US authorities have approved a “breakthrough” drug to treat advanced non-small cell lung cancer, signalling a paradigm shift in the way the deadliest of all cancers is treated.
In the largest study published to date using immunotherapy to treat lung cancer, the drug Keytruda (pembrolizumab) was tested on approximately 500 patients with non-small cell lung cancer.
Because so many of the patients in the study showed significant long-lasting responses, in October 2014 the US Food and Drug Administration (FDA) granted the drug “breakthrough therapy” status for use in lung cancer, allowing it to be fast-tracked for approval.
“The approval of this drug and a test to identify patients most likely to benefit has the potential to transform the way that lung cancer is treated,” said Dr. Edward Garon, the study’s principal investigator and a researcher at University of California, Los Angeles’ Jonsson Comprehensive Cancer Center.
“The quality and duration of disease response that was seen in the trial had previously been extremely rare in lung cancer. For people battling this deadly disease, this approach provides real hope of long-lasting responses while avoiding the toxicities of typical chemotherapy,” he said.
The response rate and duration of response for Keytruda were much greater than for drugs traditionally used to treat lung cancer. In the three-year clinical trial, the overall response rate (the percentage of people in whom tumours were substantially reduced in size) was 19 per cent. In people who responded to treatment, the average duration of response exceeded one year, a remarkable advance in this difficult disease.
Keytruda, a drug that has already been proven to extend the lives of people with advanced melanoma, is an antibody that targets the protein PD-1, which is expressed by immune cells. When it binds to another protein called PD-L1, PD-1 acts as an immune checkpoint, dampening the immune system’s T cells which otherwise could attack cancer cells, said Dr. Garon.
Some tumours are able to evade an immune response by expressing high levels of PD-L1. So by blocking the interaction between PD-1 and PD-L1, Keytruda in effect enables the patient’s immune system to attack the cancer.
Since PD-L1 binding to PD-1 prevents the T cells from attacking cancer cells, it was thought that higher levels of PD-L1 in tumours could correlate with favourable clinical outcomes with PD-1 inhibitor treatment.
Approximately a quarter of screened patients in the trial had PD-L1 expression in at least half of their tumour cells. Among these patients, the overall response rate was nearly 50 per cent.
The study was the first to validate that clinical outcomes with this class of drug were directly associated with the level of PD-L1 expression.
