Checkpoint Inhibitor Related Pseudoprogression in NSCLC

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Pseudoprogression is common following treatment with checkpoint inhibitors, such as nivolumab or ipilimumab. In this phenomenon, apparent tumor growth is followed by sustained tumor regression, possibly as a result of delayed immune activity and subsequent edema, notes Benjamin P. Levy, MD. To account for pseudoprogression, a novel endpoint known as immune-related progression-free survival was developed for clinical trials exploring checkpoint inhibitors in non-small cell lung cancer (NSCLC).

Measuring actual progression in patients taking checkpoint inhibitors can be challenging as a result of this false progression, suggests Levy. In general, 50% of patients treated with nivolumab respond within 8 weeks, and initial progression should not be grounds for treatment discontinuation with checkpoint inhibitors, Levy notes.

Progression in these clinical trials is being measured by RECIST criteria, which is not applicable outside of a clinical trial, states Mark G. Kris, MD. If a patient is benefiting from treatment then therapy should not be discontinued, regardless of what scans indicate, Kris believes.

In some circumstances, tumors may double in size before they begin to respond to treatment with checkpoint inhibitors, notes Heather A. Wakelee, MD. However, following approximately 2 months of treatment, these tumors begin to shrink. Interestingly, the patients who experienced the greatest initial tumor growth seemed to have the most durable responses, Wakelee notes.

Outside of pseudoprogression, patients seem to respond to treatment regardless of histology, although these responses seem to be higher in patients with squamous NSCLC, Wakelee notes. As research continues, a connection between histology and a biomarker may emerge, Wakelee hopes. However, at this point, she feels the drug is still too early in its development to begin excluding patients.