Foreword
The 2024 Joint Annual Meeting of the International Society for Supportive Care of Cancer and the International Society of Oral Oncology (MASCC/ISOO) was successfully held in Lille, France from June 27 to 29, 2024. As a high-level conference in the field of supportive care for oncology, this conference focuses on the latest global progress in supportive care for oncology.
Led by Professor Zhang Zhang of the Cancer Center of Sun Yat-sen University and jointly participated by 68 research centers across the country, the results of the "Evaluation of the Efficacy and Safety of HR20013 for Injection in the Prevention of Nausea and Vomiting Caused by Hyperemetic Chemotherapy - Multicenter, Randomized, Double-blind and Double-Simulation, Active-Controlled Phase III Clinical Study (PROFIT)" were released at the conference. The results of the study showed that compared with fosaprepitant + palonosetron + dexamethasone (FAPR+PALO+DEX), for patients receiving hyperemetogenic chemotherapy (HEC), HR20013 + dexamethasone (DEX) has the potential to improve QoL, especially in the delayed and ultra-delayed phases.
Professor Zhang Zhang made a short speech on the poster at the conference
Background:
According to the latest data, there are 4,824,700 new cases of malignant tumors and 2,574,200 deaths in mainland China every year1. The comprehensive prevention and control of malignant tumors is still a problem that we need to face at present. In recent years, new anti-tumor treatment regimens and drugs have been developed, but nausea and vomiting associated with anti-tumor therapy are still common adverse reactions. In particular, chemotherapy-induced nausea and vomiting (CINV) can make patients fear chemotherapy, reduce patient compliance, and then affect patients' survival benefits. Serotonamide 3 receptor (5-HT3 RA) and neurokinin receptor 1 (NK-1 RA) play a key role in the pathogenesis of CINV2. HEC, represented by cisplatin, causes an incidence of acute vomiting > 90%. At present, domestic and foreign guidelines for the prevention of HEC-associated CINV recommend a triple/quadruple regimen based on serotonin 3 receptor antagonist (5-HT3 RA) and neurokinin receptor 1 antagonist (NK-1 RA)2-3. However, in practice, the prevention of HEC-associated CINV is cumbersome and has low adherence. How to simplify clinical medication management and improve patients' medication compliance and guideline compliance is still a problem that needs to be further solved.
HR20013 is a class I new drug independently developed by Jiangsu Hengrui Pharmaceutical Co., Ltd., and the first batch of indication marketing applications have been accepted by CDE. HR20013 is a hybrid formulation of HRS5580 (a novel NK-1 antagonist) and palonosetron (the only second-generation 5-HT3 antagonist), and is a novel ultra-long-acting antiemetic product that can antagonize both NK-1 and 5-HT3 receptors to exert antiemettic effects. HR20013 only needs to be administered once per cycle, which greatly simplifies medication management and takes into account safety, effectiveness and compliance.
Research Methods:
This study is a multicenter, randomized, double-blind, double-dummy, active-controlled phase III clinical trial, a total of 754 patients with malignant solid tumors who have not undergone chemotherapy (750 patients received drug therapy) were randomly divided into two groups, and before each cycle of cisplatin-based hyperemetic chemotherapy (a total of 2 cycles), they were treated with either HR20013 or fosaprepitant + palonosetron (FAPR+PALO), and oral DEX (D1-D4). Primary Endpoint: Proportion of subjects with complete remission (CR) in the overall phase (0-120h) after initiation of cisplatin administration in the first cycle of chemotherapy. The study design is shown in Figure 1. The primary endpoint has been met, and efficacy data have been presented at the 2024 World Conference on Lung Cancer (WCLC). This conference mainly introduces patient QoL data. The endpoints related to QoL were the change in Vomiting Life Function Scale (FLIE) score and the proportion of patients with no impact on daily living (NIDL) reported in Cycle 1 and Cycle 2. FLIE questionnaires were administered at baseline, 24, 120, and 168 hours after the start of HEC. NIDL is defined as an overall FLIE score >108; or nausea/vomiting score >54.
Figure 1: Study design diagram
Findings:
Baseline characteristics were comparable between the two groups. There were 373 and 377 patients in the HR20013+DEX and FAPR+PALO+DEX groups receiving the first cycle of study treatment, and 314 and 336 patients receiving the second cycle of study treatment, respectively.
In Cycle 1, there was no statistically significant difference from baseline in global/nausea/vomiting FLIE scores between the two groups (all P>0.05; Figure 2). In cycle 2, HR20013+DEX compared to FAPR+PALO+DEX, the total score in the delay period (24-120 h; The mean LS was -3.5 vs 6.0, respectively; P=0.03), delayed vomiting score (-1.2 vs -2.4; P=0.03), nausea score in the ultra-delayed period (120-168 h; -1.1 vs -2.1; P=0.04) compared with baseline (Fig. 3).
Figure 2 (left) Change in FLIE score in Cycle 1: total score (A), nausea score (B), and vomiting score (C)
Figure 3 (right) Change in FLIE score in Cycle 2: total score (A), nausea score (B), and vomiting score (C)
In Cycle 1, the proportion of patients with NIDL reported in all three groups [acute, delayed, and ultra-delayed] was approximately equivalent in the global, nausea, and vomiting domains (all P>). 0.05; Figure 4). In cycle 2, the HR20013+DEX group compared with the FAPR+PALO+DEX group had a significant global domain delay period (93.6% versus 87.8%; P=0.01), delayed vomiting domain (95.2% vs 90.8%; P=0.03), the overall domain over-delay period (96.8% vs 92.9%; P=0.03), nausea domain hyperdelay period (95.9% vs 91.1%; P=0.02) NIDL patients reported a higher proportion (Fig. 5).
Fig.4 Proportion of patients reporting NIDL based on FLIE score in Cycle 1
Fig.5 Proportion of patients reporting NIDL based on FLIE score in Cycle 2
conclusion
Compared with FAPR+PALO+DEX, HR20013+DEX has the potential to improve patient QoL for patients undergoing HEC, especially in the delayed and ultra-delayed phases.
Expert Profile
Professor Zhang Li
- Sun Yat-sen University Cancer Center, Director of the Department of Internal Medicine, Ph.D. supervisor, second-level professor, chief expert of lung cancer
- Honorary Chairman of the Cancer Rehabilitation and Palliative Care Committee of the Chinese Anti-Cancer Association (CACA).
- He is the chairman-elect of the Oncology Drug Clinical Research Committee of the Chinese Anti-Cancer Association (CACA).
- Executive Director of the Chinese Society of Clinical Oncology (CSCO).
- He is the chairman-elect of the Immunotherapy Expert Committee of the Chinese Society of Clinical Oncology (CSCO).
- Vice Chairman of the Non-Small Cell Lung Cancer Expert Committee of the Chinese Society of Clinical Oncology (CSCO).
- Vice Chairman of the Expert Committee of Tumor Support and Rehabilitation Therapy of the Chinese Society of Clinical Oncology (CSCO).
- Chairman of the Clinical Research Branch of Guangdong Medical Association
- Chairman of the Precision Medicine Branch of Guangdong Clinical Medical Association
Bibliography:
1.Zheng RS,Chen R,Han BF,et al.[Cancer incidence and mortality in China, 2022]. Zhonghua Zhong Liu Za Zhi.2024 Mar 23; 46(3):221-231.
2.Antiemesis,NCCN Guidelines,2024 V1.
3.China Anti-Cancer Association Committee of Rehabilitation and Palliative Care; China Anti-Cancer Association Committee of Tumor Clinical Chemotherapy; China Anti-Cancer Association Committee of Neoplastic Supportive-Care; Chinese Society of Clinical Oncology Committee of Supportive and Rehabilitative Care. [China guidelines on prevention and treatment of nausea and vomiting caused by antitumor therapies (2023 edition)]. Zhonghua Zhong Liu Za Zhi. 2024 Jun 23; 46(6):481-501.
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