Clinical Decisions in Non-Driver NSCLC - Episode 4
Benjamin P. Levy, MD:We now have 3 drug approvals for second-line nonsmall cell lung cancer, with immunotherapy. We’ve got single-agent pembrolizumab, single-agent nivolumab, and single-agent atezolizumab, all showing superior outcomes when compared with docetaxel. Pembrolizumab and nivolumab are PD-1 drugs. Atezolizumab is a PD-L1 drug. If you look at cross-trial comparisons between KEYNOTE-010, CheckMate-017 and CheckMate-057, and the OAK trial, these drugs elicit similar response rates and similar outcomes overall. So, it’s hard for me to really state that one of these drugs is better than the other. Numerically, the longest overall survival we’ve had from an immunotherapy has been from the OAK trial, and that was 13.2 months, which exceeds the survival we saw with pembrolizumab and nivolumab in the KEYNOTE and CheckMate trials, respectively.
That said, I think it’s really dealer’s choice and what you feel familiar with. Nivolumab has now moved to be an every-4-week regimen. Pembrolizumab and atezolizumab as second-line drugs are every 3 weeks. It’s just what you’re comfortable with. There’s some biological rationale why atezolizumab, a PD-L1 drug, may have less toxicity. But I can tell you, in my experience, the toxicities between these 3 agents are fairly similar.
Assessing a response in a patient with immunotherapy can be a challenge. There have been other immune-related response criteria that have been looked at as well. It’s sometimes difficult because these drugs are not cytotoxic and they’re not going to elicit responses similar to what we see in something like chemotherapy and antiangiogenic strategies. There is pseudoprogression that we need to factor in here with these drugs. The rate of pseudoprogression is low, and there are hyper-progressers, toopeople who receive these drugs who progress quite rapidly. But I think we need to be mindful that there may be changes within the tumor, elicited by these drugs, that don’t necessarily mean the patient is progressing. It may have to do with the fact that there’s more T-cell trafficking in an inflamed tumor that may show something on a scan that looks bigger. But nevertheless, the patient is deriving a benefit. I think we need to be very diligent when we’re looking at the responses. I still image patients every 4 to 6 treatments, or every 3 months, on these drugs. But I’m very careful when I look at the images when making a decision to move forward.
Transcript edited for clarity.