Netupitant-palonosetron combined with dexamethasone for preventing chemotherapy-induced nausea and vomiting in high-risk patients with colorectal cancer receiving moderately emetogenic chemotherapy: A retrospective study.

Although netupitant-palonosetron (NEPA) is an established option for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy, its efficacy in patients with high-risk features undergoing moderately emetogenic chemotherapy (MEC) remains insufficiently investigated. Therefore, the present study evaluated the efficacy of NEPA combined with dexamethasone for preventing CINV in high-risk patients with colorectal cancer (CRC) receiving MEC. This retrospective analysis included 182 patients with CRC receiving MEC who had at least one high-risk factor for CINV, including no alcohol consumption, a history of CINV and female sex. All patients received prophylaxis with a single dose of NEPA combined with dexamethasone. The primary outcome was complete remission (CR), defined as no vomiting and no rescue medication use. Secondary outcomes included complete control (CC), defined as no significant nausea, no vomiting and no rescue medication use, and complete protection (CP), defined as no nausea, no vomiting and no rescue medication use, assessed during the acute (0-24 h), delayed (24-120 h) and overall (0-120 h) phases. Extended efficacy during the 120-168 h period and safety outcomes were also evaluated. The median age was 58.7 years (range: 32-75 years). The most frequent high-risk factors were no alcohol consumption (72.0%, 131/182) and a history of CINV (22.0%, 40/182). CR rates during the acute, delayed and overall phases were 98.9, 95.6 and 94.5%, respectively. CC rates were 98.9, 92.3 and 91.2% in the acute, delayed, and overall phases, respectively, while CP rates were 98.9, 78.0 and 76.3% in the corresponding phases. Although CR rates >95% in the acute and delayed phases and only 1.1% of patients required rescue therapy, the CP rate markedly declined from 98.9% in the acute phase to 78.0% in the delayed phase, indicating that nausea control remains a major clinical challenge during the delayed period despite effective prevention of vomiting. In a subset of 120 patients, the overall CR, CC and CP rates during the 120-168 h post-chemotherapy period remained high at 96.6, 91.6 and 84.2%, respectively. The combination of NEPA and dexamethasone was well tolerated; constipation was the most frequently reported adverse event (11.0%), predominantly grade 1 (9.3%), with no grade 3 or 4 events observed. In this single-arm retrospective study, the combination of NEPA and dexamethasone demonstrated promising efficacy and a favorable safety profile in high-risk patients with CRC receiving MEC, with sustained antiemetic protection beyond 120 h post-chemotherapy. Nevertheless, these findings should be considered preliminary and require confirmation in prospective randomized controlled trials.