1821MO - Predictive biomarkers of dyspnea response to dexamethasone in cancer patients: A secondary analysis of the Alleviating Breathlessness in Cancer Patients with Dyspnea (ABCD) trial

Background

In the Alleviating Breathlessness in Cancer Patients with Dexamethasone (ABCD) trial (Hui et al. Lancet Oncol 2022), we found that dexamethasone improved dyspnea but not more than placebo in unselected patients with cancer. In this pre-planned secondary analysis, we examined the predictive utility of cytokines for dyspnea response.

Methods

We performed a secondary analysis of the ABCD trial, a double-blind, randomized clinical trial comparing high-dose dexamethasone to placebo. The primary outcome was dyspnea intensity, assessed over 14 days. Blood cytokine levels (TNF, IL-6, IL-8, and IL-10) were measured at baseline, day 7, and day 14. We used a generalized additive model (GAM) to examine the association between baseline cytokine level and change in dyspnea from baseline to day 7 and baseline to day 14 in dexamethasone and placebo groups.

Results

Of the 128 patients from the ABCD trial, 45 provided blood samples. TNF, IL-6, and IL-8 decreased significantly over 14 days in the dexamethasone group but not placebo (Table). Lower baseline TNF was significantly associated with a greater reduction in dyspnea intensity by day 7 in the placebo group (p=0.0013); conversely, higher baseline TNF was associated with a greater reduction in dyspnea intensity by day 7 in the dexamethasone group (difference between groups p=0.0019). Similar patterns were observed for IL-6 (p=0.000051), IL-8 (p=0.00063), and IL-10 (p=0.01) on day 7, and all 4 cytokines on day 14. Table. Changes in inflammatory biomarker levels between treatment groups. Table: 1821MO

Conclusions

Cytokines decreased with dexamethasone, but not placebo. Higher baseline cytokine levels may identify patients more likely to respond to dexamethasone and less likely to respond to placebo. Our findings may have implications for how predictive biomarkers can be used to inform more personalized supportive treatments.

Clinical trial identification

NCT03367156.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Cancer Institute (R01 CA214960-01).

Disclosure

All authors have declared no conflicts of interest.