Clinical outcome and prognostic factors for Asian patients in Phase I clinical trials

Abstract

Background: Patient selection is key in Phase I studies, and prognosis can be difficult to estimate in heavily pre-treated patients. Previous prognostic models like the Royal Marsden Hospital (RMH) score or using the neutrophil–lymphocyte ratio (NLR) have not been validated in current novel therapies nor in the Asian Phase I population. Methods: We conducted a retrospective review of 414 patients with solid tumours participating in Phase I studies at our centre between October 2013 and December 2020. Results: The RMH model showed poorer prognosis with increasing scores [RMH score 1, HR 1.28 (95% CI: 0.96–1.70); RMH score 2, HR 2.27 (95% CI: 1.62–3.17); RMH score 3, HR 4.14 (95% CI: 2.62–6.53)]. NLR did not improve the AUC of the model. Poorer ECOG status (ECOG 1 vs. 0: HR = 1.59 (95% CI = 1.24–2.04), P < 0.001) and primary tumour site (GI vs. breast cancer: HR = 3.06, 95% CI = 2.16–4.35, P < 0.001) were prognostic. Conclusions: We developed a NCIS prognostic score with excellent prognostic ability for both short-term and longer-term survival (iAUC: 0.71 [95% CI 0.65–0.76]), and validated the RMH model in the largest Asian study to date.