Researchers at the Tisch Cancer Institute have found that a certain type of chemotherapy improves the immune system's ability to fight bladder cancer, particularly when combined withimmunotherapyThese findings may explain why the approach, cisplatin chemotherapy, can lead to a cure in a small subset of patients with metastatic or advanced bladder cancer.
The researchers also believe their findings could explain why clinical trials combining another type of chemotherapy, carboplatin-based chemotherapy, with immunotherapy have been unsuccessful, but others using cisplatin with immunotherapy have been success.
The results of the study were published in Cell Reports Medicine.
That's why bladder cancer responds better to immunotherapy
“We have known for decades that cisplatin works better than carboplatin in bladder cancer, however, the mechanisms underlying these clinical observations have thus far remained elusive,” said lead study author Matthew Galsky, MD, co-director of the Center of Excellence for Bladder Cancer at the Tisch Cancer Institute at Mount Sinai.
“This study provides clues as to why cisplatin-based chemotherapy can achieve durable disease control in a subgroup of patients with metastatic bladder cancer, provides clues as to which patients may derive such benefit, and provides a basis for building treatment regimens. even better ones that exploit the immunomodulatory effects of cisplatin-based chemotherapy.”
Bladder cancer affects approximately 83,000 people in the United States each year. Metastatic bladder cancer is particularly difficult to cure with current treatments, so these findings represent an important step in making the most effective use of available drugs and determining effective combination therapies.
The study found that cisplatin chemotherapy may work better when the body has generated a pre-existing, but limited, immune response against the tumor. The study also found that cisplatin damages DNA in cancer cells, which can lead to changes in gene expression that could improve the body's immune system's ability to detect cancer cells
This research was part of a large scientific team effort using biological samples from an international Phase III clinical trial involving multiple institutions.
After 40 years of treating metastatic bladder cancer with chemotherapy as the primary treatment, scientists now present a new approach using immunotherapy combinations. The results of two studies were presented at the European Society of Medical Oncology (ESMO) conference in Madrid. The results of these studies could revolutionize the landscape of bladder cancer treatment.
Traditionally, cisplatin-based chemotherapy has been the standard treatment for bladder cancer patients who are able to tolerate this drug. However, responses have been limited and lasting results are rare.
In recent years, two phase 3 clinical trials have been conducted studying the effects of combining immunotherapy with chemotherapy or with a new drug, enfortumab vedotin, for the treatment of bladder cancer (more precisely: urothelial carcinoma) . If successful, both studies show a significant increase in both overall survival and progression-free survival.
Medical oncologist Michiel van der Heijden from the Netherlands Cancer Institute (NKI) explains: “These results mark a milestone in bladder cancer research, providing the first evidence of a survival benefit of combination therapy involving bladder cancer inhibitors. immune checkpoint compared to chemotherapy”.
“This is an exciting development in our field, as these findings will fundamentally change the treatment landscape for advanced bladder cancer. It is a testament to the collaborative efforts of the researchers and, above all, the resilience of all the patients who participated in this study. ”
The CheckMate 901 study studied a new combination of the drugs nivolumab and gemcitabine-cisplatin and compared it with chemotherapy-only treatment. The results showed that patients treated with both drugs showed a 22% reduction in the risk of death compared to patients treated with chemotherapy alone.
The results also showed that the combination of nivolumab and chemotherapy led to a significant improvement in progression-free survival compared to chemotherapy alone.
During this presidential session of the ESMO, the results of another phase 3 of the same treatment line will be presented, featuring a new combination of an antibody-drug conjugate with immune checkpoint inhibition, using Enfortumab Vedotin + pembrolizumab.
This study also found a statistically significant and clinically meaningful improvement in overall survival and progression-free survival. These findings will be published in a scientific journal at a later date.
Both treatments still need to be registered and approved in the Netherlands for health insurance coverage, which means they won't be readily available yet. In the United States, the combination Enfortumab Vedotin + pembrolizumab is already available for a subset of bladder cancer patients, based on a phase 2 study.
Results from a clinical trial led by researchers at Barts Health NHS Trust and Queen Mary University of London show that a new drug combination doubles the overall survival of patients with widespread bladder cancer (metastatic bladder cancer).
The findings show that giving people with metastatic bladder cancer enfortumab vedotin (an antibody drug conjugate) and pembrolizumab (an immunotherapy drug) can prevent the disease from getting worse and help them live twice as long as those given it just chemotherapy.
These findings were presented in a plenary session at the European Society for Medical Oncology (ESMO) conference on Sunday 22 October.
The life expectancy for people with metastatic bladder cancer is only one year and the treatment they are given, chemotherapy, has not changed in 40 years. This new study, called EV302, involved nearly 900 people with the goal of changing that and developing the first new treatment for bladder cancer that has spread in nearly four decades.
The team found that the 442 people treated with this new combination of drugs (enfortumab vedotin and pembrolizumab) lived almost twice as long as the 444 people treated with chemotherapy (31.5 versus 16 months). Additionally, researchers showed that the risk of death was 53% lower in those treated with the combination, which was also associated with better disease control rates. And, encouragingly, the side effects of the drug combination were very similar to those experienced by people undergoing chemotherapy.
Professor Tom Powles, professor of urology oncology at Queen Mary University of London and director of the Barts Cancer Centre, led the study at Barts Health. Speaking about the findings, he said: “We've known for a long time that we need to improve people's chances of surviving bladder cancer.
This study achieved this goal dramatically. We showed that the combination of these two drugs helped people live twice as long.” compared to those receiving standard chemotherapy, with unprecedented responses. There is new hope in bladder cancer and I can't thank those who took part in the study enough for doing so.”
Paul Goodfellow was diagnosed with invasive bladder cancer in December 2019, just three months after retiring. His initial treatment consisted of 3 cycles of chemotherapy followed by major surgery to remove the cancer, which included removal of his bladder. “It was a big operation,” explains Paul. “For about a year, all my scans came back clear.”
“But in late 2021, I was told my cancer had spread. I was devastated, as was my entire family. I was offered a limited number of chemotherapy cycles which would hopefully stop the spread but would have a short term effect. It seemed to be the only option for me, so I was ready to start treatment.
“Then, a few days later, I received a call from the Macmillan specialist nurse who had looked after me before, during and after the surgery. She told me about a bladder cancer clinical trial at St Bartholomew's Hospital run by Professor Powles and his team. she asked me if I was interested in learning more and, with nothing to lose, I jumped at the chance.
“That's when I signed up for the EV302 study. I have been taking the new drug combination for 22 months. I am over the moon to say that I had an 80% response rate after just three cycles. My cancer is not gone, but the situation is not getting worse.
“Thanks to this test I feel really good. I get to spend time with my wife, family and dog that I didn't think I would have. I still walk about three miles a day and go on RV trips with my wife and sometimes our children and grandchildren join us.
“I couldn't have imagined the things we are doing and have done after the terrible news we received in 2021. These drugs are absolutely incredible and I
hope more and more people can benefit from these treatments in the future.”
#Bladder #cancer #type #chemo #works
