited. It is therefore pleasing to see that the immunotherapy, Toripalimab, improves survival compared to standard chemotherapy in these patients. The assessment and approval of this drug for use in Europe is awaited.
While immunotherapy treatments are a promising development for people with cancer, the costs of these drugs are staggering (spending in England on just one drug, Pembrolizumab, was £142.4 million in 2017). Most of these drugs are made and manufactured by European and USA based pharmaceutical companies, but a Chinese-backed company has now shown their immunotherapy, Sugemalimab, is effective in treating certain types of lung cancer. What is most interesting about the company behind the drug is its ambition to undercut the price of these treatments. This development is being watched keenly to see if it causes a fall in drug prices.
3. Cancer genetics and BRCA
We have known for many years that people born with a mutation in the BRCA1 or BRCA2 gene have a higher risk of developing breast and ovarian cancer. In the past, this information has been used to help counsel people with BRCA-related cancers and their families about risk reduction and surveillance. This includes surgery to remove the ovaries or breasts as a preventative strategy.
Advances in our scientific understanding of BRCA, particularly how cells become faulty when the BRCA gene mutates, is now leading to the development of drugs specifically targeted at these faulty cells. These drugs are called PARP inhibitors.
One of these drugs, Olarapib, has recently been tested in a large and successful trial. In this study, 1836 people with an inherited BRCA mutation and a breast cancer diagnosis were given either a placebo or Olarapib treatment for one year after completing all their usual therapies for breast cancer. The group treated with Olarapib have had much lower recurrence rates of their cancer. Regulatory authorities will be looking at the drug for approval as this data develops.
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