The following article, written by Adam Peele, PharmD, MHA, BCPS, BCOP, Director of Pharmacy Operations at Oncology Analytics, is the second of a four-part series on key trends and findings from the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, held May 29-31, 2020.
Lung cancer is the leading cause of cancer-related death in the United States. Less than 20% of all patients diagnosed with lung cancer are alive for more than five years after their initial diagnosis. Almost 90% of lung cancer is caused by cigarette smoking.
Lung cancer is divided into two types: non-small cell lung cancer and small cell lung cancer. Small cell lung cancer is a more aggressive form, but non-small cell lung cancer is the more common type, accounting for approximately 80% of all cases. More than half of patients with non-small cell lung cancer present with stage IV disease. Stage IV disease, also referred to as metastatic cancer, occurs when cancer has spread from the lung to other areas of the body such as the bones, liver, and brain.
New York Yankees great Joe DiMaggio had surgery to remove a cancerous tumor from his lung. CNN host Larry King had part of his lung removed due to a stage 1 lung cancer. Walt Disney, a lifelong smoker, died of lung cancer ten days after his 65th birthday. Disney’s daughter was active in efforts to curb youth access to tobacco in efforts to help limit smoking at an early age.
As the medical community’s understanding of cancer continues to progress, new treatment options are coming to market quickly. One area that has generated a lot of momentum involves checkpoint proteins within the immune system. When an interaction between checkpoint proteins, such as programmed death-ligand 1 (PD-L1) on non-host cells (like foreign bacteria) and programmed cell death protein 1 receptors (PD-1) on T-cells, the immune response to the invader is suppressed. A second protein, known as cytotoxic T-lymphocyte associated protein 4 (CTLA-4), is similar to the brake system on a vehicle. When active, CTLA-4 also helps to downregulate immune responses and put the “brakes” on the immune response.
The immune system also recognizes cancer as a foreign entity and begins to mount a response. Recent research has shown that certain cancers express PD-L1, which enables cancer to “hijack” the immune system and evade destruction. Checkpoint inhibitors such as nivolumab interfere with PD-L1 to PD-1 binding and prevent the disease from suppressing the immune system. Ipilimumab, a CTLA-4 antagonist, blocks the actions of CTLA-4, which increases the immune response against the tumor.
At ASCO 2020, results of a clinical trial called CheckMate 9LA were reported. CheckMate 9LA was an open-label, phase 3 study that enrolled patients with stage IV or recurrent non-small cell lung cancer without EGFR or ALK mutations and no previous systemic treatment. Patients were randomized to nivolumab 360 mg every three weeks, ipilimumab 1 mg/kg every six weeks, and two cycles of platinum-containing chemotherapy or chemotherapy every three weeks for four cycles with an option to continue maintenance therapy in patients with appropriate histology. The trial continued until progressive disease, unacceptable toxicity, or two years of maintenance immunotherapy was completed. The addition of nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy led to a 31% reduced risk of death versus chemotherapy alone. The overall survival benefit was seen across all histologies of non-small cell lung cancer and was observed regardless of PD-L1 expression.
Given these results, Food and Drug Administration approval was awarded to the regimen (nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy) for previously untreated patients with non-small cell lung cancer. CheckMate 9LA further proves that the immune system can be effectively harnessed in the fight against cancer.