October has been a big month for lung cancer patients, and for checkpoint inhibitor immunotherapies. On October 9, the FDA approved the anti-PD-1 pembrolizumab for first-line treatment of advanced lung cancer, and now, 8 days later they approved yet another checkpoint drug―the anti-PD-L1 atezolizumab―for lung cancer patients.
This approval was granted after the phase III OAK clinical trial showed that atezolizumab, which is manufactured by Genentech and marketed under the name TECENTRIQ®, helped patients live longer than those treated with docetaxel chemotherapy. Like the pembrolizumab trial, this atezolizumab trial also used PD-L1 expression to select non-small cell lung cancer (NSCLC) patients for this PD-1 pathway blockade therapy. This reflects the recent push towards smarter therapeutic approaches: rather than doctors blindly treating all patients the same, they’re using biomarkers to predict which patients are the most likely to benefit from treatments, which allows them to choose patients wisely and improve the chances of success.
Two anti-PD-1 checkpoint immunotherapies, Merck’s pembrolizumab and Bristol-Myers Squibb’s nivolumab, have already been approved for lung cancer, but this is the first drug to target the PD-L1 ligand instead of the PD-1 receptor. While they are all antibodies with the same goal―to block PD-1 pathway signaling―they have important differences.
In fact, Rony Dahan, Ph.D., a CRI-funded postdoctoral fellow at The Rockefeller University, published work showing that the “back ends” of these molecules (the side that doesn’t bind PD-1 or PD-L1) actually have opposite functions. With the PD-1 drugs like pembrolizumab, activating these back ends makes the drugs less effective. On the other hand, with anti-PD-L1 drugs like atezolizumab, activating these back ends actually makes them work better. This science is still very new, so more work needs to be done to figure out how to use this information to help patient in the clinic.
Furthermore, unlike the pembrolizumab approval, atezolizumab unfortunately won’t be available for lung cancer patients as a first option just yet. Right now, it’s only available for advanced lung cancer patients who have failed other treatments, such as platinum-based chemotherapy and drugs designed to target specific mutations. On the bright side, Genentech is currently testing atezolizumab, which is already approved for bladder cancer, in 8 clinical trials and has more planned, so hopefully its benefits will soon be extended to more patients.