Discussing Biomarkers and Best Options in NSCLC

Hossein Borghaei, MS, DO, is the chief of Thoracic Medical Oncology, professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, and the Gloria and Edmund M. Dunn Chair in Thoracic malignancies, provides an overview on his presentation given at the 18th Annual New York Lung Cancers Symposium®.

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0:10 | The management of metastatic non–small cell lung cancer relies on obtaining several biomarkers to direct treatment for patients appropriate treatment. Some of these are genomic alterations that are obtained either through DNA or RNA sequencing. The other biomarker that we look at is called PD-L1. In patients or tumors that basically have no PD-L1 expression or do not have a molecular alteration, the question was, what is the most appropriate treatment? Again, the context is that if you have a targetable lesion, targeted therapies can be affected. If there's any PD-L1 expression, that can get treatment but without PD-L1 expression. We've been relying on a combination of chemotherapy and immunotherapy for the most part, based on several randomized phase 3 published results suggesting that a checkpoint inhibitor combined with chemotherapy can be quite effective in the management of patients with this tumor profile.

1:10 | We also have data from several studies suggesting that a combination of immunotherapy without chemotherapy can be effective. CheckMate-227 [NCT02477826] included patients with PD-L1 negative tumors, although they were not part of the primary analysis group, statistically, it is hard to justify the treatment because again, we're not part of the statistical analysis group. In the POSEIDON study [NCT03164616] in combination of chemotherapy with tremelimumab [Imjudo] and durvalumab [Imfinzi] also showed clinical efficacy. Again, if you look at the tumors that had no PD-L1 expression, the clinical efficacy seemed to favor the addition of a CTLA-4 antibody to this group.

1:57 | Finally, CheckMate-9LA [NCT03215706] had a very similar approach to cycles of chemotherapy with nivolumab [Opdivo] and ipilimumab [Yervoy] and again, if you look at the overall survival data that's been sort of reported thus far, PD-L1-negative tumors do seem to benefit from that combination. The idea here is that we don't really have randomized phase 3 trials to guide us, but looking at the subgroup analysis of the studies, it is possible that a combination of a CTLA-4 antibody with a checkpoint inhibitor with or without chemotherapy can be useful.