Pembrolizumab & Nivolumab
In September 2014 the US Food and Drug Administration approved Merck's drug pembrolizumab (Keytruda)
a PD1 inhibitor, for the treatment of patients with advanced melanoma failing treatment with a drug called
ipilumimab (Yervoy).
Nivolumab (Opidvo), a PD-L1 inhibitor, from Bristol-Myers Squibb and Ono Pharmaceutical, was approved
for the treatment of advanced melanoma in Japan in August 2014.
Pembrolizumab and Nivolumab are not currently registered in New Zealand.
How They Work
The goal of immune-oncology therapy is to use the body’s own immune system to find and kill cancer cells.
Our immune system is designed to continuously recognize and eliminate unwanted antigens
(bacteria/viruses/cancer cells) to help prevent infection and disease. When an antigen is detected by the
body’s immune system, it triggers the production and release of defence mechanisms such as T-Cells or killer
cells that search out and help destroy these unwanted invaders. Studies have suggested that this same
process eliminates the vast majority of cancer cells before they can establish themselves and form a tumour.
However, some cancer cells have developed the ability to evade detection from our immune system; this
allows them to grow until such time they are big enough to be detected as a cancer. One method of evasion
is the ability of certain cancer cells to produce a protein called PD1 (also known as Programmed Cell Death
protein 1).
PD1 is like an ‘off switch’ for your defence systems T-cells. It is used routinely by our immune system to tell
the T-Cells that their job is done and the antigen (virus/bacteria/cancer cell) has been eliminated or is under
control. The release of PD1 tells the T-cells to stop what they doing and become dormant. This is an
important step in our immune pathway to stop T-cells becoming out of control and attack normal healthy
tissue.
Cancer cells that express PD1 have developed the ability to switch off T-Cells before they can destroy them,
and by doing so, it allows the cancer cell to carry on and replicate undetected and eventually grow to form a
cancerous tumour.
PD1/PD-L1 Inhibitors
PD1/PDL1 inhibitors are a new developing therapy area that helps block the cancer cell from switching off
the activity of the T-Cell through the PD1 mechanism. In doing so this prevents the cancer cells from evading
detection and allows immune system including T-Cells to destroy them.
Clinical Studies
Recent clinical studies have shown that PD-1/PD-L1 inhibitors are effective across several cancer types,
including melanoma; lung, bladder, kidney, stomach cancers; and Hodgkin lymphoma. These cancers are
being targeted with PD-1/PD-L1 inhibitors used either alone or in combination with other targeted or nontargeted therapies limiting tumour growth and promoting tumour shrinkage.
The clinical studies undertaken so far have shown that PD-1 and PD-L1 inhibitors have an acceptable safety
profile and have in some patients resulted in durable responses even after stopping treatment.
(This information was supplied by MSD NZ)