Sarah Goldberg, MD, MPH
Though the immunotherapy agents nivolumab (Opdivo) and pembrolizumab (Keytruda) have gained traction in the treatment paradigm of non–small cell lung cancer (NSCLC) and are also preferred as a second-line treatment of choice, several questions still remain—including the efficacy of PD-L1 as a biomarker, explains Sarah Goldberg, MD, MPH.
In October 2015, pembrolizumab was granted an accelerated approval by the FDA as a treatment for patients with pretreated advanced NSCLC across all histologies whose tumors express PD-L1. The agent was approved along with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, and is indicated for patients who progressed on or after platinum-containing chemotherapy or EGFR
- or ALK
-targeted agents in patients harboring those mutations.
Most recently, the FDA accepted a supplemental new drug application for pembrolizumab as a treatment for patients with advanced NSCLC with PD-L1 expression on >1% of tumor cells.
Also in October 2015, the FDA expanded the approval of nivolumab (Opdivo) to include patients with nonsquamous NSCLC who progress on or following platinum-based chemotherapy, or EGFR
- or ALK
-targeted agents in patients who have those mutations.
In an interview with OncLive
at the 3rd Annual
Miami Lung Cancer Conference®, Goldberg
, an assistant professor of Medicine and Medical Oncology at Yale Cancer Center, discusses the efficacy of immunotherapies, PD-L1 as a biomarker, and how these therapies will continue to alter the treatment of patients with NSCLC.
OncLive: How could the role of PD-L1 continue to evolve as a biomarker?
: That's one of the biggest questions that we have in the research world and in standard practice now that these drugs are available. PD-L1 is a test you can do for your patients in the clinic, but the question is, "Should you, and what does it mean when you get a positive or negative result?"
Patients who have PD-L1 expression in their tumor, it seems as though they have a better chance of responding to any of the agents that have been being tested—nivolumab, pembrolizumab, atezolizumab—they all seem to have more of a benefit when a tumor has PD-L1 expression.
The complicating factor is patients who do not have PD-L1 expression in their tumor also show benefit from these drugs. It is a lower benefit, but there still can be benefit. Then the question is, "Why should you test if there's still benefit in the negative patients?" It's a complicated answer. For some patients you don't need to test, I would say, because if you were going to use that drug anyway regardless of the results, then why would you need to know the answer? That's specifically true for nivolumab, regardless of PD-L1 status. Therefore, you don't need to test.
For pembrolizumab, the trials were done in patients who were PD-L1–positive. That's where the benefit was seen, and so that's why that drug is only approved in patients who are PD-L1–positive. To go with that drug, you should undergo the testing. I think there is still some benefit in patients who are PD-L1–negative, so whether or not you need to test is complicated. Overall, I don't tend to test because I feel like if you're going to use the drug anyway; therefore, I wouldn't need to know the results.
It might change when we start to use the drug in the first-line setting, when you really want to know whether or not a patient is positive or negative, because you want to see that higher chance of benefit when you want to use that option, specifically a platinum-based doublet. When you have that as an option then you want to have a higher degree of confidence that you're going to get a response with that immune therapy. The drugs are only approved in the second-line setting, so for that setting I tend not to test and treat anyway.
Is there a favoring of nivolumab over pembrolizumab since pembrolizumab requires testing?
That's being seen in a lot of different practices. One of the other differences between the two drugs when they were approved is how often they are given. Nivolumab is administered every 2 weeks and pembrolizumab is given every 3 weeks, so if that's a consideration, then that might be a reason to test. Even if it is negative, I would still consider giving it in a lot of situations. I think oncologists need to think about testing, what it will mean for their results, and how it'll change their practice.