Subtleties And Future Questions
Several factors have to be carefully considered in interpreting the trial results, explained Dr. Apolo.
A major one is that the study did not directly compare survival between people who got avelumab immediately versus when their cancer progressed. Only about half of the participants who initially received supportive care alone went on to receive immunotherapy after their cancer got worse. There could be many reasons for this, including lack of access to these drugs in different countries, Dr. Apolo said.
But it also might be that, for some people, the cancer was progressing too rapidly, she added. When these tumors start growing, they start growing very quickly. So if you wait to start at the time of progression, maybe its too late, added Dr. Apolo.
Not all patients will be caught by the second-line safety net, agreed Dr. Plimack.
So, for now, said Dr. Balar, the takeaway message from the JAVELIN study is after chemotherapy, dont wait to give immunotherapy.
But more and more, studies are looking at whether some patients should receive immunotherapy as first-line treatment, he continued. Immunotherapy is one of the most important advances weve made in the last 30 years, Dr. Balar said.
The JAVELIN results cant provide any insight into which patients benefit from first-line treatment with a platinum-based chemotherapy, he added. This trial wasnt designed to ask: Is chemotherapy necessarily the best choice for every patient? he explained.
Intravesical Therapy For Bladder Cancer
With intravesical therapy, the doctor puts a liquid drug right into your bladder rather than giving it by mouth or injecting it into your blood. The drug is put in through a soft catheter that’s put into your bladder through your urethra. The drug stays in your bladder for up to 2 hours. This way, the drug can affect the cells lining the inside of your bladder without having major effects on other parts of your body.
Keytruda Bests Chemotherapy In Overall Survival Rates For Bladder Cancer
Keytruda produced better overall survival rates than chemotherapy for patients with recurrent, advanced urothelial carcinoma.
Ronald de Wit M.D., Ph.D.
Keytruda produced better overall survival rates than chemotherapy for patients with recurrent, advanced urothelial carcinoma, according to a phase 3 KEYNOTE-045 study presented at the 2017 European Society of Medical Oncology Congress.
As of the cutoff point on May 19, 2017, median follow-up was 22.5 months in both arms. The median OS was significantly longer with Keytruda compared to chemotherapy in the overall patient population median OS was 10.3 versus 7.4 months, respectively.
Significantly improved OS was observed regardless of the level of PD-L1 expression a biomarker associated with better responses to Keytruda as measured by combined positive score , with patients having CPS 10 percent or higher demonstrating a median OS of 8.9 with Keytruda versus 5.2 months with chemotherapy.
The 18-month OS rates were 33.2 percent compared to 19.7 percent with Keytruda versus chemotherapy, respectively.
Importantly, OS was longer with Keytruda versus chemotherapy regardless of age, liver metastases, hemoglobin levels, the presence of visceral disease and the choice of chemotherapy.
Similar progression-free survival was observed between the treatments median PFS was 2.1 versus 3.3 months with Keytruda versus chemotherapy, respectively.
The KEYNOTE-45 trial was sponsored by Merck & Co, based in Kenilworth, New Jersey.
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Cancer Spreading To The Kidneys
This maintenance therapy continued for 5 years, until the doctors found that the cancer had spread to both of my kidneys. They recommended that my 2 kidneys be removed, which would mean I would have to go on dialysis for the rest of my life. I have had family members who were on dialysis, and I can assure you it is not a pleasant road.
For our peace of mind, my wife and I sought second and third opinions. We spent the summer traveling to different cancer centers at several universities, including Cornell University, NYU, Mount Sinai Hospital, and others. Every one of these cancer centers had a different assessment of my situation and a different recommendation.
Finally, the doctors at Winthrop University Hospital, who had successfully treated me before, said that I should only have my left kidney removed and leave the right kidney, which was still functioning at 80% capacity. They removed the left kidney and inserted a tube from my bladder directly into the right kidney. I then underwent 6 more rounds of BCG therapy, hoping to rid my body of any remaining cancer.
The New Keytruda Protocol
In April of 2020, the FDA approved a new dosing regimen for Keytruda. Instead of 200mg every three weeks, patients can now receive 400mg every six weeks!
We didn’t broach the idea of trying the new dosing amount last year because we wanted more data on patient symptoms and if it had any adverse reactions in bladder cancer patients specifically. Also, at the height of the pandemic, we didn’t want to try something new that may land me in the hospital.
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Top Story In Bladder Cancer: Pembrolizumab Monotherapy For Bcg
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Keytruda Improves Survival Of Advanced Bladder Cancer
CancerConnect News: Patients with recurrent urothelial cancer lived longer when they received Keytruda compared to chemotherapy as second-line treatment, according to long-term follow of a clinical trial presented at the Genitourinary Cancer Symposium.1
About Bladder Cancer
Bladder cancer will be diagnosed in approximately 77,000 people in the United States this year alone. The average age that patients are diagnosed with bladder cancer is 70 years, with 80% of these patients being former smokers. The most common type of bladder cancer is urothelial carcinoma, whereby cancer begins in the cells that line the bladder.
Urothelial carcinoma may involve parts of the kidney, bladder, and ureter . Urothelial carcinomas begin in the cells that line the particular organ in which the cancer develops. If detected and treated early, cure rates are high. However, once bladder cancer has spread outside of the bladder to distant sites in the body, effective treatment options remain limited, particularly if a patient experiences a cancer recurrence following prior therapies. Advanced bladder cancer refers to cancer that has spread outside the bladder to regional or distant sites in the body.
About The KEYNOTE-045 Clinical Study
Copyright © 2018 CancerConnect. All Rights Reserved.
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Substantial Improvement In Survival
Dr. Powles and his colleagues enrolled 700 people with locally advanced or metastatic bladder cancer in the international JAVELIN Bladder 100 study, which was funded by Pfizer, the drug’s manufacturer.
All trial participants had already received chemotherapywith either cisplatin and gemcitabine or carboplatin and gemcitabine, if their health did not allow them to receive cisplatinand their disease had not worsened during chemotherapy.
Participants were then randomly assigned to receive either maintenance treatment with avelumab plus supportive care or supportive care alone. People in the maintenance group received infusions of avelumab every 2 weeks until their cancer started growing again or they left the study for other reasons. Supportive care for both groups included pain management, nutritional support, and treatment of infections.
People in the supportive care group whose cancer got worse did not receive avelumab as part of the trial. However, they could receive it or any other immunotherapy drug after leaving the study.
Maintenance treatment with avelumab after chemotherapy turned out to have substantial benefits. The median overall survival for people who received maintenance avelumab was more than 21 months, compared with about 14 months for people who received only supportive care until their cancer got worse.
Choose The Right Doctor For You
It is also important to choose the right doctor. Just because someone is the best doctor in the world doesnt mean that this doctor is right for you. Every doctor works differently for every patient.
No matter how good your doctor is, you must do your own research to find the best doctor for you. Seek a second and third opinion, and find as many people as you can to support you during this challenging experience.
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Keytruda Has Been Proven To Help Patients With Advanced Urothelial Bladder Cancer Live Longer Compared To Chemotherapy
A clinical trial studied patients who were previously treated with platinum-containing chemotherapy for advanced urothelial bladder cancer, but whose therapy did not work or whose therapy had stopped working. Patients with autoimmune disease or a medical condition that required immunosuppression were not included in the trial. Nearly half of the patients included in the trial were given 200 mg of KEYTRUDA every 3 weeks through an intravenous line. The rest of the patients were given chemotherapy every 3 weeks .
Melanoma Drug Shows Promise
For the trial, Caroline Robert of Gustave Roussy and Paris-Sud University in France and colleagues treated 655 patients with advanced melanoma.
“These are patients whose disease cannot be surgically removed, cannot be cured by surgery and usually the majority of these patients have disease that involved vital organs,” said Dr. Stephen Hodi, a melanoma specialist at the Dana-Farber Cancer Institute who worked on the study.
Seventy-five percent of them had already been given other cancer treatments, including Yervoy, known generically as ipilimumab.
On average, the patients lived two years and 40 percent of them are still alive three years later. About 15 percent of these patients have whats called a complete remission, meaning there is no trace of their tumors. That doesnt mean a cure its too soon to say that but it does mean months or years of cancer-free life that they otherwise could not have hoped for.
And 61 of the patients, or 9 percent, have stopped taking the drug after their tumors went away. Virtually all of them are still in remission.
This is huge in the melanoma community, said Tim Turnham, executive director of the Melanoma Research Foundation.
It’s difficult to know at what point you call it a cure. For the patient, though, it means they are cancer-free and for some of those patients, it is likely that their cancer never will come back, Turnham told NBC News.
Keytruda’s being tested in other cancer types now.
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Keytruda Helped Completely Shrink Tumors In Some Patients With High
Results are from a clinical trial that included 96 patients who received 200 mg of KEYTRUDA through an intravenous line every 3 weeks. All of the 96 patients in the trial had high-risk NMIBC with carcinoma in situ . CIS means the tumor is flat and has not spread into the muscle of the bladder wall. All patients previously received Bacillus Calmette-Guerin treatment that did not work or stopped working. All patients were either not able to or decided not to have their bladders removed.
Advanced Bladder And Urinary Tract Cancer
Keytruda was evaluated in a clinical study of patients with urothelial cancer who had previously received a platinum-based chemotherapy regimen . For the patients receiving Keytruda, the chemotherapy had either never worked or stopped working. Overall, patients receiving Keytruda lived longer than those receiving chemotherapy.
- Patients were split into two groups of about 270 patients each. Each group was given either 200 mg of Keytruda every 3 weeks or chemotherapy every 3 weeks.
- At evaluation, 43% of patients were alive compared to 34% of patients receiving chemotherapy. Patients receiving Keytruda lived for 10.3 months compared to 7.4 months with chemotherapy.
- An equal number of patients in both the Keytruda and chemotherapy groups had their cancer spread, grow, or get worse. Half of patients on chemotherapy were alive at 3.3 months without their cancer spreading, growing, or getting worse, compared to 2.1 months with Keytruda.
- A greater number of patients receiving Keytruda had their bladder cancer tumors shrink compared to chemotherapy .
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Nice Rejects Keytruda For Advanced Bladder Cancer In Final Guidance
Treatment had been authorised for use in this indication via the Cancer Drugs Fund in 2018
The UKs National Institute for Health and Care Excellence has issued a second final appraisal document rejecting MSDs Keytruda for the treatment of advanced bladder cancer.
MSD known as Merck & Co in the US and Canada had initially been granted authorisation for Keytruda in advanced or metastatic urothelial carcinoma patients who had previously received platinum-based chemotherapy via NICEs Cancer Drugs Fund in 2018.
As part of the managed access agreement, further evidence could be collected for Keytruda in this indication, which was then reviewed by NICE as part of its final decision.
NICE decided not to issue a permanent recommendation for Keytruda in this patient population in March 2020, after results from the KEYNOTE-045 demonstrated a benefit for overall survival but not for progression-free survival in the second-line setting.
Following this rejection, MSD appealed the decision, although NICE has upheld its previous guidance not to recommend Keytruda as a second-line treatment for advanced bladder cancer patients.
In a statement issued today, NICE said that although evidence shows Keytruda meets its life-extending treatment criteria, the cost-effectiveness estimate for the immunotherapy is uncertain.
NICE said in its own statement that it now recommends Roches anti-PD-L1 drug Tecentriq for bladder cancer patients at this stage of the treatment pathway.
What Has Been Msks Contribution To This Trial And Bladder Cancer Research
I was one of the lead investigators in designing this trial, and MSK was one of the sites enrolling patients in this multicenter study. Doing a randomized, double-blind trial with a control group receiving a placebo is very challenging and takes a long time. But it provides very solid results that you can be confident are significant.
MSK has been a leader in bladder cancer research, especially in the use of therapies before and after surgery for muscle-invasive disease. In 2018, the National Cancer Institute awarded MSK a prestigious SPORE grant for bladder cancer research. This grant is overseen in tandem by myself and medical oncologist David Solit. One project, led by medical oncologist Jonathan Rosenberg, seeks to understand what exactly causes urothelial cancer to respond to or resist immunotherapy drugs. We hope this research can lead to more successful clinical trials like CheckMate 274.
Another project, led by Dr. Solit and medical oncologist Gopa Iyer, investigates whether people with muscle-invasive bladder cancer can avoid having their bladders removed. Some people have bladder tumors with genetic changes called DNA-damage response mutations. Research has shown that these people usually respond especially well to chemotherapy before surgery.
MSK has many experts in genetics, molecular oncology, and immunology who can work closely to produce insights that can advance the field. We plan to continue improving the outlook for many people with this disease.
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Immunotherapy Clinical Trial Puts Bladder Cancer Survivor On Road Torenewed Health
After Ron Speidel retired, he and his wife, Brenda, ventured around the U.S. in their RV for nine years.
Then I got the big C, says Ron, 70. After playing college football as an athletic youth in Cape Girardeau, Missouri, he served as a police officer for 30 years including 18 as a K-9 handler in high-risk operations.
I was always very active, he says, noting his surprise when he discovered blood in his urine during a stay at his home in Mission, Texas. His physician sent him straight to a urologist in nearby McAllen, Texas, who confirmed his doctors suspicion of bladder cancer.
He said, Go to MD Anderson, the worlds leader. This is what they were founded on, Ron recalls.
Here, he met with genitourinary medical oncologist Jianjun Gao, M.D., Ph.D., who prescribed an arduous chemotherapy regimen , as well as urologic surgeon Brian Chapin, M.D., who subsequently operated on him.
Facing bladder cancer metastasis
Ive been shot at, stabbed, went out looking for bad guys I knew were armed but this was the worst situation I had faced, Ron says of his diagnosis. It took its toll. He toughed it out, though, and got a clean bill of health. Because bladder cancer frequently returns, Rons care team continued to monitor him with checkups, labs and scans every three months. After a year had passed, Gao told him that the cancer had returned and metastasized to the bone.
The Speidels had renewed hope when Ron met the criteria and was enrolled.
Stage Iii Bladder Cancer
My doctors at Winthrop University Hospital in Garden City, Long Island, told me that I had stage III bladder cancer, and that it was very aggressive. They said that most likely, the cancer had penetrated the walls of my bladder, and I would have to have the bladder removed by surgery and be replaced with a constructed bladder.
When the surgery was over, however, they gave me great news: the cancer was not as bad as they had thought, and I was able to keep my bladder.
About 2 months after surgery, I began a treatment called Bacillus Calmette-Guérin, or BCG, which is used in some patients with bladder cancer to prevent the cancer from growing and coming back. My doctors believed that the cancer might have moved to other parts of my body, and they wanted to be sure that the BCG treatment would remove any remaining cancer cells in my body.
After I received 6 rounds of BCG therapy, my doctors recommended that I go to Memorial Sloan Kettering Cancer Center in New York City for a maintenance program, which is a standard treatment after BCG therapy to prevent cancer recurrence. So, every 3 months, the doctors at Memorial Sloan Kettering would have me do urine tests, blood tests, and a cystoscopy.
And every time, they found some lesions with cancer, and I would go for a one-day surgery to remove the lesions with the cancer. Once the lesion or lesions were removed, I was clear to go back home.
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