U.S. Food and Drug Administration Approves Opdivo®(nivolumab) in Combination with Chemotherapy for Patients with Advanced or Metastatic Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma
In the trial of this patient population, Opdivo plus chemotherapy demonstrated superior overall survival (OS) compared to chemotherapy alone, both in all randomized patients (OS HR 0.80; 95% CI: 0.71 to 0.90; P=0.0002), as well as in patients with PD-L1 combined positive score (CPS) ≥ 5 (OS HR 0.71; 95% CI: 0.61 to 0.83; P<0.0001).1 In an exploratory analysis of all patients, 55% of patients on Opdivoin combination with chemotherapy were alive at one year versus 48% of patients on chemotherapy alone.2 The combination also significantly reduced the risk of disease progression or death compared to chemotherapy alone (PD-L1 CPS ≥ 5: progression-free survival (PFS) HR 0.68; 95% CI: 0.58 to 0.79; P<0.0001).1
“In CheckMate -649, Opdivo plus chemotherapy combination significantly improved survival for patients with metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, reducing the risk of death by 20%.1 Additionally, 55% of patients were still alive at one year,” said Yelena Y. Janjigian, M.D., CheckMate -649 principal investigator and chief of gastrointestinal oncology, Memorial Sloan Kettering Cancer Center.2 “These findings are important, reinforcing the potential of this Opdivo-based combination as a standard of care for this population of patients in high need of treatment options that may extend their lives.”1,3,4
Opdivo is 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, as well as select safety information from CheckMate -649.
“We are focused on bringing transformative medicines to patients in need, and historically, there has been little progress for patients diagnosed with these metastatic gastroesophageal adenocarcinomas,” said Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, Bristol Myers Squibb.5,6,7,8 “As demonstrated in the CheckMate -649 trial, Opdivo is the first and only immunotherapy combined with chemotherapy to deliver superior overall survival versus chemotherapy alone in first-line metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.1,3,4 Today’s approval may offer these patients hope for the chance at a longer life.”1
The 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.9The review was also conducted under the FDA’s Project Orbis initiative, enabling concurrent review by the health authorities in Canada, Australia, Switzerland and Brazil.
Disclosure: Dr. Janjigian has provided advisory and speaking services to Bristol Myers Squibb.
About CheckMate -649
CheckMate -649 is a randomized, multicenter, open-label Phase 3 trial in patients with previously untreated advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.1,2 The trial excluded patients who were known human epidermal growth factor receptor 2 (HER2) positive, or had untreated CNS metastases.1 In the trial, patients were randomized to receive Opdivo in combination with chemotherapy (patients with PD-L1 CPS ≥ 5: n=473; all randomized patients: n=789) or chemotherapy alone (patients with PD-L1 CPS ≥ 5: n=482; all randomized patients: n=792).1 Patients received one of the following treatments: Opdivo 240 mg in combination with mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) every two weeks or mFOLFOX6 every two weeks; or Opdivo 360 mg in combination with CapeOX (capecitabine and oxaliplatin) every three weeks or CapeOX every three weeks.1 Patients were treated until disease progression, unacceptable toxicity, or up to two years.1 The primary endpoints, assessed in patients with PD-L1 CPS ≥ 5, were PFS assessed by Blinded Independent Central Review (BICR) and OS.1 Secondary endpoints included OS and PFS in patients with PD-L1 CPS ≥1 and in all randomized patients, and overall response rate (ORR) as assessed by BICR in patients with PD-L1 CPS ≥ 1 and ≥ 5, and in all randomized patients.1,2
The FDA-approved dosing for Opdivo (injection for intravenous use) for patients with gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma is 360 mg every three weeks (30-minute intravenous infusion) with fluoropyrimidine- and platinum-containing chemotherapy every three weeks or 240 mg every two weeks (30-minute intravenous infusion) with fluoropyrimidine- and platinum-containing chemotherapy every two weeks until disease progression, unacceptable toxicity, or up to two years.1
Select Safety Profile from CheckMate -649 Study
Opdivo and/or chemotherapy were discontinued in 44% of patients and at least one dose was withheld in 76% of patients due to an adverse reaction.1 Serious adverse reactions occurred in 52% of patients treated with Opdivo in combination with chemotherapy.1 The most frequent serious adverse reactions reported in ≥ 2% of patients treated with Opdivo in combination with chemotherapy were vomiting (3.7%), pneumonia (3.6%), anemia (3.6%), pyrexia (2.8%), diarrhea (2.7%), febrile neutropenia (2.6%), and pneumonitis (2.4%).1 Fatal adverse reactions occurred in 16 (2.0%) patients who were treated with Opdivo in combination with chemotherapy.1 The most common adverse reactions reported in ≥20% of patients treated with Opdivo in combination with chemotherapy were peripheral neuropathy (53%), nausea (48%), fatigue (44%), diarrhea (39%), vomiting (31%), decreased appetite (29%), abdominal pain (27%), constipation (25%), and musculoskeletal pain (20%).1
About Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma
Gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma are classified as upper gastrointestinal cancers.10,11
- Gastric cancer, also known as stomach cancer, is estimated to affect approximately 26,560 people in the United States in 2021 with 11,180 estimated deaths.11,12 Approximately 90-95% of all gastric cancers are adenocarcinomas.11 Currently, the five-year relative survival rate for metastatic gastric cancer is 6% in the United States.13,14
- The gastroesophageal junction (GEJ) is the area of the body that connects the lower part of the esophagus to the stomach.11 The prevalence of GEJ cancer has continued to rise.6,15 Adenocarcinomas that start at the gastroesophageal junction tend to behave similarly to esophageal cancers and are treated like them, as well.10
- Esophageal cancer is a type of gastrointestinal cancer that starts in the inner layer of the esophagus (the mucosa) and grows.10 In the United States, it is estimated there will be approximately 19,260 new cases of esophageal cancer diagnosed and 15,530 deaths resulted from the disease in 2021.16 The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma.16 The five-year relative survival rate for metastatic esophageal cancer is 5% in the United States.17,18
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
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.
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 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%).
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 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%).
Immune-Mediated Hepatitis and Hepatotoxicity
OPDIVO can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%).
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 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%).
In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%).
In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%).
In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%).
In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%).
In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis.
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 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%).
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 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%).
Other Immune-Mediated Adverse Reactions
The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO monotherapy or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system:meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; ocular:uveitis, iritis, and other ocular inflammatory toxicities can occur; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine: hypoparathyroidism; other (hematologic/immune):hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.
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.
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 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO.
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.
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.
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 649, serious adverse reactions occurred in 52% of patients treated with OPDIVO in combination with chemotherapy (n=782). The most frequent serious adverse reactions reported in ≥ 2% of patients treated with OPDIVO in combination with chemotherapy were vomiting (3.7%), pneumonia (3.6%), anemia, (3.6%), pyrexia (2.8%), diarrhea (2.7%), febrile neutropenia (2.6%), and pneumonitis (2.4%). Fatal adverse reactions occurred in 16 (2.0%) patients who were treated with OPDIVO in combination with chemotherapy; these included pneumonitis (4 patients), febrile neutropenia (2 patients), stroke (2 patients), gastrointestinal toxicity, intestinal mucositis, septic shock, pneumonia, infection, gastrointestinal bleeding, mesenteric vessel thrombosis, and disseminated intravascular coagulation.
Common Adverse Reactions
In Checkmate 649, the most common adverse reactions (≥20%) in patients treated with OPDIVO in combination with chemotherapy (n=782) were peripheral neuropathy (53%), nausea (48%), fatigue (44%), diarrhea (39%), vomiting (31%), decreased appetite (29%), abdominal pain (27%), constipation (25%), and musculoskeletal pain (20%).
Please see U.S. 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 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 Bristol Myers Squibb 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, Facebookand 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.
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 historical performance and 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 chemotherapy for the additional indication described in this release will be commercially successful 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, 2020, 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.
Opdivo Prescribing Information. Opdivo U.S. Product Information. Last updated: April 2021. Princeton, NJ: Bristol-Myers Squibb Company.
Moehler M, Shitara K, Garrido M, et al. Nivolumab plus chemotherapy versus chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma: first results of the CheckMate 649 study. Late-breaker presented at: 2020 European Society for Medical Oncology (ESMO) Virtual Congress. September 19-21, 2020.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines: Gastric Cancer. https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf. Updated February 9,2021. Accessed March 5, 2021.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines: Esophageal and Esophagogastric Junction Cancers. https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf. Updated February 9, 2021. Accessed March 5, 2021.
Samson P and Lockhart AC. Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. J Gastrointest Oncol. 2017;8(3):418-429.
Murphy AG, Lynch D and Kelly RJ. State of the art management of metastatic gastroesophageal cancer. Ann Transl Med. 2015;3(16):236.
Ai D, Zhu H, Ren W, et al. Patterns of distant organ metastases in esophageal cancer: a population-based study. J Thorac Dis. 2017;9(9):3023-3030.
Nagaraja AK, Kikuchi O and Bass AJ. Genomics and targeted therapies in gastroesophageal adenocarcinoma. Cancer Discov. 2019;9(12):1656-1672.
U.S. Food & Drug Administration. Real-Time Oncology Review Pilot Program. https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review-pilot-program. Updated October 7, 2020. Accessed March 5, 2021.
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 March 12, 2021.
American Cancer Society. What is Stomach Cancer? https://www.cancer.org/cancer/stomach-cancer/about/what-is-stomach-cancer.html. Updated January 22, 2021. Accessed March 5, 2021.
American Cancer Society. Key Statistics About Stomach Cancer. https://www.cancer.org/cancer/stomach-cancer/about/key-statistics.html. Updated January 22, 2021. Accessed March 5, 2021.
SEER. Cancer Stat Facts: Stomach Cancer. https://seer.cancer.gov/statfacts/html/stomach.html. Accessed March 5, 2021.
American Cancer Society. Stomach Cancer Survival Rates. https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/survival-rates.html. Updated January 22, 2021. Accessed March 5, 2021.
Bhurwal A, Brahmbatt B, Choudhry A, et al. Incidence of GE junction cancer continues to rise – analysis of SEER database. Gastrointestinal Endoscopy. 2019;89(6):AB362.https://doi.org/10.1016/j.gie.2019.03.522.
American Cancer Society. Key Statistics for Esophageal Cancer. https://www.cancer.org/cancer/esophagus-cancer/about/key-statistics.html. Updated January 12, 2021. Accessed March 5, 2021.
SEER. Cancer Stat Facts: Esophageal Cancer. https://seer.cancer.gov/statfacts/html/esoph.html. Accessed March 5, 2021.
American Cancer Society. Survival Rates for Esophageal Cancer. https://www.cancer.org/cancer/esophagus-cancer/detection-diagnosis-staging/survival-rates.html. Updated January 29, 2021. Accessed March 5, 2021.
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