Opdivo in combination with chemotherapy and Opdivo plus Yervoy® (ipilimumab) approved based on a Phase 3 trial showing improved overall survival versus chemotherapy alone1,2
Opdivo-based treatments are now approved for five indications in upper gastroesophageal cancers1
PRINCETON, NJ, USA I May 27, 2022 I Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has approved both Opdivo® (nivolumab) (injection for intravenous use) in combination with fluoropyrimidine- and platinum-containing chemotherapy and Opdivo® plus Yervoy® (ipilimumab) as a first-line treatment for adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) regardless of PD-L1 status. The approvals are based on the Phase 3 CheckMate -648 trial, which evaluated Opdivo in combination with chemotherapy (n=321) and Opdivo plus Yervoy (n=325) each compared to chemotherapy alone (n=324), and was the largest Phase 3 trial of an immunotherapy in first-line ESCC.1
In the trial, Opdivo in combination with chemotherapy demonstrated superior overall survival (OS) compared to chemotherapy alone, both in all randomized patients, a secondary endpoint, which was hierarchically tested (Hazard Ratio [HR] 0.74, 95% Confidence Interval [CI]: 0.61 to 0.90, P=0.0021) and in patients whose tumors express PD-L1 (≥1%), a primary endpoint (HR 0.54, 95% CI: 0.41 to 0.71, P<0.0001).1,2 In all randomized patients the median OS (mOS) was 13.2 months (95% CI: 11.1 to 15.7) with Opdivo in combination with chemotherapy versus 10.7 months (95% CI: 9.4 to 11.9) with chemotherapy alone.1 In patients whose tumors express PD-L1 (≥1%) the mOS was 15.4 months (95% CI: 11.9 to 19.5) for Opdivo in combination with chemotherapy versus 9.1 months (95% CI: 7.7 to 10) with chemotherapy alone.1 The median progression-free survival (PFS) in all randomized patients, which was a hierarchically tested secondary endpoint, was 5.8 months (95% CI: 5.6 to 7.0) for Opdivo in combination with chemotherapy and 5.6 months (95% CI: 4.3 to 5.9) for chemotherapy alone (HR= 0.81; 95% CI: 0.67 to 0.99, P=not significant). Per pre-specified analysis, PFS did not meet statistical significance.1 The median PFS in patients whose tumors express PD-L1 (≥1%), which was a co-primary endpoint, was 6.9 months (95% CI: 5.7 to 8.3) for Opdivo in combination with chemotherapy and 4.4 months (95% CI: 2.9 to 5.8) for chemotherapy alone (HR 0.65; 95% CI: 0.49 to 0.86, P=0.0023).1
Opdivo plus Yervoy also improved OS compared to chemotherapy in all-randomized patients, a secondary endpoint, which was hierarchically tested (HR 0.78, 95% CI: 0.65 to 0.95, P=0.0110) and patients whose tumors express PD-L1 (≥1%), a primary endpoint (HR 0.64, 95% CI: 0.49 to 0.84, P=0.0010).1,2 The mOS was 12.8 months (95% CI: 11.3 to 15.5) with Opdivo plus Yervoy versus 10.7 months (95% CI: 9.4 to 11.9) with chemotherapy alone in all randomized patients and 13.7 months (95% CI: 11.2 to 17.0) with Opdivo plus Yervoy versus 9.1 months (95% CI: 7.7 to 10) with chemotherapy alone in patients whose tumors express PD-L1 (≥1%).1 The median PFS in patients whose tumors express PD-L1 (≥1%), which was a co-primary endpoint, was 4.0 months (95% CI: 2.4 to 4.9) for Opdivo plus Yervoy and 4.4 months (95% CI: 2.9 to 5.8) for chemotherapy alone (HR 1.02; 95% CI: 0.78 to 1.34, P=not significant). Per pre-specified analysis, PFS did not meet statistical significance.1,2 Median PFS in the PD-L1 (≥1%) population was not statistically significant and therefore it was not hierarchically tested in the all comers population.
Opdivo alone and Opdivo plus Yervoy are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis and renal dysfunction, dermatologic adverse reactions, 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.1 Please see the Important Safety Information section below.
“Today brings welcome news for many advanced or metastatic esophageal squamous cell carcinoma patients and oncologists,” said Jaffer A. Ajani, M.D., CheckMate -648 co-first author and lead U.S. investigator, and professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. “Unresectable advanced or metastatic esophageal squamous cell carcinoma is a challenging disease, and there’s a need for additional treatment options that may extend survival in the first-line setting.3,4 In the CheckMate -648 trial, two nivolumab-based combinations showed a survival benefit compared to chemotherapy alone, offering new treatment options regardless of PD-L1 status.”1
This application was reviewed 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.5
“At Bristol Myers Squibb, we recognize the need that exists for many patients facing upper gastroesophageal cancers, including advanced or metastatic esophageal squamous cell carcinoma, and we are focused on our goal to bring forward new treatment options with proven survival benefits regardless of PD-L1 status and histology,” said Adam Lenkowsky, senior vice president and general manager, U.S., Cardiovascular, Immunology, Oncology, Bristol Myers Squibb.6 “Today’s approvals bring two first-line immunotherapy-based treatment options at once, Opdivo in combination with chemotherapy and Opdivo plus Yervoy as the first dual immunotherapy option, to newly diagnosed patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, further building on the role of Opdivo-based regimens in upper gastroesophageal cancers.”1
About CheckMate -648
CheckMate -648 is a randomized Phase 3 study evaluating Opdivo plus Yervoy or Opdivo in combination with chemotherapy (fluorouracil and cisplatin) against chemotherapy (fluorouracil plus cisplatin) alone in adult patients with previously untreated unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma.1,2 The primary endpoints of the trial are overall survival (OS) and progression-free survival (PFS) determined by blinded independent central review (BICR) in patients whose tumors express PD-L1 (≥1%) for both Opdivo-based combinations versus chemotherapy.2 Secondary endpoints of the trial, including OS and PFS as determined by BICR in the all randomized population, were tested hierarchically only if corresponding primary endpoints were significant.1,2
In the Opdivo plus Yervoy arm, patients received treatment with Opdivo 3 mg/kg every 2 weeks and Yervoy 1 mg/kg every 6 weeks up to 2 years or until disease progression or unacceptable toxicity.1,2 In the Opdivo in combination with chemotherapy arm, patients received treatment with Opdivo 240 mg on Day 1 and Day 15, fluorouracil 800 mg/m²/day on Day 1 through Day 5 for five days, and cisplatin 80 mg/m² on Day 1 of a four-week cycle.1,2 Patients were treated with Opdivo until disease progression, unacceptable toxicity, or up to 2 years.1,2 In patients who received Opdivo in combination with chemotherapy and in whom either fluorouracil and/or cisplatin were discontinued, other components of the treatment regimen were allowed to be continued. 2 Patients who discontinued combination therapy because of an adverse reaction attributed to ipilimumab were permitted to continue Opdivo as a single agent.2
Select Safety Profile from CheckMate -648 Study
Opdivo and/or chemotherapy were discontinued in 39% of patients and were delayed in 71% of patients for an adverse reaction.1 Serious adverse reactions occurred in 62% of patients receiving Opdivo in combination with chemotherapy.1 The most frequent (≥2%) serious adverse reactions in patients receiving Opdivo in combination with chemotherapy were pneumonia (11%), dysphagia (7%), esophageal stenosis (2.9%), acute kidney injury (2.9%), and pyrexia (2.3%).1 Fatal adverse reactions occurred in 5 (1.6%) patients treated with Opdivo in combination with chemotherapy; these included pneumonitis, pneumatosis intestinalis, pneumonia, and acute kidney injury.1 The most common (≥20%) adverse reactions in patients treated with Opdivo in combination with chemotherapy were nausea (65%), decreased appetite (51%), fatigue (47%), constipation (44%), stomatitis (44%), diarrhea (29%), and vomiting (23%).1
Opdivo and/or Yervoy were discontinued in 23% of patients and were delayed in 46% of patients for an adverse reaction.1 Serious adverse reactions occurred in 69% of patients receiving Opdivo plus Yervoy.1 The most frequent (≥2%) serious adverse reactions in patients receiving Opdivo plus Yervoy were pneumonia (10%), pyrexia (4.3%), pneumonitis (4%), aspiration pneumonia (3.7%), dysphagia (3.7%), hepatic function abnormal (2.8%), decreased appetite (2.8%), adrenal insufficiency (2.5%), and dehydration (2.5%).1 Fatal adverse reactions occurred in 5 (1.6%) patients treated with Opdivo plus Yervoy; these included pneumonitis, interstitial lung disease, pulmonary embolism, and acute respiratory distress syndrome.1 The most common (≥20%) adverse reactions in patients treated with Opdivo plus Yervoy were rash (31%), fatigue (28%), pyrexia (23%), nausea (22%), diarrhea (22%), and constipation (20%).1
About Esophageal Cancer
In the United States, it is estimated that approximately 20,640 new cases of esophageal cancer will be diagnosed and approximately 16,410 deaths will result from the disease in 2022 alone.7 Esophageal cancer, which can impact the patient’s ability to swallow and eat, is a type of gastroesophageal cancer that starts in the inner layer of the esophagus (the mucosa) and grows.8,9 The mucosa is normally lined with squamous cells.9 Cancer starting in these cells is called squamous cell carcinoma, which is most often found in the upper and middle part of the esophagus, and accounts for less than 30% of esophageal cancers in the United States.9 For about 39% of patients, esophageal cancer is diagnosed in the advanced stage, which is typically harder to treat.10
INDICATIONS
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with ipilimumab, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
Please see US Full Prescribing Information for OPDIVO and YERVOY.
Clinical Trials and Patient Populations
Attraction-3—esophageal squamous cell carcinoma; Checkmate 577—adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 648—previously untreated, unresectable advanced, metastatic esophageal squamous cell carcinoma in combination with fluoropyrimidine- and platinum-containing chemotherapy; Checkmate 648—previously untreated, unresectable advanced, or metastatic esophageal squamous cell carcinoma, in combination with YERVOY; Checkmate 649—previously untreated advanced or metastatic gastric or gastroesophageal junction or esophageal adenocarcinoma
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 scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at 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. Because 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 Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
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.
Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.
References
- Opdivo Prescribing Information. Opdivo U.S. Product Information. Last updated: May 2022. Princeton, NJ: Bristol-Myers Squibb Company.
- Chau I, Doki Y, Ajani JA, et al. Nivolumab plus Ipilimumab or Nivolumab plus Chemotherapy versus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma: First Results of the CheckMate 648 study. Poster presented at: 2021 American Society of Clinical Oncology (ASCO) Virtual Congress. June 4-8, 2021.
- American Cancer Society. Treating Esophageal Cancer by Stage. https://www.cancer.org/cancer/esophagus-cancer/treating/by-stage.html. Updated May 21, 2021. Accessed April 7, 2022.
- Dahiya DS, Kichloo A, Singh J, et al. Current Immunotherapy in Gastrointestinal Malignancies A Review. J Investig Med. 2021;69:689-696.
- U.S. Food & Drug Administration. Real-Time Oncology Review Pilot Program. https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review. Updated March 10, 2022. Accessed May 24, 2022.
- Myint ZW, Goel G. Role of Modern Immunotherapy in Gastrointestinal Malignancies: a Review of Current Clinical Progress. J Hematol Oncol. 2017 Apr 24;10(1):86.
- American Cancer Society. Key Statistics for Esophageal Cancer. https://www.cancer.org/cancer/esophagus-cancer/about/key-statistics.html. Updated January 12, 2022. Accessed May 24, 2022.
- PDQ® Adult Treatment Editorial Board. PDQ Esophageal Cancer Treatment (Adult). https://www.cancer.gov/types/esophageal/patient/esophageal-treatment-pdq. Last updated: November 18, 2021. Accessed May 24, 2022. Bethesda, MD: National Cancer Institute.
- American Cancer Society. What Is Cancer of the Esophagus? https://www.cancer.org/cancer/esophagus-cancer/about/what-is-cancer-of-the-esophagus.html. Updated March 20, 2020. Accessed May 24, 2022.
- SEER. Cancer Stat Facts: Esophageal Cancer. https://seer.cancer.gov/statfacts/html/esoph.html. Accessed May 24, 2022.
SOURCE: Bristol Myers Squibb
Post Views: 51
Opdivo in combination with chemotherapy and Opdivo plus Yervoy® (ipilimumab) approved based on a Phase 3 trial showing improved overall survival versus chemotherapy alone1,2
Opdivo-based treatments are now approved for five indications in upper gastroesophageal cancers1
PRINCETON, NJ, USA I May 27, 2022 I Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has approved both Opdivo® (nivolumab) (injection for intravenous use) in combination with fluoropyrimidine- and platinum-containing chemotherapy and Opdivo® plus Yervoy® (ipilimumab) as a first-line treatment for adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) regardless of PD-L1 status. The approvals are based on the Phase 3 CheckMate -648 trial, which evaluated Opdivo in combination with chemotherapy (n=321) and Opdivo plus Yervoy (n=325) each compared to chemotherapy alone (n=324), and was the largest Phase 3 trial of an immunotherapy in first-line ESCC.1
In the trial, Opdivo in combination with chemotherapy demonstrated superior overall survival (OS) compared to chemotherapy alone, both in all randomized patients, a secondary endpoint, which was hierarchically tested (Hazard Ratio [HR] 0.74, 95% Confidence Interval [CI]: 0.61 to 0.90, P=0.0021) and in patients whose tumors express PD-L1 (≥1%), a primary endpoint (HR 0.54, 95% CI: 0.41 to 0.71, P<0.0001).1,2 In all randomized patients the median OS (mOS) was 13.2 months (95% CI: 11.1 to 15.7) with Opdivo in combination with chemotherapy versus 10.7 months (95% CI: 9.4 to 11.9) with chemotherapy alone.1 In patients whose tumors express PD-L1 (≥1%) the mOS was 15.4 months (95% CI: 11.9 to 19.5) for Opdivo in combination with chemotherapy versus 9.1 months (95% CI: 7.7 to 10) with chemotherapy alone.1 The median progression-free survival (PFS) in all randomized patients, which was a hierarchically tested secondary endpoint, was 5.8 months (95% CI: 5.6 to 7.0) for Opdivo in combination with chemotherapy and 5.6 months (95% CI: 4.3 to 5.9) for chemotherapy alone (HR= 0.81; 95% CI: 0.67 to 0.99, P=not significant). Per pre-specified analysis, PFS did not meet statistical significance.1 The median PFS in patients whose tumors express PD-L1 (≥1%), which was a co-primary endpoint, was 6.9 months (95% CI: 5.7 to 8.3) for Opdivo in combination with chemotherapy and 4.4 months (95% CI: 2.9 to 5.8) for chemotherapy alone (HR 0.65; 95% CI: 0.49 to 0.86, P=0.0023).1
Opdivo plus Yervoy also improved OS compared to chemotherapy in all-randomized patients, a secondary endpoint, which was hierarchically tested (HR 0.78, 95% CI: 0.65 to 0.95, P=0.0110) and patients whose tumors express PD-L1 (≥1%), a primary endpoint (HR 0.64, 95% CI: 0.49 to 0.84, P=0.0010).1,2 The mOS was 12.8 months (95% CI: 11.3 to 15.5) with Opdivo plus Yervoy versus 10.7 months (95% CI: 9.4 to 11.9) with chemotherapy alone in all randomized patients and 13.7 months (95% CI: 11.2 to 17.0) with Opdivo plus Yervoy versus 9.1 months (95% CI: 7.7 to 10) with chemotherapy alone in patients whose tumors express PD-L1 (≥1%).1 The median PFS in patients whose tumors express PD-L1 (≥1%), which was a co-primary endpoint, was 4.0 months (95% CI: 2.4 to 4.9) for Opdivo plus Yervoy and 4.4 months (95% CI: 2.9 to 5.8) for chemotherapy alone (HR 1.02; 95% CI: 0.78 to 1.34, P=not significant). Per pre-specified analysis, PFS did not meet statistical significance.1,2 Median PFS in the PD-L1 (≥1%) population was not statistically significant and therefore it was not hierarchically tested in the all comers population.
Opdivo alone and Opdivo plus Yervoy are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis and renal dysfunction, dermatologic adverse reactions, 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.1 Please see the Important Safety Information section below.
“Today brings welcome news for many advanced or metastatic esophageal squamous cell carcinoma patients and oncologists,” said Jaffer A. Ajani, M.D., CheckMate -648 co-first author and lead U.S. investigator, and professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. “Unresectable advanced or metastatic esophageal squamous cell carcinoma is a challenging disease, and there’s a need for additional treatment options that may extend survival in the first-line setting.3,4 In the CheckMate -648 trial, two nivolumab-based combinations showed a survival benefit compared to chemotherapy alone, offering new treatment options regardless of PD-L1 status.”1
This application was reviewed 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.5
“At Bristol Myers Squibb, we recognize the need that exists for many patients facing upper gastroesophageal cancers, including advanced or metastatic esophageal squamous cell carcinoma, and we are focused on our goal to bring forward new treatment options with proven survival benefits regardless of PD-L1 status and histology,” said Adam Lenkowsky, senior vice president and general manager, U.S., Cardiovascular, Immunology, Oncology, Bristol Myers Squibb.6 “Today’s approvals bring two first-line immunotherapy-based treatment options at once, Opdivo in combination with chemotherapy and Opdivo plus Yervoy as the first dual immunotherapy option, to newly diagnosed patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, further building on the role of Opdivo-based regimens in upper gastroesophageal cancers.”1
About CheckMate -648
CheckMate -648 is a randomized Phase 3 study evaluating Opdivo plus Yervoy or Opdivo in combination with chemotherapy (fluorouracil and cisplatin) against chemotherapy (fluorouracil plus cisplatin) alone in adult patients with previously untreated unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma.1,2 The primary endpoints of the trial are overall survival (OS) and progression-free survival (PFS) determined by blinded independent central review (BICR) in patients whose tumors express PD-L1 (≥1%) for both Opdivo-based combinations versus chemotherapy.2 Secondary endpoints of the trial, including OS and PFS as determined by BICR in the all randomized population, were tested hierarchically only if corresponding primary endpoints were significant.1,2
In the Opdivo plus Yervoy arm, patients received treatment with Opdivo 3 mg/kg every 2 weeks and Yervoy 1 mg/kg every 6 weeks up to 2 years or until disease progression or unacceptable toxicity.1,2 In the Opdivo in combination with chemotherapy arm, patients received treatment with Opdivo 240 mg on Day 1 and Day 15, fluorouracil 800 mg/m²/day on Day 1 through Day 5 for five days, and cisplatin 80 mg/m² on Day 1 of a four-week cycle.1,2 Patients were treated with Opdivo until disease progression, unacceptable toxicity, or up to 2 years.1,2 In patients who received Opdivo in combination with chemotherapy and in whom either fluorouracil and/or cisplatin were discontinued, other components of the treatment regimen were allowed to be continued. 2 Patients who discontinued combination therapy because of an adverse reaction attributed to ipilimumab were permitted to continue Opdivo as a single agent.2
Select Safety Profile from CheckMate -648 Study
Opdivo and/or chemotherapy were discontinued in 39% of patients and were delayed in 71% of patients for an adverse reaction.1 Serious adverse reactions occurred in 62% of patients receiving Opdivo in combination with chemotherapy.1 The most frequent (≥2%) serious adverse reactions in patients receiving Opdivo in combination with chemotherapy were pneumonia (11%), dysphagia (7%), esophageal stenosis (2.9%), acute kidney injury (2.9%), and pyrexia (2.3%).1 Fatal adverse reactions occurred in 5 (1.6%) patients treated with Opdivo in combination with chemotherapy; these included pneumonitis, pneumatosis intestinalis, pneumonia, and acute kidney injury.1 The most common (≥20%) adverse reactions in patients treated with Opdivo in combination with chemotherapy were nausea (65%), decreased appetite (51%), fatigue (47%), constipation (44%), stomatitis (44%), diarrhea (29%), and vomiting (23%).1
Opdivo and/or Yervoy were discontinued in 23% of patients and were delayed in 46% of patients for an adverse reaction.1 Serious adverse reactions occurred in 69% of patients receiving Opdivo plus Yervoy.1 The most frequent (≥2%) serious adverse reactions in patients receiving Opdivo plus Yervoy were pneumonia (10%), pyrexia (4.3%), pneumonitis (4%), aspiration pneumonia (3.7%), dysphagia (3.7%), hepatic function abnormal (2.8%), decreased appetite (2.8%), adrenal insufficiency (2.5%), and dehydration (2.5%).1 Fatal adverse reactions occurred in 5 (1.6%) patients treated with Opdivo plus Yervoy; these included pneumonitis, interstitial lung disease, pulmonary embolism, and acute respiratory distress syndrome.1 The most common (≥20%) adverse reactions in patients treated with Opdivo plus Yervoy were rash (31%), fatigue (28%), pyrexia (23%), nausea (22%), diarrhea (22%), and constipation (20%).1
About Esophageal Cancer
In the United States, it is estimated that approximately 20,640 new cases of esophageal cancer will be diagnosed and approximately 16,410 deaths will result from the disease in 2022 alone.7 Esophageal cancer, which can impact the patient’s ability to swallow and eat, is a type of gastroesophageal cancer that starts in the inner layer of the esophagus (the mucosa) and grows.8,9 The mucosa is normally lined with squamous cells.9 Cancer starting in these cells is called squamous cell carcinoma, which is most often found in the upper and middle part of the esophagus, and accounts for less than 30% of esophageal cancers in the United States.9 For about 39% of patients, esophageal cancer is diagnosed in the advanced stage, which is typically harder to treat.10
INDICATIONS
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with ipilimumab, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
Please see US Full Prescribing Information for OPDIVO and YERVOY.
Clinical Trials and Patient Populations
Attraction-3—esophageal squamous cell carcinoma; Checkmate 577—adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 648—previously untreated, unresectable advanced, metastatic esophageal squamous cell carcinoma in combination with fluoropyrimidine- and platinum-containing chemotherapy; Checkmate 648—previously untreated, unresectable advanced, or metastatic esophageal squamous cell carcinoma, in combination with YERVOY; Checkmate 649—previously untreated advanced or metastatic gastric or gastroesophageal junction or esophageal adenocarcinoma
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 scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at 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. Because 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 Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
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.
Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.
References
- Opdivo Prescribing Information. Opdivo U.S. Product Information. Last updated: May 2022. Princeton, NJ: Bristol-Myers Squibb Company.
- Chau I, Doki Y, Ajani JA, et al. Nivolumab plus Ipilimumab or Nivolumab plus Chemotherapy versus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma: First Results of the CheckMate 648 study. Poster presented at: 2021 American Society of Clinical Oncology (ASCO) Virtual Congress. June 4-8, 2021.
- American Cancer Society. Treating Esophageal Cancer by Stage. https://www.cancer.org/cancer/esophagus-cancer/treating/by-stage.html. Updated May 21, 2021. Accessed April 7, 2022.
- Dahiya DS, Kichloo A, Singh J, et al. Current Immunotherapy in Gastrointestinal Malignancies A Review. J Investig Med. 2021;69:689-696.
- U.S. Food & Drug Administration. Real-Time Oncology Review Pilot Program. https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review. Updated March 10, 2022. Accessed May 24, 2022.
- Myint ZW, Goel G. Role of Modern Immunotherapy in Gastrointestinal Malignancies: a Review of Current Clinical Progress. J Hematol Oncol. 2017 Apr 24;10(1):86.
- American Cancer Society. Key Statistics for Esophageal Cancer. https://www.cancer.org/cancer/esophagus-cancer/about/key-statistics.html. Updated January 12, 2022. Accessed May 24, 2022.
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SOURCE: Bristol Myers Squibb
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