Cancer Therapies

Pembroloizumab , a PDL-1 inhibitor, for advanced lung and head and neck cancers

Lung cancer is one of the leading causes of cancer-associated deaths worldwide. Standard treatment of advanced non-small cell lung cancer follows a regimen of platinum-based chemotherapy with or without maintenance therapy followed by a second line treatment with cytotoxic chemotherapeutic agents.

In cancers, programmed cell death 1 (PD-1) is present on the surface of T-cells which is involved in the body’s immune response to cancer. PD-1 can bind to one of its ligands, PD-L1 or PD-L2, and inhibit a cytotoxic T-cell response.

Pembrolizumab, a highly selective, humanized monoclonal IgG4 kappa isotype antibody against PD-1, blocks PD-1 association with its ligands so that the patient’s own immune cells are able to attack the cancer. This pathway was found to produce favorable responses in patients with advanced non-small cell lung cancer. Encouraging results in a clinical trial with pembrolizumab treatment were found in a special subgroup of patients with PD-L1 expression in their lung tumor or inflammatory cells. overall survival was prolonged; acceptable side-effects were noted. This landmark trial and the findings prompted the approval of pembrolizumab in patients with advanced non-small cell lung cancer among patients who test positive for this protein. Benefits have been observed among patients if at least one other chemotherapy has also been tried. This established the efficacy and safety of pembrolizumab in patients with advanced non-small cell lung cancer was recommended. Pembrolizumab is recommended to be given by intravenous injection of 2 mg/kg every 3 weeks. It is suggested that pembrolizumab should be used and then stopped at two years if a person’s disease has not worsened.

Another indication for the use of intravenous pembrolizumab at 200 mg every 3 weeks has been approved in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression during or after platinum-containing chemotherapy. Patients with recurrent or metastatic HNSCC have few treatment options, and new therapies are always being explored because of the associated high mortality rate. Although clinical trials are continuing to firmly establish pembrolizumab therapy, the USFDA granted accelerated approval based on initial findings of benefit in advanced head and neck cancer patients especially among those whose tumors were positive for human papilloma virus. In PD-L1 patients with advanced HNSCC, pembrolizumab demonstrated clinically meaningful anti-cancer activity. However, some immune-mediated adverse reactions have been noted that include pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis, and if severe and persistent, the drug should be withheld or discontinued and corticosteroids administered.

In conclusion, considering the significant mortality associated with both advanced non-small cell lung cancers as well as head and neck cancers, it is very encouraging to find immunotherapies such as pembrolizumab providing benefit in improved survival rates in these patients. However, researchers are pursuing to find more and more improved therapies for advanced cancers.