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Ronny Allan
Background
Following the Americal Society of Clinical Oncology (ASCO) conference in June 2022 (ASCO is the biggest Oncology event in the world), the media widely featured the results of the Phase 2 clinical trial of the drug Dostarlimab, an anti–PD-1 monoclonal antibody. The media often looks for headline-grabbing stories and this was one of them. One UK TV outlet said they may have found the cure for cancer, which is a reckless statement when you look at the size and boundary of the clinical trial referenced. The detail is, that this was a phase 2 trial for “rectal adenocarcinoma”, but specifically locally advanced mismatch repair-deficient (dMMR) rectal cancer, allowing them to avoid surgery, chemotherapy, and radiation, at least for the time being. Nonetheless, the complete response in all 12 was clinically significant. The abstract summary of this trial was published in the New England Journal on the day of the presentation at ASCO. Worth emphasising this study was targeting “locally advanced” cancer, i.e. cancer that has spread from where it started to nearby tissue or lymph nodes. It is not stage IV.
What is Dostarlimab?
(From National Cancer Institute) – A drug used to treat adults with endometrial cancer or other solid tumors that have come back or are advanced and have certain mutations (changes) in genes involved in DNA repair. It is used in patients whose cancer got worse during or after other treatment. It is also being studied in the treatment of other types of cancer. Dostarlimab binds to a protein called PD-1, which is found on T cells. Dostarlimab may block PD-1 and help the immune system kill cancer cells. It is a type of monoclonal antibody and a type of immune checkpoint inhibitor. Also called Jemperli.
What are Monoclonal antibodies?
Monoclonal antibody therapy is a kind of immunotherapy that empowers the body’s immune system to attack cancer cells.
Our body produces billions of different kinds of antibodies, which are part of the immune system. They have specific archnemeses in the immune system that they target, such as pathogens like diseased cells or viruses. Monoclonal antibodies used in cancer treatment are designed in a lab to target certain antigens — foreign substances in the body — that live on the surface of cancer cells. By targeting those antigens, the antibodies are able to latch onto the cancer cells and act as a “call to arms” for other disease-fighting warriors in the immune system.
What is dMMR?
dMMR stands for deficient MisMatch Repair. It’s a “biomarker” and these may be used to better understand some of the characteristics of your cancer. What I could not find out is how likely are Neuroendocrine Neoplasms to be sensitive to this biomarker and therefore suitable for drugs which work better in tumours positive for this biomarker. There is also linkage with dMMR and MSI-H. MSI-H is short for High levels of MicroSatellite Instability.
MSI-H/dMMR can occur when a cell is unable to repair mistakes made during the division process. Normal cells have a system that sees and repairs mistakes that happen when the DNA is copied. It’s called the mismatch repair system. Sometimes the system stops working properly. When this happens, errors in the DNA start accumulating and may cause cancer. MSI-H/dMMR can be hereditary or random. Doctors use two types of tests to determine if tissue is positive for the MSI-H/dMMR biomarkers:
• Immunohistochemical staining (IHC) uses the tumor tissue from the biopsy
• Polymerase chain reaction (PCR) tests compare tumor tissue from the biopsy to a normal tissue to measure microsatellite instability
These tests may not be readily available in your country.
What about Neuroendocrine Neoplasms?
There is currently no real evidence of the efficacy of Dostarlimb in Neuroendocrine Neoplasms but some trials are based on MSI-H/dMMR positive solid tumours and may therefore include the possibility of Neuroendocrine Neoplasm involvement. However, sometimes this possibility may be hidden amongst the anatomised descriptors commonly used by doctors and scientists, e.g. pancreatic cancer, lung cancer, stomach cancer, etc (annoying but a fact). An example of a solid tumour trial featuring the use of Dostarlimb is NCT02715284. The interim results of this particular trial do not show the amazing response rates featured in the Rectal Cancer trial currently making the news so it must be remembered that there is no single silver bullet that works for every cancer at every stage. That said, the figures are reasonable, but it is not clear if any Neuroendocrine Neoplasms patients were included.
I set about researching the trials database and came up with one mention of Dostarlimab in a combo treatment for Small Cell Lung Cancer (technically a Neuroendocrine Carcinoma) and other “high grade” Neuroendocrine Carcinomas. In fact, the clinical trial divides these two groupings into cohorts. The reason this one caught my eye was that there is no mention of dMMR/MSI positivity criteria which means a wider scope but only doctors would be able to confirm that assumption.
Read more about this trial here but please take note of the eligibility criteria (inclusion and exclusion). The trial is only taking place at M D Anderson Cancer Center Houston, Texas, US.
General Clinical Trials Disclaimer
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact. If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net
The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan.
Disclaimer
I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me.
Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.
Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.
Finally
Whenever I post about a trial or study, some people get excited without understanding that these new treatments and capabilities can very often take years to come to fruition and it’s also possible that clinical trials can be halted, or that national approval agencies will not approve the final product. Plus, not everyone will be eligible, so always check the exclusion and inclusion criteria in the relevant clinical trials document. Please bear that in mind when reading studies/clinical trials posted on RonnyAllan.NET
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