The FDA has approved the immunotherapy-boosting drug, ANKTIVA, to be used with the existing immunotherapy drug, Bacillus Calmette-Guerin (BCG). This new therapy is a step forward in providing better care for patients with nonmuscle-invasive bladder cancer who haven’t responded to Bacillus Calmette-Guerin treatment alone and reduces the need for bladder removal surgery.1
The treatment works for non-muscle invasive kind of bladder cancer and can improve on current treatments. The FDA approval means that AKTIVA is safe and that doctors in the United States are now able to incorporate it into their bladder cancer tool box.
Beating bladder cancer
Bladder cancer is a global concern, ranking as the 10th most common cancer worldwide. In the U.S. alone, over 83,000 new cases and 16,800 deaths are expected for 2024.3 The standard treatments for nonmuscle-invasive bladder cancer are immunotherapy, chemotherapy, or surgery.4 One common immunotherapy is injecting BCG, a harmless bacteria, directly into the bladder. It triggers an immune response that can fight the cancer, but it fails in 30-40% of cases, and even those who initially respond have a 50% chance of relapse within 2.5 years.1,2
Other drugs on the market, like Pembrolizumab, provide a possible solution, but its effectiveness is limited and comes with uncomfortable side effects. Partial or complete bladder removal surgery is a typical outcome, but it is a risky and drastic option, especially for the elderly who are most affected by nonmuscle-invasive bladder cancer.5 Depending on the type of procedure, patients face a whole range of different emotional and physical complications afterwards.6
Survival rate success
Historically, the prognosis for high-risk nonmuscle-invasive bladder cancer has been poor, with patients potentially progressing to more invasive disease or death.6 The success of ANKTIVA in boosting BCG efficacy in phase II and III clinical trials, however, may mark a turn towards a brighter future.
Dr. Karim Chamie, associate professor of urology at the David Geffen School of Medicine at UCLA, is optimistic about the future of nonmuscle-invasive bladder cancer treatments. By combining ANKTIVA with Bacillus Calmette-Guerin immunotherapy, 71% of patients experienced complete tumor disappearance for over two years, surpassing the original expectations set by experts. And most importantly, 89% of these patients avoided bladder surgery altogether.5
“While patients have had limited options in the past after failure of BCG, [ANKTIVA], with its reported safety and efficacy, now offers them yet another choice in their quest to avoid a radical cystectomy. This is a big win for [nonmuscle-invasive bladder cancer (NMIBC)] patients everywhere,” said Dr. Ashish Kamat, Professor of Urologic Oncology and Cancer Research at University of Texas MD Anderson Cancer Center in a recent press release.1
Flushing out the cancer
The team divided 171 patients into three groups to look at how different combinations of the new treatment would work in diverse types and stages of nonmuscle-invasive bladder cancer. They confirmed that all patients had already received and failed to respond to Bacillus Calmette-Guérin treatment. The drugs were given directly into the bladder using a urinary catheter. All patients received their treatments weekly for six consecutive weeks.
Group one patients had a specific type of nonmuscle-invasive bladder cancer, BCG-unresponsive carcinoma in situ (CIS) with or without Ta/T1 papillary disease, held within the inner lining of the bladder. It’s considered high-risk, because it can progress to more invasive cancer. They received ANKTIVA plus Bacillus Calmette-Guerin.
Group two patients had another, more advanced form of nonmuscle-invasive bladder cancer, BCG-unresponsive high-grade Ta/T1 papillary NMIBC, with tumors also highly likely to become invasive cancer. They also received ANKTIVA plus Bacillus Calmette-Guerin.
Group three patients had the same type of nonmuscle-invasive bladder cancer as group one, but they were only given ANKTIVA.
How did they check on their patients? They used a tube with a lens at the end of it, to insert and view inside the bladder and urethra, and they checked urine samples for any suspicious cells. They did this every three months for the first two years, and then every six months for five years. The researchers also took a bladder biopsy at three months and another one at six months. If they saw that a patient did not respond to initial treatment and did not have more advanced disease, then they offered them another round of treatment within the aforementioned time periods.
This study wasn’t just comprehensive, it was comprehensive-WIN-sive
The study measured 1) how many people in groups one and three had no cancer after treatment, and 2) how many people in group two lived without the cancer returning or worsening, and for how long.
In group one (bladder cancer, ANKTIVA plus BCG) 71% of patients experienced a “complete response.” This means their tumors completely disappeared after treatment during the 3-, 6-, and 12-month response assessments. This rate beat the 30% target considered clinically meaningful by experts. This treatment regime kept participants cancer free for a further two years. Eighty nine percent of group one patients avoided bladder removal surgery.
In group two (advanced bladder cancer, ANKTIVA plus Bacillus Calmette-Guerin) at the one-year mark, 100% of patients were alive, and at the two-year mark, 97% of patients were alive. At two years, 48% of patients were cancer free and 88% did not show any signs or symptoms of the cancer getting worse.
In group three (bladder cancer, ANKTIVA) only 10% of patients showed a “complete response” after treatment during the 3-, 6-, and 12-month response assessments, so the scientists decided to stop this treatment group.
Most side effects were mild to moderate and related to the bladder surgery procedure, with no evidence of systemic toxicity from the drug.
A wee step closer to curing bladder cancer
ANKTIVA isn’t a standalone treatment for nonmuscle-invasive bladder cancer. It’s designed to work in conjunction with Bacillus Calmette-Guerin (BCG), an existing immunotherapy. ANKTIVA boosts BCG’s effectiveness by priming the immune system to better target and destroy cancer cells.
The study results highlight this. Group 3 patients, who received ANKTIVA alone, had a very low response rate (10%). This indicates ANKTIVA doesn’t work effectively on its own. In contrast, Groups 1 and 2, who received ANKTIVA plus BCG, showed significantly better outcomes, demonstrating the synergistic effect of combining the two treatments.
The results of this study are promising. ANKTIVA plus Bacillus Calmette-Guerin works as a treatment for high-risk bladder cancer patients. This prompted them to expand on what this could treat. ANKTIVA is currently being studied in trials for other types of cancers, including lung, colorectal, and lymphoma.
Today, ANKTIVA is an FDA approved treatment for BCG-unresponsive non-muscle invasive bladder cancer and can soon be an option for patients everywhere.1
References
- Jhollister (2024) ImmunityBio announces FDA approval of Anktiva®, first-in-class IL-15 receptor agonist for BCG-unresponsive non-muscle invasive bladder cancer, ImmunityBio. Available at: https://immunitybio.com/immunitybio-announces-fda-approval-of-anktiva-first-in-class-il-15-receptor-agonist-for-bcg-unresponsive-non-muscle-invasive-bladder-cancer/ (Accessed: 07 June 2024).
- Zlotta AR, Fleshner NE, Jewett MA. The management of BCG failure in non-muscle-invasive bladder cancer: an update. Can Urol Assoc J. 2009 Dec;3(6 Suppl 4):S199-205. doi: 10.5489/cuaj.1196. PMID: 20019985; PMCID: PMC2792453.
- Key statistics for Bladder Cancer (no date) American Cancer Society. Available at: https://www.cancer.org/cancer/types/bladder-cancer/about/key-statistics.html#:~:text=time%20of%20diagnosis-,How%20common%20is%20bladder%20cancer%3F,men%20and%204%2C550%20in%20women (Accessed: 07 June 2024).
- Bladder cancer treatment (2023) Johns Hopkins Medicine. Available at: https://www.hopkinsmedicine.org/health/conditions-and-diseases/bladder-cancer/bladder-cancer-treatment (Accessed: 07 June 2024).
- Chamie, K. et al. (2023) ‘IL-15 superagonist NAI in BCG-unresponsive non–muscle-invasive bladder cancer’, NEJM Evidence, 2(1). doi:10.1056/evidoa2200167.
- Surgery to remove the bladder (cystectomy) (2023) Removing the bladder (cystectomy) for early bladder cancer | Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/bladder-cancer/treatment/invasive/surgery/removing-bladder (Accessed: 08 June 2024).
