Initial US Approval:
2014
Key Clinical Studies:
CHECKMATE-8HW (NCT04008030)
Drug Class/Description:
Programmed death receptor-1 (PD-1)-blocking antibody in combination with a monoclonal antibody against CTL antigen 4 (CTLA-4)
Indications and Usage:
Melanoma
- Adult and pediatric (12 years and older) patients with unresectable or metastatic melanoma, as a single agent or in combination with ipilimumab.
- For the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.
Non-Small Cell Lung Cancer (NSCLC)
- Adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer in the neoadjuvant setting, in combination with platinum-doublet chemotherapy.
- Adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer and no known EGFR mutations or ALK rearrangements, for neoadjuvant treatment, in combination with platinum-doublet chemotherapy, followed by singleagent OPDIVO as adjuvant treatment after surgery.
- Adult patients with metastatic non-small cell lung cancer expressing PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with ipilimumab.
- Adult patients with metastatic or recurrent non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations as first-line treatment, in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy.
- Adult patients with metastatic non-small cell lung cancer and progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
Malignant Pleural Mesothelioma
- Adult patients with unresectable malignant pleural mesothelioma, as first-line treatment in combination with ipilimumab.
Renal Cell Carcinoma (RCC)
- Adult patients with intermediate or poor risk advanced renal cell carcinoma, as a first-line treatment in combination with ipilimumab.
- Adult patients with advanced renal cell carcinoma, as a first-line treatment in combination with cabozantinib.
- Adult patients with advanced renal cell carcinoma who have received prior antiangiogenic therapy.
Classical Hodgkin Lymphoma (cHL)
- Adult patients with classical Hodgkin lymphoma that has relapsed or progressed after a:
- autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, or
- 3 or more lines of systemic therapy that includes autologous HSCT.
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
- Adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy.
Urothelial Carcinoma
- Adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.
- Adult patients with unresectable or metastatic urothelial carcinoma, as first-line treatment in combination with cisplatin and gemcitabine.
- Adult patients with locally advanced or metastatic urothelial carcinoma who:
- have disease progression during or following platinum-containing chemotherapy.
- have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Colorectal Cancer
- Adult and pediatric (12 years and older) patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) in combination with ipilimumab.
- Adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
Hepatocellular Carcinoma (HCC)
- In combination with ipilimumab in adult patients with unresectable or metastatic HCC who have been previously treated with sorafenib.
Esophageal Cancer
- Adult patients with completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease, who have received neoadjuvant chemoradiotherapy (CRT).
- Adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma as first-line treatment in combination with fluoropyrimidine- and platinum-containing chemotherapy.
- Adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma as first-line treatment in combination with ipilimumab.
- Adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.
Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma
- Adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma in combination with fluoropyrimidine- and platinum-containing chemotherapy.a
aThis indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Dosage and Administration:
- Administer by intravenous infusion after dilution based upon recommended infusion rate for each indication.
- Unresectable or metastatic melanoma
- Adult and pediatric patients weighing 40 kg or greater: 240 mg every 2 weeks or 480 mg every 4 weeks.
- Pediatric patients weighing less than 40 kg: 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks.
- Adult and pediatric patients weighing 40 kg or greater: 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks.
- Pediatric patients weighing less than 40 kg: 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks for 4 doses, then 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks.
- Adjuvant treatment of melanoma
- Adult and pediatric patients weighing 40 kg or greater: 240 mg every 2 weeks or 480 mg every 4 weeks.
- Pediatric patients weighing less than 40 kg: 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks.
- Neoadjuvant treatment of resectable (tumors ≥4 cm or node positive) non-small cell lung cancer
- 360 mg with platinum-doublet chemotherapy on the same day every 3 weeks for 3 cycles.
- Neoadjuvant and adjuvant treatment of resectable non-small cell lung cancer
- 360 mg with platinum-doublet chemotherapy on the same day every 3 weeks for up to 4 cycles, then continued as single-agent OPDIVO (nivolumab) 480 mg every 4 weeks after surgery for up to 13 cycles (~1 year).
- Metastatic non-small cell lung cancer
- 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks.
- 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks and 2 cycles of platinum-doublet chemotherapy.
- 240 mg every 2 weeks or 480 mg every 4 weeks.
- Malignant pleural mesothelioma
- 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks.
- Advanced renal cell carcinoma
- 3 mg/kg followed by ipilimumab 1 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks.
- 240 mg every 2 weeks or 480 mg every 4 weeks administered in combination with cabozantinib 40 mg once daily without food.
- 240 mg every 2 weeks or 480 mg every 4 weeks.
- Classical Hodgkin lymphoma
- 240 mg every 2 weeks or 480 mg every 4 weeks.
- Recurrent or metastatic squamous cell carcinoma of the head and neck
- 240 mg every 2 weeks or 480 mg every 4 weeks.
- Adjuvant treatment of urothelial carcinoma
- 240 mg every 2 weeks or 480 mg every 4 weeks.
- First-line unresectable or metastatic urothelial carcinoma
- 360 mg every 3 weeks with cisplatin and gemcitabine on the same day for up to 6 cycles, then 240 mg every 2 weeks or 480 mg every 4 weeks.
- Previously treated locally advanced or metastatic urothelial carcinoma
- 240 mg every 2 weeks or 480 mg every 4 weeks.
- Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer
- Adult and pediatric patients weighing 40 kg or greater: 240 mg followed by ipilimumab 1 mg/kg on the same day every 3 weeks for a maximum of 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks.
- Pediatric patients weighing less than 40 kg: 3 mg/kg followed by ipilimumab 1 mg/kg on the same day every 3 weeks for a maximum of 4 doses, then 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks.
- Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following prior treatment for metastatic disease.
- Adult and pediatric patients weighing 40 kg or greater: 240 mg every 2 weeks or 480 mg every 4 weeks.
- Pediatric patients weighing less than 40 kg: 3 mg/kg every 2 weeks.
- Hepatocellular carcinoma
- 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks.
- Adjuvant treatment of resected esophageal or gastroesophageal cancer
- 240 mg every 2 weeks or 480 mg every 4 weeks for total treatment duration of 1 year.
- Esophageal squamous cell carcinoma
- 240 mg every 2 weeks or 480 mg every 4 weeks in combination with chemotherapy regimen of fluoropyrimidine- and platinum-containing chemotherapy.
- 3 mg/kg every 2 weeks or 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks.
- 240 mg every 2 weeks or 480 mg every 4 weeks.
- Gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma (GC, GEJC, or EAC)
- 360 mg every 3 weeks with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks.
- 240 mg every 2 weeks with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks.
- See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions.
Dosage Forms and Strengths:
- Injection: 40 mg/4 mL (10 mg/mL), 100 mg/10 mL (10 mg/mL), 120 mg/12 mL (10 mg/mL), and 240 mg/24 mL (10 mg/mL) solution in a single-dose vial.
Contraindications:
None.
Warnings and Precautions:
- Immune-Mediated Adverse Reactions:
- Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis and hepatotoxicity, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, and immune-mediated nephritis and renal dysfunction.
- Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.
- Withhold or permanently discontinue based on severity and type of reaction.
- Infusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue OPDIVO (nivolumab) based on severity of reaction.
- Complications of allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody.
- Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception.
- 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.
Adverse Reactions:
Most common adverse reactions (incidence ≥20%) in patients were:
- As a single agent: fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia, headache, abdominal pain, vomiting, and urinary tract infection.
- In combination with ipilimumab: fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, constipation, decreased weight, and dizziness.
- In combination with platinum-doublet chemotherapy: nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy.
- In combination with ipilimumab and platinum-doublet chemotherapy: fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus.
- In combination with cabozantinib: diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia syndrome, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.
- In combination with fluoropyrimidine- and platinum-containing chemotherapy: nausea, peripheral neuropathy, decreased appetite, fatigue, constipation, stomatitis, diarrhea, vomiting, abdominal pain, and musculoskeletal pain.
Use in Specific Populations:
- Lactation: Advise not to breastfeed.
Adapted From:
https://packageinserts.bms.com/pi/pi_opdivo.pdf
Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.
