Efficacy and safety of mixed formulation aprepitant and palonosetron (QLM2010) for prevention of cisplatin-based highly emetogenic chemotherapy-induced nausea and vomiting: A multicenter, randomized, double-blind, double-dummy, positive-controlled phase III study.

Abstract

12147 Background: QLM2010, a novel fixed-dose intravenous antiemetic combination of aprepitant and palonosetron (PALO), can simultaneously antagonize 5-hydroxytryptamine-3 and neurokinin-1 receptors. This study aimed to assess the efficacy and safety of QLM2010 plus dexamethasone (DEX) versus fosaprepitant (FAPR) combined with PALO and DEX for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC). Methods: This was a multicenter, randomized, double-blind, double-dummy, positive-controlled Phase III trial. Chemotherapy-naïve patients with solid tumors were randomly assigned 1:1 to receive QLM2010 (Day 1) or FAPR + PALO (Day 1) prior to cisplatin-based HEC, together with oral DEX (Days 1–4). The primary efficacy endpoint was complete response (CR: no emesis/no rescue medication) during the overall (0–120 hours) phase. Results: Baseline demographic and clinical characteristics were well-balanced between the two groups (QLM2010 group: n = 329; FAPR+PALO group: n = 331). The overall CR rate was 82.67% versus 80.97% (risk difference, 1.65%; 95% CI, −4.21–7.50%), confirming the non-inferiority of QLM2010 + DEX to FAPR + PALO + DEX. CR rates in both the acute (0–24 hours) and delayed (24–120 hours) phases were comparable between groups. Across all phases, the QLM2010 group showed similar rates to the FAPR+PALO group for no emesis, no nausea, no significant nausea, no rescue therapy, and complete protection (all P > 0.05). Notably, QLM2010 + DEX showed greater proportions of patients reporting no impact on daily life on Day 2 after treatment compared with FAPR + PALO + DEX (P = 0.0279). A single injection-site reaction (0.30 %) was confined to the FAPR+PALO group; none was observed in the QLM2010 group. The incidence of hiccups was numerically lower in the QLM2010 group compared with the FAPR+PALO group (8.2% vs. 15.1%). Conclusions: QLM2010 + DEX was non-inferior to FAPR + PALO + DEX for preventing CINV in cisplatin-based HEC patients and well tolerated, with the potential to reduce the impact of CINV on daily life. QLM2010 furnishes a novel, more convenient therapeutic alternative for the clinical management of CINV. Clinical trial information: NCT07081256 .