Nivolumab plus Ipilumumab in NSCLC: A New Use for Tumor Mutational Burden?
Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med 2018 Apr 16.
In the future, researchers will need to compare these agents to the new standard of care. Chemotherapy as a control arm no longer is appropriate in a majority of patients. Some patients in this study were PD-L1 greater than 50% and TMB greater than 10; for them, the control should be pembrolizumab. In addition, sequencing therapy continues to be a challenge. Finally, studies in patients with other malignancies have looked at shorter courses of ipilimumab with reduced toxicity with similar benefit [6], and this could be applied to lung cancer as well.
Application for Clinical Practice
This trial adds an additional actionable target to the array of treatments for NSCLC. In patients with newly diagnosed metastatic non-squamous NSCLC with no actionable EGFR or ALK mutation and PD-L1 less than 50%, testing for TMB on tumor should be performed. If the test shows 10 or greater mutations per megabase, combination nivolumab and ipilimumab should be offered over standard chemotherapy. Special consideration of patient characteristics to determine candidacy and tolerability of this treatment should be evaluated.
— Jacob Elkon, MD, George Washington University School of Medicine, Washington, DC
