Oncology Overview: Taking a Closer Look at Nivolumab Immunotherapy

Nivolumab (Opdivo; Bristol Myers Squibb) is an immunotherapy that is FDA approved for 11 cancer indications,¹ with the most recent approval for use in combination with certain chemotherapy for the initial treatment of gastric cancer.² This latest action marks an important milestone as the first FDA-approved immunotherapy for first-line treatment of gastric cancer.²

Pharmacists can play an important role in managing patients receiving nivolumab therapy.

Indications

Nivolumab was approved April 16, 2021 and previously received priority review, and breakthrough therapy, and orphan drug designations for use in combination with fluoropyrimidine and platinum-containing chemotherapy for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.² Approval was based on the phase 3 CheckMate-649 trial (NCT02872116) that demonstrated nivolumab plus chemotherapy had superior overall survival compared with chemotherapy alone (P = 0.0002).³ Additionally, 55% of patients in the nivolumab plus chemotherapy group were alive at 1 year compared with 48% patients in the chemotherapy alone group.³

Additional cancers treated by nivolumab includes the following:¹

1. Melanoma
2. Non-Small Cell Lung Cancer (NSCLC)
3. Malignant Pleural Mesothelioma
4. Renal Cell Carcinoma (RCC)
5. Classical Hodgkin Lymphoma (cHL)
6. Squamous Cell Carcinoma of the Head and Neck (SCCHN)
7. Urothelial Carcinoma
8. Colorectal Cancer
9. Hepatocellular Carcinoma (HCC)
10. Esophageal Cancer

Mechanism of Action

Opdivo is a monoclonal antibody that works by binding to the PD-1 receptor and inhibits tumor growth by enhancing T-cell function.^1,2

Dosage and Administration

Nivolumab is administered by intravenous (IV) infusion over 30 minutes, and the dosage depends on the indication (see Table 1) and whether it is given as combination treatment or monotherapy.¹ Nivolumab can be administered in combination with ipilimumab (Yervoy; Bristol Myers Squibb), cabozantinib (Cabometyx; Exelixis), fluoropyrimidine and platinum-containing chemotherapy.¹ Nivolumab should be administered first followed by these therapies on the same day when being used as combination treatment: ipilimumab; platinum-doublet chemotherapy; ipilimumab and platinum-doublet chemotherapy (administer nivolumab, followed by ipilimumab, then platinum-doublet chemotherapy); and fluoropyrimidine and platinum-containing chemotherapy.

Warnings, Precautions, and Patient Counseling Points

Nivolumab can cause severe or life-threatening immune-mediated adverse reactions, so it is vital for pharmacists to monitor and educate patients about the possible signs and symptoms to watch for, and recommend seeking medical attention immediately if they experience them to determine whether therapy should be withheld or discontinued (see Table 2).1 It is important to especially monitor patients’ liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.1 Individuals who received allogeneic hematopoietic stem cell transplantation can experience severe or fatal complications if they underwent transplantation before or after nivolumab therapy, so it is critical to closely monitor patients.¹

Patients experiencing severe infusion-related reactions should have nivolumab withheld. Nivolumab should be permanently discontinued for life-threatening immune-mediated adverse reactions, recurrent severe immune-related reactions that require systemic treatment, or the inability to reduce the corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of starting steroid therapy. The infusion can be interrupted or the rate slowed in patients with mild or moderate infusion-related reactions.¹

Pregnancy and Lactation

Based on data from animal studies, nivolumab can cause fetal harm when administered to pregnant women. Women of child bearing potential should receive a pregnancy test before starting nivolumab treatment. Patients should be counseled to use an effective birth control during treatment and for at least 5 months after the last dose of Opdivo. It is unknown whether nivolumab passes into the breast milk so patients should be advised to avoid breastfeeding during treatment and for 5 months after the last dose.¹

REFERENCES

1. Opdivo. Prescribing information. Bristol Myers Squibb; 2021. Accessed July 10, 2021.https://packageinserts.bms.com/pi/pi_opdivo.pdf
2. FDA approves first immunotherapy for initial treatment of gastric cancer [News release].FDA. April 16, 2021. Accessed July 10, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-first-immunotherapy-initial-treatment-gastric-cancer.
3. 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, regardless of PD-L1 expression status [News release]. April 16, 2021, Bristol Myers Squibb. Accessed July 10, 2021.https://news.bms.com/news/corporate-financial/2021/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/default.aspx.