Immune Checkpoint Inhibitors in Oncology: Nivolumab (Opdivo)

Tumour cells harness multiple resistance mechanisms to evade the host-tumour immune system. Notably, the programmed death 1 (PD1) receptor and its ligands, PD-L1 and PD-L2, play critical roles in T-cell suppression and exhaustion. Overexpression of PD-L1 and PD1 on tumour cells and tumour-infiltrating lymphocytes, respectively, is associated with poor disease outcomes in terms of progression-free survival (PFS) and overall survival (OS) in some human cancers. In this article, we will dive into the profile of Nivolumab

Nivolumab’s Drug Profile, Indications and Key Trials

Nivolumab (Opdivo) is a human immunoglobulin monoclonal antibody designed to address tumour PD1 exploitation by binding to the PD1 receptor, thereby inhibiting its interaction with PD-L1 and PD-L2. The immune checkpoint inhibitor restores the PD1 pathway-mediated inhibition of the immune response and reduces the immunosuppressive microenvironment of the tumour. The drug has been extensively investigated in multiple clinical settings, proving efficacious in the treatment of non-small cell lung carcinoma (NSCLC), melanoma, renal cell carcinoma (RCC) and other cancers. In Singapore, nivolumab is approved for use in over 9 cancers. A summary of its labelled indications and key trials are described in Table 1.

Within the same drug class, Singapore’s Health Sciences Authority (HSA) has also approved the use of pembrolizumab (Keytruda) for indications that partially overlap. Notably, the PD1 inhibitors have NOT been evaluated head-to-head in a controlled trial setting. In practice, the choice of either agent often weighs on patient and clinician preference. To date, molecular, preclinical, and early clinical data on nivolumab and pembrolizumab support the conclusions that both drugs may well be interchangeable. In the setting of recurrent or advanced NSCLC, a real-world evidence study by Cui et al. 2020, observed similar survival benefits between agents.

Safety profile

From a safety perspective, nivolumab treatment is generally well tolerated. The most common adverse events (AEs) reported include fatigue, decreased appetite, diarrhoea, nausea, cough, dyspnoea, constipation, vomiting, rash, pyrexia, and headache. Immune-related AEs (irAEs) are of special interest due to the drug’s mechanistic upregulation of immune cells. A meta-analysis by A Almutairi et al. determined that the most frequent potential irAEs among nivolumab users were maculopapular rash, erythema, hepatitis, and infusion-related reactions. In addition, combination therapies were found to elevate the incidence of potential irAEs. Notwithstanding, irAEs have proven generally manageable or reversible, with the support of clinical guidelines. 

Table 1: Indications and Key Trials