N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP)—A Prognostic Biomarker in Older and/or Frail Adults with Advanced Gastroesophageal Cancer: A Post Hoc Analysis of the GO2 Clinical Trial

<b>Background:</b> Better prognostic biomarkers are needed in older adults with cancer. There are established links between N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) and sarcopenia, and sarcopenia is associated with poorer cancer survival. However, there are limited data regarding baseline NT-proBNP as a biomarker of cancer outcome. The GO2 trial recruited older and/or frail United Kingdom (UK) patients with advanced gastroesophageal cancer and investigated the role of chemotherapy dose de-escalation. Using the GO2 database, we sought to investigate the prognostic role of NT-proBNP as well as the interaction between NT-proBNP and frailty. <b>Methods:</b> This was a post-hoc analysis of a completed clinical trial. Frailty measures included ECOG performance status (PS) and GO2 frailty grouping (based on an assessment of nine geriatric domains). A corrected NT-proBNP (cBNP) was calculated for each patient, adjusting for the upper limit of normal (ULN) reference from each centre. <b>Results:</b> A total of 241 patients were eligible to be included in the analysis. The median age was 76 (range 52-89), 187 (77.6%) were male and 211 (87.6%) had adenocarcinoma. Eighty (33.2%) patients had a baseline NT-proBNP above the local ULN. There was no association between cBNP and ECOG PS (<i>p</i> = 0.36) or the GO2 frailty group (<i>p</i> = 0.58). Those with the highest cBNP (<i>n</i> = 59) had significantly inferior median overall survival: 5.3 months (mos.) vs. 6.8 mos. (medium, <i>n</i> = 120) vs. 8.2 mos. (low, <i>n</i> = 61); HR 1.57 (95% CI; 1.04-2.37), <i>p</i> = 0.031. This was maintained on a Cox regression analysis (HR 1.69, <i>p</i> = 0.01) accounting for the GO2 trial stratification factors. There was no clear association between frailty and NT-proBNP. <b>Conclusions:</b> In this study, NT-proBNP appeared to be prognostic-independent of other factors. Further investigation and validation are needed to confirm our findings and to determine the potential beneficial role of cardioprotective therapy in at-risk patients with cancer identified in this manner.