Immune Checkpoint Inhibitors in NSCLC

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The substantial benefits derived from treatment with immune checkpoint inhibitors could have the most meaningful impact in non-small cell lung cancer (NSCLC), believes Louis M. Weiner, MD. Effective treatments are desperately needed for this type of cancer, as the death rate from this disease is among the highest in the world.

The PD-1 and PD-L1 inhibitors have consistently demonstrated responses in the 20% to 25% range, notes Mark A. Socinski, MD. However, the duration is the most impressive aspect of these responses, as they tend to be long lasting.

The median age of patients with NSCLC is 71 with the existence of comorbidities, which places further importance on toxicity, notes Socinski. Without phase III data, it is difficult to compare the efficacy and toxicity between PD-1 and PD-L1-targeted agents in NSCLC, notes Roy S. Herbst, MD. However, targeting PD-L1 directly rather than PD-1 leaves PD-L2 intact. This prevents some side effects, such as colitis and pneumonitis, Herbst notes.

Biomarker analyses for patient selection remain unclear for these agents, Herbst notes. Trials have selected patients based on PD-L1 status with varying results. Responses are higher in PD-L1-positive patients; however, those with PD-L1-negative disease still respond to therapy.

Traditionally, the most effective approaches involve the combination of several therapies. However, combination strategies could be more difficult to find in NSCLC, since the population is older with more comorbidity, Herbst notes. For some patients (20% to 25%), the immune checkpoint inhibitor alone seems sufficient, Weiner notes. At this point, finding the patients who require further treatment remains an unmet need.