U.S. Food and Drug Administration Approves Opdivo® (nivolumab), in Combination with Cisplatin and Gemcitabine, for First-Line Treatment of Adult Patients with Unresectable or Metastatic Urothelial Carcinoma
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Insights
The FDA's approval of Opdivo in combination with cisplatin and gemcitabine for the treatment of metastatic urothelial carcinoma is a significant development in the oncology field. The combination therapy has shown a 22% reduction in the risk of death and a 28% reduction in the risk of disease progression or death, which are substantial improvements over the standard chemotherapy regimen. From a clinical standpoint, these results could translate into a new standard of care for patients with this aggressive form of bladder cancer, potentially improving both survival rates and quality of life.
It is also worth noting that the use of immune checkpoint inhibitors like Opdivo, which work by enabling the immune system to recognize and attack cancer cells, has been expanding in oncology. This approval may encourage further research into combination therapies that include immunotherapy as a cornerstone for cancer treatment.
From a research analysis perspective, the CheckMate -901 trial's results are pivotal, as they support the broader application of immunotherapy in combination with chemotherapy. The trial's rigorous methodology and the use of Blinded Independent Central Review (BICR) for primary efficacy endpoints lend credibility to the findings. Furthermore, the trial's median follow-up of approximately 33 months provides a robust dataset for evaluating long-term outcomes.
Moreover, the approval process itself, which utilized the FDA's Real-Time Oncology Review (RTOR) pilot program and Project Orbis initiative, highlights a streamlined regulatory approach that could expedite the availability of new treatments in the future. This could potentially lead to faster adoption of new therapies in clinical practice, benefiting patients with time-sensitive conditions.
The approval of Opdivo for this new indication could have a significant impact on Bristol Myers Squibb's market position. As the first concurrent immunotherapy-chemotherapy combination approved for metastatic urothelial carcinoma, it may capture a substantial market share in this niche. The company's strategic portfolio expansion in genitourinary cancers, now spanning multiple stages and treatment needs, positions it well within the competitive landscape.
Investors should consider the potential for increased revenue streams from this approval, but also weigh the costs associated with marketing, production and potential post-market surveillance. It's also important to monitor the competitive environment, as other pharmaceutical companies may be incentivized to develop or improve their own combination therapies in response to Bristol Myers Squibb's success.
In the Phase 3 CheckMate -901 trial, Opdivo with cisplatin and gemcitabine demonstrated a statistically significant improvement in overall survival and progression-free survival compared to cisplatin-gemcitabine alone1
This is the first concurrent immunotherapy-chemotherapy combination approved for this patient population in the
In the trial, with a median follow-up of approximately 33 months, treatment with Opdivo in combination with cisplatin and gemcitabine reduced the risk of death by
Additionally, in exploratory analyses, treatment with Opdivo in combination with cisplatin and gemcitabine resulted in an objective response rate (ORR) of
“This approval marks an important advancement in a historically difficult-to-treat setting, where there has been a need for new and differentiated first-line approaches that may offer patients a chance to live longer,”5 said Guru P. Sonpavde, MD, Medical Director of Genitourinary Oncology and the Phase I Clinical Research Unit and Christopher K. Glanz Chair for Bladder Cancer Research at the AdventHealth Cancer Institute,
Opdivo is associated with the following Warnings & Precautions: severe and fatal immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials. Please see Important Safety Information below.1
“Bringing Opdivo to the first-line setting in UC with chemotherapy is the latest realization of our history of research and progress in immunotherapy, which has helped transform the treatment landscape for many cancers, including bladder cancer,”1,6 said Wendy Short Bartie, senior vice president and general manager,
The FDA previously approved Opdivo for the adjuvant treatment of adult patients with UC who are at high risk of recurrence after undergoing radical resection of UC; it also previously approved Opdivo for the treatment of adult patients with locally advanced or metastatic UC who have had disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.1
Bristol Myers Squibb’s supplemental Biologics License Application (sBLA) leading to today’s approval was granted Priority Review status by the FDA, and was approved under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.7 The review was also conducted under the FDA’s Project Orbis initiative, which enables concurrent review by the health authorities in several other countries where the application remains under review.
About CheckMate -901
CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy compared to cisplatin-gemcitabine alone, in patients with previously untreated unresectable or metastatic urothelial cancer.3
In the CheckMate -901 study, a total of 608 cisplatin-eligible patients were randomized to receive either Opdivo 360 mg in combination with cisplatin-gemcitabine every three weeks for up to six cycles followed by Opdivo monotherapy 480 mg every 4 weeks until disease progression or unacceptable toxicity up to a maximum of two years, or cisplatin-gemcitabine alone every three weeks for up to six cycles.1 The primary endpoints of this study were overall survival (OS) and progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR).1,3 The OS and PFS outcomes for cisplatin-eligible patients are based on the final efficacy analyses of these endpoints.4
Select Safety Profile from CheckMate -901
Serious adverse reactions occurred in
About Urothelial Carcinoma
Bladder cancer is the sixth most common cancer in the
INDICATION
OPDIVO® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma.
IMPORTANT SAFETY INFORMATION
Severe and Fatal Immune-Mediated Adverse Reactions
Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO. Early identification and management are essential to ensure safe use of OPDIVO. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment with OPDIVO. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue OPDIVO depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in
Immune-Mediated Hepatitis and Hepatotoxicity
OPDIVO can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in
Immune-Mediated Endocrinopathies
OPDIVO can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.
In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in
In patients receiving OPDIVO monotherapy, hypophysitis occurred in
In patients receiving OPDIVO monotherapy, thyroiditis occurred in
In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in
In patients receiving OPDIVO monotherapy, hypothyroidism occurred in
In patients receiving OPDIVO monotherapy, diabetes occurred in
Immune-Mediated Nephritis with Renal Dysfunction
OPDIVO can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in
Immune-Mediated Dermatologic Adverse Reactions
OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.
Withhold or permanently discontinue OPDIVO depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).
In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in
Other Immune-Mediated Adverse Reactions
The following clinically significant immune-mediated adverse reactions occurred at an incidence of <
Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, which has been observed in patients receiving OPDIVO, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.
Infusion-Related Reactions
OPDIVO can cause severe infusion-related reactions. Discontinue OPDIVO in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in
Complications of Allogeneic Hematopoietic Stem Cell Transplantation
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between OPDIVO and allogeneic HSCT.
Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO prior to or after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on its mechanism of action and findings from animal studies, OPDIVO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and for at least 5 months after the last dose.
Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone
In randomized clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.
Lactation
There are no data on the presence of OPDIVO in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 5 months after the last dose.
Serious Adverse Reactions
In Checkmate 901, serious adverse reactions occurred in
Common Adverse Reactions
In Checkmate 901, the most common adverse reactions (≥
Please see US Full Prescribing Information for OPDIVO.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Bristol Myers Squibb’s Patient Access Support
Bristol Myers Squibb remains committed to providing assistance so that cancer patients who need our medicines can access them and expedite time to therapy.
BMS Access Support®, the Bristol Myers Squibb patient access and reimbursement program, is designed to help appropriate patients initiate and maintain access to BMS medicines during their treatment journey. BMS Access Support offers benefit investigation, prior authorization assistance, as well as co-pay assistance for eligible, commercially insured patients. More information about our access and reimbursement support can be obtained by calling BMS Access Support at 1-800-861-0048 or by visiting www.bmsaccesssupport.com.
About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Cautionary Statement Regarding Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, whether Opdivo in combination with cisplatin and gemcitabine for the additional indication described in this release will be commercially successful, that any marketing approvals, if granted, may have significant limitations on their use, and, that continued approval of such combination treatment for such additional indication described in this release may be contingent upon verification and description of clinical benefit in confirmatory trials. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
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Opdivo Prescribing Information. Opdivo
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FAQ
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