Despite the definitive and durable efficacy of PD-1/PD-L1 inhibitors and their low adverse effects, such good results are not achieved in all patients. In unscreened populations, PD-1/PD-L1 inhibitors alone are only 20% effective on average, with a median time to onset of action of 12 to 16 weeks[. Therefore, failure to screen is likely to delay patient treatment.
How to screen for people who may benefit from PD-1/PD-L1 inhibitor therapy is a major clinical challenge. Among the metrics that have been found to provide help in predicting efficacy in studies are PD-L1, TMB (tumor mutational load), and MSI (microsatellite instability)/dMMR (defective mismatch gene repair), as detailed in “Which metrics predict efficacy of PD-1/PD-L1? What is the accuracy? for answers to the Q&A.
Related reading:
In addition to the three markers mentioned above, there are many other markers under investigation, such as tumor-infiltrating lymphocytes, neoantigen levels, immune-related signature expression profile tags, and so on. However, they are not yet able to fully interpret and predict the efficacy of immunotherapy. Because of the complexity of the tumor microenvironment, scientists still have a long way to go to accurately predict the efficacy of PD-1/PD-L1 inhibitors.
Co-reviewed by Dr. Zhen Wang, Deputy Chief Physician, Guangdong Provincial People’s Hospital Guangdong Lung Cancer Institute Xiaoxiao Peng