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In patients with advanced ESCC previously treated with fluoropyrimidine- and platinum-based chemotherapy
OPDIVO® DEMONSTRATED
SUPERIOR OVERALL SURVIVAL
VS DOCETAXEL OR PACLITAXEL1
ESCC=esophageal squamous cell carcinoma.
The median OS was 10.9 months (95% CI: 9.2-13.3) for OPDIVO compared to 8.4 months (95% CI: 7.2-9.9) for docetaxel or paclitaxel (HR=0.77 [95% CI: 0.62-0.96]; P=0.0189).
Please see additional data below.
INDICATION
OPDIVO is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.
SELECT IMPORTANT SAFETY INFORMATION
Summary of Warnings and Precautions
OPDIVO is associated with the following Warnings and Precautions including immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion-related reactions; 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 additional Important Safety Information for OPDIVO below, and US Full Prescribing Information for OPDIVO.
Minimum follow-up (time from the date of randomization of last patient to data cutoff) was 17.6 months2
ORR was 19.3% (n=33/171) with OPDIVO (95% CI: 13.7–26.0) and 21.5% (n=34/158) for the docetaxel or paclitaxel group (95% CI: 15.4–28.8); P=0.6323 (not significant)1†
CR was 0.6% (n=1) with OPDIVO and 1.3% (n=2) for the docetaxel or paclitaxel group
PR was 18.7% (n=32) with OPDIVO and 20.3% (n=32) for the docetaxel or paclitaxel group
Median PFS was 1.7 months for OPDIVO (95% CI: 1.5–2.7) and 3.4 months for the docetaxel or paclitaxel group (95% CI: 3.0–4.2) with an HR of 1.1 (95% CI: 0.9–1.3)1‡
PFS was not tested for statistical significance due to pre-specified hierarchical testing strategy1
Serious Adverse Reactions
In Attraction-3, serious adverse reactions occurred in 38% of patients receiving OPDIVO (n=209). Serious adverse reactions reported in ≥2% of patients who received OPDIVO were pneumonia, esophageal fistula, interstitial lung disease and pyrexia. The following fatal adverse reactions occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).
Please see additional Important Safety Information below.
OPDIVO: the only I-O therapy approved in this patient population, regardless of tumor PD-L1 expression level1,2
OS benefit was observed regardless of PD-L1 status based on a pre-specified exploratory analysis1
In patients with PD-L1 ≥1%: mOS was 10.9 months with OPDIVO (n=101) vs 8.1 months with chemotherapy group (n=102) (HR=0.69; 95% CI: 0.51–0.94)1,2
In patients with PD-L1 <1%: mOS was 10.9 months with OPDIVO (n=109) vs 9.3 months with chemotherapy group (n=107) (HR=0.84; 95% CI: 0.62–1.14)1,2
Based on Response Evaluable Set (RES) analysis, n=171 in OPDIVO group and n=158 in investigator's choice group. P=0.6323, not significant.1
Based on ITT analysis.1
Common Adverse Reactions
In Attraction-3, the most common adverse reactions occurring in ≥20% of OPDIVO-treated patients (n=209) were rash (22%) and decreased appetite (21%).
Please see additional Important Safety Information below.
Attraction-3 trial design1,2: Attraction-3 was a multicenter, randomized (1:1), active-controlled, open-label trial in 419 patients with unresectable advanced, recurrent or metastatic ESCC who were refractory or intolerant to at least one fluoropyrimidine- and platinum-based regimen. The trial included patients regardless of PD-L1 status. The trial excluded patients who were refractory or intolerant to taxane therapy, had brain metastases that were symptomatic or required treatment, had autoimmune disease, used systemic corticosteroids or immunosuppressants, or had apparent tumor invasion of organs adjacent to the esophageal tumor or had stents in the esophagus or respiratory tract. Patients were stratified by region, number of organs with metastases, and PD-L1 status. Patients received OPDIVO 240 mg by IV infusion over 30 minutes every 2 weeks (n=210) or investigator’s choice of taxane chemotherapy of either docetaxel (n=65) 75 mg/m2 IV every 3 weeks, or paclitaxel (n=144) 100 mg/m2 IV once a week for 6 weeks followed by 1 week off. Patients were treated until disease progression, assessed by the investigator per RECIST v1.1, or unacceptable toxicity. The tumor assessments were conducted every 6 weeks for 1 year, and every 12 weeks thereafter. The major efficacy outcome measure was OS. Additional efficacy outcome measures were ORR and PFS as assessed by the investigator using RECIST v1.1 and DOR.
Recommended dosage: The recommended dosage of OPDIVO in the treatment of advanced ESCC is 240 mg every 2 weeks or 480 mg every 4 weeks as a 30-minute IV infusion, until disease progression or unacceptable toxicity.1
CI=confidence interval; CR=complete response; DOR=duration of response; HR=hazard ratio; I-O=immuno-oncology; ITT=intent to treat; IV=intravenous; mo=month; mOS=median OS; no=number; ORR=overall response rate; OS=overall survival; PD-L1=programmed death ligand 1; PFS=progression-free survival; PR=partial response; RECIST=Response Evaluation Criteria In Solid Tumors.
IMPORTANT SAFETY INFORMATION
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients.
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients.
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. Addition of an alternative immunosuppressive agent to the corticosteroid therapy, or replacement of the corticosteroid therapy, should be considered in corticosteroid-refractory immune-mediated colitis if other causes are excluded.
Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients.
Immune-Mediated Endocrinopathies
OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.
In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients.
Immune-Mediated Nephritis and Renal Dysfunction
OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients.
Immune-Mediated Skin Adverse Reactions
OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients.
Immune-Mediated Encephalitis
OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids.
Other Immune-Mediated Adverse Reactions
Based on the severity of the adverse reaction, permanently discontinue or withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO monotherapy, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1.0% of patients receiving OPDIVO: myocarditis, rhabdomyolysis, myositis, uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), motor dysfunction, vasculitis, aplastic anemia, pericarditis, and myasthenic syndrome.
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 and may require treatment with systemic steroids to reduce the risk of permanent vision loss.
Infusion-Related Reactions
OPDIVO can cause severe infusion-related reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion-related reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. 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.
Embryo-Fetal Toxicity
Based on mechanism of action, 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 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
It is not known whether OPDIVO is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from OPDIVO, advise women not to breastfeed during treatment and for at least 5 months after the last dose.
Serious Adverse Reactions
In Attraction-3, serious adverse reactions occurred in 38% of patients receiving OPDIVO (n=209). Serious adverse reactions reported in ≥2% of patients who received OPDIVO were pneumonia, esophageal fistula, interstitial lung disease and pyrexia. The following fatal adverse reactions occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).
Common Adverse Reactions
In Attraction-3, the most common adverse reactions occurring in ≥20% of OPDIVO-treated patients (n=209) were rash (22%) and decreased appetite (21%).
OPDIVO (10 mg/mL) is an injection for intravenous (IV) use.
Please see US Full Prescribing Information for OPDIVO.
For additional information, call 1-​85​5-OPD​IV​O-​1 (1-​85​5-​67​3-​48​61). Responses provided between 8:​00 A​M and 8​:0​0 PM ET, Mon​day–Fri​day.
For Live Support and Assistance
8​ A​M – 8​ P​M E​T
Mo​n​day – Fri​day
1-85​5-OP​DIVO-1
Sincerely,
Your OPDIVO Team
References:
1. OPDIVO [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2020.
2. Kato K, Cho BC, Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20:1506-1517.
3. Kato K, Cho BC, Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20:1506-1517 [protocol].
Bristol Myers Squibb is committed to transparency. For information on the list price of OPDIVO as well as information regarding average out-of-pocket costs and assistance programs, please visit our pricing information page.
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1506US2001622-01-01  07/20

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