Kartik Konduri, MD
Single-agent and combination immunotherapy continue to show positive results in patients with non–small cell lung cancer (NSCLC), especially those who have biomarker-driven disease.
In an interview during the meeting, he shared insight on these molecular developments, recently presented or discussed clinical trials, and steps the field needs to take to continue moving in a biomarker-driven paradigm of NSCLC treatment.
OncLive: What is important to note in how the field is changing regarding biomarkers?
: The lung cancer landscape is changing and, as we go about on a day-to-day basis, we are finding new discoveries about how patients are potentially noted to have markers that can be utilized for treatment. Some of them can be molecular markers, where you are utilizing targeted therapies, and there are circumstances where secondary mutations of resistance mutations occur. Resistances can occur in the form of escape mechanisms or amplifications of the target, and new drugs have come out, which potentially can be evaluated for treatment.
We know that it is not a perfect biomarker, however, and we are in search of more. TMB and other evaluations, including T-effector gene signatures, are being looked at as possible biomarkers for the future.
Can you expand on these clinical trials?
Multiple clinical trials are looking at immunotherapy biomarkers, and TMB has come to the forefront. Various trials have suggestive benefit—from evaluation in the CheckMate-026 trial, there was a TMB benefit in outcomes of PFS. There were also trials looking at small cell lung cancer, for example, such as in the CheckMate-032 trial. This was a small trial, but it did show benefit for high TMB having good response rates for patients with ipilimumab in combination with nivolumab or nivolumab on its own.
A recent trial that has been spoken about without actual data being presented is CheckMate-227, which is a combination of immunotherapy agents that have been shown to improve PFS for a specific subset of patients who are known to have high TMB. Then, there are trials that have looked at T-effector gene signatures, particularly the IMpower150 study, which has shown improvements in PFS.
Of these trials, which would you consider to be the most practice changing?
The trial that has changed practice over the last few years was the KEYNOTE-024 trial. It allowed for high PD-L1 expression to suggest a subset of patients who will have a good benefit in terms of PFS and overall survival in lung cancer.
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