CNN –
A new combination of cancer drugs appears to extend overall survival in patients with advanced bladder cancer more than the chemotherapy regimens currently used as standard treatment.
The study, presented on Sunday at this year’s European Society of Medical Oncology Congress in Madrid, suggests that a combination of the antibody drug enfortumab vedotin and the immunotherapy pembrolizumab, administered through intravenous infusions, reduces the risk of disease progression or death 55% reduction in patients with advanced bladder cancer who were not previously treated and whose cancer has spread to other parts of the body Overall survival averaged 31.5 months versus 16.1 months with standard chemotherapy.
This is one of several new studies examining ways to improve bladder cancer treatment.
“The problem with chemotherapy is that although it works quite well initially, resistance arises quickly and the median survival time for metastatic bladder cancer is about a year,” said Dr. Thomas Powles, Professor of Urological Cancers at the University of London and Director of Barts Cancer Center in the UK, who presented the research this weekend.
“This study showed that we conducted a large, randomized phase 3 trial comparing a new treatment – two new drugs – with standard chemotherapy,” Powles said. “And in this randomized trial, when you gave these two drugs together, you reduced the risk of death from this cancer by over 50%. So you’ve doubled the survival rate, patients are living twice as long, and we’ve achieved long-term, durable remission.”
Globally, bladder cancer is the sixth most common cancer in men and the disease kills about 200,000 people each year, many of whom die from advanced disease that has spread beyond the bladder. Treatment options usually depend on the stage of the disease, but may also include surgery or common chemotherapy drugs such as carboplatin or cisplatin.
And the new research – funded by U.S. drugmakers Seagen, Inc., Astellas Pharma and Merck & Co. – comes at a time when the United States is facing a significant shortage of platinum-based chemotherapy drugs, including carboplatin and cisplatin.
The phase 3 trial included 886 patients who were randomly assigned to receive either three-week cycles of the combination of enfortumab vedotin and pembrolizumab, given as IV infusions, or a chemotherapy called gemcitabine with cisplatin or carboplatin.
The study found that the new drug combination had a similar safety profile to the chemotherapies, with 55.9% of patients taking the combination experiencing side effects such as skin rashes or hyperglycemia, compared to 69.5% of those taking platinum chemotherapy received.
“We only got the data three weeks ago, so it’s happening very, very quickly,” Powles said, adding that the next step for the research team is to submit its data to the U.S. Food and Drug Administration and other agencies around the world to convey to the world. The data has not yet been published in a peer-reviewed journal.
“Because it is so conclusive, we don’t need to do a larger study. We now need to quickly convert this into patients, so we need to contact the authorities – the FDA in the United States, the EMA in Europe and around the world,” he said. “We need to get approval quickly.”
The research from Powles and his colleagues has the potential to change the standard of care for advanced bladder cancer, said Dr. Toni Choueiri, director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, who was not involved in the new paper, but is attending the ESMO congress in Madrid.
“Since I was in medical school, treatment for metastatic bladder cancer has been gemcitabine and platinum. We called it Gemcis or GemCarbo. Since the late 90s there has been nothing better than this on the front lines. But now the combination of pembrolizumab, an immunotherapy checkpoint blocker, and enfortumab vedotin, an antibody-drug conjugate, far surpasses the old therapy we had since the late 1990s,” Choueiri said. “I think this will be a new standard.”
Some other new studies looked at new ways to treat a different group of patients with advanced bladder cancer – patients whose disease continued to progress after one or two previous treatments.
Another phase 3 trial found that targeted therapy was effective in patients with advanced or metastatic urothelial cancer who had certain gene mutations. Urothelial cancer is a type of bladder cancer that begins in the urothelial cells that line the inside of the bladder. Almost all bladder cancers are urothelial carcinomas.
The study, published Saturday in the New England Journal of Medicine, compared the overall survival of 136 patients given the cancer drug erdafitinib as an oral pill with 130 patients given standard chemotherapy. The patients whose cancer had previously been treated with other forms of therapy were observed for an average of 15.9 months.
“Cisplatin-based chemotherapy is the standard treatment for newly diagnosed advanced and metastatic urothelial cancer. However, more than 50% of patients with metastatic urothelial carcinoma are ineligible for cisplatin treatment, and those who receive chemotherapy typically progress within a few months,” write the researchers from MD Anderson Cancer Center the University of Texas and other US institutions in the study. The phase 3 study was funded by the drug manufacturer Janssen.
“Erdafitinib therapy resulted in significantly longer median overall survival than chemotherapy in patients with advanced or metastatic urothelial carcinoma,” the researchers wrote, noting that median overall survival in patients receiving erdafitinib therapy was 12.1 months, versus 7. 8 months for those on chemotherapy.
In 2019, the U.S. Food and Drug Administration granted accelerated approval to erdafitinib for patients with locally advanced or metastatic bladder cancer who have certain gene mutations and whose cancer progresses during or after chemotherapy. The drug was the first therapy targeting a genetic modification to be approved by the FDA to treat patients with the most common type of bladder cancer, metastatic urothelial cancer.
Erdafitinib, a kinase inhibitor drug, blocks the action of the protein that signals cancer cells to multiply, essentially slowing or stopping the spread of cancer cells, according to the National Library of Medicine. The incidence of treatment-emergent adverse events in the phase 3 study was similar in patients taking erdafitinib as in patients receiving chemotherapy. However, events leading to death were less common with erdafitinib than with chemotherapy, occurring in 0.7% of erdafitinib patients versus 5.4% of chemotherapy patients.
“A new standard approach”
Another study published Sunday in the New England Journal of Medicine and presented at the ESMO meeting found that the use of chemotherapy in combination with immunotherapy drugs resulted in improved survival rates in patients with previously untreated advanced bladder cancer, compared with one chemotherapy alone.
This phase 3 study was conducted in 608 patients with advanced bladder cancer that has spread or cannot be removed surgically and has not been previously treated. Half of them received intravenous infusions of the immunotherapy drug nivolumab plus the chemotherapies gemcitabine and cisplatin every three weeks for up to six cycles, followed by nivolumab every four weeks for a maximum of two years. The other half received gemcitabine-cisplatin alone every three weeks for up to six cycles. Researchers found that grade 3 or higher adverse events — such as anemia or urinary tract infections seen in a phase 2 trial — occurred in 61.8% of patients who received the nivolumab combination, versus 51.7 % of patients who received chemotherapy.
The researchers from Mount Sinai and other international institutions found that the overall survival rate was a median of 21.7 months with nivolumab combination therapy, compared with 18.9 months with gemcitabine-cisplatin alone. The study was funded by drugmaker Bristol Myers Squibb in collaboration with Ono Pharmaceutical Company.
“So far, no new active ingredient as an adjunct to first-line standard cisplatin-based chemotherapy has improved overall survival in metastatic urothelial carcinoma,” said study author Dr. Matthew Galsky, co-director of the Center of Excellence for Bladder Cancer at the Tisch Cancer Institute at Mount Sinai, said in a press release. “These results support nivolumab plus cisplatin-based chemotherapy as a new standard approach for the treatment of metastatic urothelial cancer.”