A multicenter, phase II trial conducted in Japan has demonstrated promising results for a triplet antiemetic therapy in preventing chemotherapy-induced nausea and vomiting (CINV) in patients undergoing highly emetogenic chemotherapy (HEC) for breast cancer. The study, which involved eight domestic institutions, investigated the efficacy and safety of combining palonosetron, aprepitant, and olanzapine (PALO, APR, and OLN) to improve CINV control.
The trial enrolled patients scheduled to receive their initial HEC treatment, specifically regimens like AC (doxorubicin + cyclophosphamide), EC (epirubicin + cyclophosphamide), CAF, FEC, and TAC. These regimens are known for their high emetogenic potential, often leading to significant nausea and vomiting despite standard antiemetic prophylaxis. The primary endpoint was the total control (TC) rate of nausea and vomiting throughout the overall phase (0-120 hours after chemotherapy), defined as the absence of nausea, vomiting, and the use of rescue medication.
Study Design and Patient Population
The study included patients aged 20 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Exclusion criteria included a history of allergy to the study drugs, steroid use (excluding inhaled/topical), evident vomiting symptoms, gastrointestinal disorders, seizure disorders, and pregnancy. Patients received PALO 0.75 mg intravenously, OLN 5 mg orally once daily from day 0 to day 4, and APR 125 mg orally on day 1 followed by 80 mg on days 2 and 3, or fosaprepitant 150 mg intravenously on day 1.
Key Findings
The primary endpoint of the study was the total control (TC) rate of nausea and vomiting throughout the overall phase (0–120 h after chemotherapy), defined as the absence of nausea, vomiting, and the use of rescue medication. Secondary endpoints included the TC rate during the acute phase (0–24 h after chemotherapy) and the delayed phase (24–120 h after chemotherapy), CR of vomiting, complete control (CC) of nausea and vomiting, and the proportions of “no nausea” during the acute phase, delayed phase, and overall phase.
Rationale for Triplet Therapy
The rationale behind the triplet therapy lies in addressing both acute and delayed phases of CINV. Palonosetron, a 5-HT3 receptor antagonist, is effective in controlling acute CINV. Aprepitant, an NK-1 receptor antagonist, helps manage delayed CINV. Olanzapine, an atypical antipsychotic with antiemetic properties, has shown promise in further reducing CINV when added to standard regimens. The study also considered the potential impact of pre-chemotherapy insomnia on CINV, administering OLN before bedtime on the day before chemotherapy to potentially mitigate this effect.
Implications for Clinical Practice
These findings suggest that the triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine could offer improved CINV control for breast cancer patients undergoing HEC. Further research, including larger randomized controlled trials, is warranted to confirm these results and establish the optimal use of this triplet regimen in clinical practice.
