Greater Depth of Response to Therapy Improves Survival in Non-small Cell Lung Cancer

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Researchers examined the effects of ALK inhibitors and programmed cell death-1 inhibitors in NSCLC.
Researchers examined the effects of ALK inhibitors and programmed cell death-1 inhibitors in NSCLC.

A greater depth of response (DepOR) to therapy was associated with prolonged overall survival (OS) and progression-free survival (PFS) for patients with non-small cell lung cancer (NSCLC) and may have clinical utility as an outcome measure of treatment efficacy, according to a study published in the Annals of Oncology.

With therapies such as ALK inhibitors (ALKi) and programmed cell death-1 (PD-1) inhibitors advancing rapidly, established methods of treatment efficacy may no longer be sufficient. DepOR, which measures the percent of maximal tumor reduction from baseline, may provide faster insights to the clinical efficacy of study treatments compared with the standard time-to-event outcome measurements such as PFS and OS.

For this retrospective analysis, the authors studied the results of 2 randomized controlled trials for ALKi and 2 for anti-PD-1.

For the ALKi studies, patients who responded to therapy were divided into quartiles based on the extent of DepOR. Researchers discovered that there were marked improvements in OS as the DepOR quartiles increased. Only the third (hazard ratio [HR], 0.28; 95% CI, 0.11-0.73) and fourth quartiles (HR 0.05; 95% CI, 0.01-0.28) were associated with significant benefit. All quartiles demonstrated a significant association between DepOR and PFS.

In the PD-1 studies, there was a similar relationship between DepOR and PFS and OS. Unlike the ALKi studies, where corresponding gains in PFS and OS were seen with each quartile, significant differences were only observable when grouping patients as those with greater than 50% reduction in tumor burden and those with 50% or less reduction in tumor burden.

The authors concluded that DepOR may be a useful clinical end point for early evaluation in emerging therapies, but that “prospective evaluations are needed to understand how to use DepOR as an end point in clinical trials and how it compares to the traditional RECIST measures of tumor response.”

Reference

McCoach CE, Blumenthal GM, Zhang L, et al. Exploratory analysis of the association of depth of response and survival in patients with metastatic non-small cell lung cancer treated with a targeted therapy or immunotherapy [published online August 2, 2017]. Ann Oncol. doi:10.1093/annonc/mdx414

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