The US Food and Drug Administration (FDA) has approved Opdivo, (nivolumab) for the treatment of patients with high risk early stage and locally advanced or metastatic urothelial carcinoma whose disease has progressed during a period of up to 1 year after first-line platinum-containing chemotherapy. Since approval clinical trials have continued to demonstrate that Opdivo delays recurrence and improves outcomes when used in earlier stage disease and in the adjuvant setting.1,2
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.
About Opdivo (nivolumab)
Opdivo is a type of immunotherapy called a Checkpoint inhibitor that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD -L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade an attack by the body’s immune cells. Checkpoint inhibitor drugs that block the PD-1 pathway enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the lung cancer cells.
Opdivo Doubles Disease-Free Survival in High-Risk Urothelial Carcinoma
Treatment with Opdivo® following surgery with or without cisplatin-based chemotherapy improve disease-free survival in patients with muscle-invasive urothelial carcinoma.
A trial evaluated the use of post-surgery (adjuvant) Opdivo in 709 patients with muscle-invasive urothelial carcinoma of the bladder, ureter, or renal pelvis who underwent radical surgery with or without pre-surgery (neoadjuvant) cisplatin-based chemotherapy. Patients with a high risk for recurrence based on the tumor stage at surgery were treated with either Opdivo or placebo every other week for 1 year and directly compared.
Opdivo treatment significantly delayed the time to cancer recurrence. Opdivo treated patients survived on average 21 months without cancer recurrence compared to only 11 months for those receiving placebo. The benefit from opdivo treatment was irrespective of PD-L1 status. In patients whose tumors had a PD-L1 expression of 1% or higher Opdivo immunotherapy resulted in a 45% reduction in the risk of disease recurrence or death
Concurrent Opdivo and gemcitabine/cisplatin (GC) followed by Opdivo maintenance therapy has also been reported to prolong survival and delays cancer recurrence when compared to GC chemotherapy alone in patients with previously untreated, metastatic or unresectable urothelial carcinoma. According to findings from the phase 3 CheckMate 901 clinical trial (NCT03036098) presented at the ESMO Congress in October 2023 the 12 and 24-month survival rates with the Opdivo combination were 70% and 47%, compared with 63% and 41%, respectively, with GC alone.3
Overall opdivo therapy has been reported to be well tolerated, and the most common treatment-related side effects were diarrhea, colitis, and pneumonitis.
Opdivo is the first immune therapy to be used in the adjuvant setting that provides clinically meaningful improvement in disease-free survival for patients with high-risk muscle-invasive urothelial carcinoma after radical surgery with curative intent. This trial led to FDA approval of Opdivo for use as adjuvant treatment of patients with urothelial carcinoma who are at high risk of cancer recurrence after undergoing surgical removal of their cancer in August 2021.
Approval in Advanced Disease
The programmed cell death receptor–1 inhibitor Opdivo was the second immunotherapy drug approved to treat advanced bladder cancer. The FDA also approved Tecentriq (atezolizumab), which acts as a programmed cell death ligand–1 inhibitor, in May 2016.
On March 6, 2024, the FDA approved Opdivo in combination with cisplatin and gemcitabine chemotherapy for first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC) based on results from the CHECKMATE-901 clinical trial which evaluated the addition of Opdivo to gemcitabine-cisplatin chemotherapy in 608 patients with previously untreated unresectable or metastatic UC. The addition of Opdivo modestly improved the median overall survival duration from 18.9 to 21.7 months.
An approval for second line treatment was based on a study in 270 patients with locally advanced or metastatic urothelial carcinoma who experienced disease progression during or following platinum-containing chemotherapy, or whose disease progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
The objective response rate following Opdivo treatment was 19.6%; 7 patients had complete responses, and 46 had partial responses. The estimated median duration of response was 10.3 months. The FDA notes that some responses were ongoing at data cutoff.
The most common side effects from treatment were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritis.
Connect With Others for Support and information
Cancer Connect was the first social network created for people with bladder cancer. Founded by oncologists to support cancer patients and their caregivers, over 40 million individuals have accessed Cancer Connect programs since 1997. Cancer Connect is used by leading cancer centers like Dana Farber, Roswell Park and The James at Ohio State to support their patients. Join the conversation, ask questions, share your experience, and learn how the best cancer centers are treating cancer from others. Share your experience, ask a question, or start a conversation by posting on Cancer Connect.
Reference:
- Nivolumab for Treatment of Urothelial Carcinoma
- First results from the phase 3 CheckMate 274 trial of adjuvant nivolumab vs placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma (MIUC).
- van der Heijden MS, Sonpavde G, Powles T, et al. Nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone for previously untreated unresectable or metastatic urothelial carcinoma: Results from the phase III CheckMate 901 trial. Presented at: ESMO Congress 2023; October 20-24, 2023; Madrid, Spain. Abstract LBA7.
