The cancer wonder drugs making waves in the world of oncology
While cancer continues to claim 167,000 lives every year in the UK and ten million worldwide, research on a variety of treatment options is continually improving and expanding.
Only last week, we learnt of the results of a clinical trial which found that the drug Enhertu doubled average survival rates in women with breast cancer. Another revealed that after taking Dostarlimab, all patients in the drug trial seemed to be in remission. Then there were the results from the Phase I study involving a custom-made mRNA vaccine for pancreatic cancer, which produced promising results for the deadliest of cancers in a small initial trial.
Here’s what you need to know about the three “wonder drugs” making waves in the world of oncology:
Trastuzumab deruxtecan (Ehertu): for metastatic breast cancer
When the results from the Enhertu clinical trial were presented at the annual meeting of the American Society of Clinical Oncology and published on Sunday in the New England Journal of Medicine, cancer specialists heralded a “new standard of care” that had the potential to change how medicine is practised.
The clinical trial, sponsored by the pharmaceutical companies Daiichi Sankyo and AstraZeneca and led by Dr Shanu Modi, found that the experimental drug trastuzumab deruxtecan (sold as Enhertu), resulted in “significantly longer progression-free and overall survival than the physician’s choice of chemotherapy.”
Enhertu consists of an antibody that seeks out the HER2 protein on the surface of the cells. The antibody is then attached to a chemotherapy drug. When trastuzumab deruxtecan locates a cell with HER2 on its surface, it enters the cell, and the chemotherapy drug slices the antibody and eliminates the cell. What makes trastuzumab deruxtecan unique is that it seeps through the cells’ membrane, and from there it can move into nearby cancer cells and kill them as well.
Trastuzumab deruxtecan was already approved for those with HER2-positive breast cancer, but few expected it to work as drugs for such cancers had previously failed in HER2-low patients.
However, in the trial, researchers analysed 557 patients with metastatic breast cancers categorised as HER2-low and found that, of the patients who took Enhertu, tumours stopped growing for about ten months, as compared with five months for those with standard chemotherapy. The patients who took the experimental drug also survived for 23.9 months, compared to 16.8 months for those who received standard chemotherapy.
“It is unheard-of for chemotherapy trials in metastatic breast cancer to improve survival in patients by six months,” Dr Moore, who enrolled some patients in the ground-breaking study, explained to the New York Times.
Dr Kotryna Temcinaite, a senior research communications manager at Breast Cancer Now, also welcomed the news, telling Reaction: “With an estimated 35,000 people living with secondary (metastatic) breast cancer in the UK, we urgently need to find new ways to treat this devastating disease. It’s hugely exciting trastuzumab deruxtecan (Enhertu), which is already being used on the NHS to treat women with HER2 positive secondary breast cancer, may benefit even more breast cancer patients giving the hope of additional precious time with their loved ones.”
Dostarlimab (Jemperli): for rectal cancer
A small clinical study trial at New York’s Memorial Sloan Kettering Cancer Center of the immunotherapy drug Dostarlimab (sold as Jemperli) has produced “unprecedented” results. It found that all of the patients with a specific subtype of rectal cancer entered remission after taking Dostarlimab over a six-month period.
“I believe this is the first time this has happened in the history of cancer,” said Dr Luiz Diaz, an oncologist and one of the lead authors of the paper, published in The New England Journal of Medicine.
Dostarlimab is a monoclonal antibody used to treat endometrial cancer, but the trial was a clinical investigation into whether it could be effective against rectal cancer tumours. These tumours, known as “mismatch repair deficient”, are a subset of rectal cancers which have an increased mutation rate and have been known to be sensitive to immunotherapies. The drug blocks a cancer cell protein that inhibits the immune system and thereby switches on anti-cancer activity in the immune system.
For this research, 12 patients with mismatch repair-deficient rectal cancer received Dostarlimab every three weeks for six months. The standard treatment for this condition would be chemotherapy with radiation (chemoradiation), followed by surgery.
However, after treatment with Dostarlimab, scans that once spotlighted discoloured tumours instead morphed into smooth, pink tissue, and there was no indication of cancer in physical examination, radiological scans or biopsies.
Thus far, with participants having been treated up to two years ago, all are cancer-free, and none have needed the follow-up treatment of chemoradiotherapy or surgery.
Professor Daniel Hochhauser, a professor of medical oncology at UCL Cancer Institute, said: “Immunotherapy is the major growth area in cancer therapy and has already been effective in a variety of cancers including melanoma and non-small cell lung cancer.
“But what is interesting about this study, is that these are rectal cancer patients who would typically require surgery and chemoradiation. These treatments can result in long-term morbidity including bladder function, sexual health and fertility.”
He added: “What is remarkable is that a percentage of rectal cancer patients can avoid these potentially debilitating treatments. The results illustrate the immense power of immunotherapies to completely overturn accepted treatments. The next step would be a larger study, and if the results are further confirmed, it could be transformative for some patients with rectal cancer.”
mRNA vaccine: for pancreatic cancer
A custom-made mRNA vaccine for pancreatic cancer, called autogene cevumeran, has produced promising results in a small initial trial involving people whose cancers were detected early enough to operate on. The results were announced by the Pfizer vaccine developer BioNTech which used the same technology to stop the disease from returning.
In the Phase I trial, 16 people were given the vaccine around nine weeks after having an operation to remove their tumours. In half of the patients, the vaccine did not elicit an effective immune response, and the cancers returned, but in the other half, the vaccine did elicit a good response, and they remained cancer-free 18 years later.
Like the mRNA vaccines against Covid-19, the aim is to get the immune system to target and destroy any cells producing harmful proteins. The mRNA approach begins with removing a tumour so that the DNA of the cancer cells is sequenced and compared with healthy cells from the same individual. BioNTech then looks for proteins that have mutated in the cancer cells and distinguishes these cells from healthy ones. The vaccines use an mRNA, a genetic code from the tumour, which is injected into an individual to trigger the immune system to attack tumour cells and keep the disease at bay.
Dr Vinod Balachandran, principal investigator at the Memorial Sloan Kettering Cancer Center, said: “Unlike some of the other immunotherapies, these mRNA vaccines do appear to have the ability to stimulate immune responses in pancreatic cancer patients. So we’re very excited about that, and the early results that suggest that if you have an immune response, you may have a better outcome.”
Pancreatic cancer has the highest mortality rates of all the cancers, and according to Cancer Research UK, a mere 7.3 per cent of patients survive five years after being diagnosed. While this was a very small initial trial, there is hope that longer follow-ups and more extensive trials could break new ground for an mRNA-based cancer vaccine treatment for hard-to-treat tumours.
Earlier this year, Health Secretary Sajid Javid waged a “war on cancer” in a bid to support a decade-long cancer plan in England. Building on the NHS long-term plan, Javid set out a range of targets, from improving research on new early diagnostic tools to catch cancer at an early stage to intensifying research on mRNA vaccines and therapeutics for cancer.
The new research raises hopes that, under the government’s 10-year cancer plan, such treatments and vaccines could become available on the NHS, allowing us to ramp up our battle against cancer.