Fosrolapitant/Palonosetron in Chemotherapy-Induced Nausea and Vomiting
1. The complete response rate at the overall phase in cycle 1 was 77.7% vs 78.2% with treatment vs control groups (significant for noninferiority).
2. Treatment-related adverse events in the overall study were 42.1% in the treatment group and 44.0% in the control group.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Chemotherapy-induced nausea and vomiting (CINV) pose significant challenges to patient well-being and oncologic treatment. This is especially true with Cisplatin-based chemotherapy as it is a highly emetogenic chemotherapy (HEC) with suboptimal adherence to antiemetic regimens. This trial examined HR20013, a novel combination of rolapitant (an NK-1 RA) and palonosetron (a 5-HT3 RA) against standard triple therapy in patients receiving highly emetogenic chemotherapy. The primary endpoint was complete response (CR, no emesis and no rescue therapy) rate in the overall phase (0-120h after HEC in cycle 1), and secondary endpoints included CR at various other time points, time to treatment failure (TTF), and quality of life (QoL). The CR rate at the overall phase in cycle 1 was 77.7% vs 78.2% with treatment vs control groups (significant for noninferiority). The CR rate beyond the delayed phase in cycle 1 (120-168h) was 90.3% vs 86.5% with treatment vs control groups (non-significant for superiority). CR rates between the two groups were similar in the acute (0-24h), delayed (24-120h), and total (0-168h) phase in cycle 1, and were similar in all time points in cycle 2. The median TTF was not reached for either group in either cycle and the HR for TTF was 0.87 (non-significant) in cycle 1 and 0.84 (non-significant) in cycle 2. With regards to safety, treatment-related adverse events in the overall study were 42.1% in the treatment group and 44.0% in the control group with the most common events being constipation (10.7% in the treatment group vs 14.3% in the control group) and hiccups (7.5% vs 11.4%). Most events were grade 1 or 2, with grade ≥3 occurring in 3.8% in the treatment group and 3.4% in the control group. With regards to QoL, there was no difference between groups in cycle 1, however, cycle 2 found some minor but statistically significant improvements in the treatment group compared to the control group at the delayed phase and in the beyond delayed phase. The strengths of this study included its sample size, and the limitations included the study duration and focus on a single chemotherapy regimen. Overall, this study found that HR20013+dexamathasone was non-inferior to standard triple therapy for preventing CINV in patients receiving HEC.
Click to read the study in JCO
In-Depth [randomized controlled trial]: This Chinese multicenter, double-blind, phase III trial enrolled adults with confirmed malignant solid tumors, with no prior chemotherapy, who were scheduled to receive the single-day cisplatin-based chemotherapy, and randomized them (1:1) to HR20013 + dexamethasone (treatment group, n=375) vs fosaprepitant + palonosetron + dexamethasone (control group, n=379). Most patients were male (69.9%), and had lung cancer (52.7%). The CR rate at the overall phase in cycle 1 was 77.7% vs 78.2% with treatment vs control groups (difference = -0.9% [95%CI, -6.7 to 5.0], p<0.01 for noninferiority). The CR rate beyond the delayed phase in cycle 1 (120-168h) was 90.3% vs 86.5% with treatment vs control groups (difference = 3.7% [95%CI, -0.9 to 8.2], p=0.11 for superiority). CR rates between the two groups were similar in the acute (0-24h), delayed (24-120h), and total (0-168h) phase in cycle 1, and were similar in all time points in cycle 2. The median TTF was not reached for either group in either cycle and the HR for TTF was 0.87 (95%CI, 0.64-1.17, p=0.35) in cycle 1 and 0.84 (95%CI, 0.61-1.17, p=0.31) in cycle 2. With regards to safety, treatment-related adverse events in the overall study were 42.1% in the treatment group and 44.0% in the control group with the most common events being constipation (10.7% in the treatment group vs 14.3% in the control group) and hiccups (7.5% vs 11.4%). Most events were grade 1 or 2, with grade ≥3 events occurring in 3.8% in the treatment group vs 3.4% in the control group. With regards to QoL, there was no difference between groups in cycle 1, however, cycle 2 found some minor but statistically significant improvements in the treatment group compared to the control group at the delayed phase and in the beyond delayed phase. Overall, this study found that HR20013+dexamathasone was non-inferior to standard triple therapy for preventing CINV in patients receiving HEC.
Image: PD
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