Immune Checkpoint Inhibitor Combinations in NSCLC

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Immune checkpoint inhibitors, such as nivolumab, are being explored in combination with targeted therapies and chemotherapies as treatments for patients with non-small cell lung cancer (NSCLC). As with any combination, higher rates of certain side effects were observed in these trials, suggests Mark G. Kris, MD. Even when combining two immune checkpoint inhibitors, such as ipilimumab and nivolumab, additional side effects are manifested. To avoid these adverse events, sequential administration could still be beneficial, suggests Kris.

The average patient with lung cancer is 71 years old with several comorbidities, notes Mark A. Socinski, MD. Especially in these patients, there is a need to closely monitor the side effects associated with immune checkpoint inhibition. This is especially true when considering combinations, Socinski.

As a result of the efficacy seen with these agents, checkpoint inhibitors are being explored across a number of settings for patients with NSCLC, including earlier stage locally advanced lung cancer and in the adjuvant setting. However, Socinski warns, most of the optimism at this point is based on early clinical trials. Large randomized trials have not yet been completed in lung cancer.

In general, corticosteroids are often administered to alleviate many of the immune-related side effects associated with treatment, notes Kris. For severe steroid-refractory treatment-induced colitis, Kris recommends the administration of the TNF-alpha inhibitor infliximab, which is commonly used to treat ipilimumab-associated colitis. Moreover, Kris cautions, since the immune checkpoint inhibitors are antibodies, corticosteroids should be administered for several months in order to adequately control side effects, such as nephritis and pneumonitis.

Tolerability is a big concern, particularly when treating patients with advanced stage NSCLC, notes Benjamin P. Levy, MD. When investigating these treatments, tolerability should be considered to be just as important as efficacy.