Granisetron transdermal delivery system for nausea and vomiting prophylaxis in HER2-positive metastatic breast cancer patients receiving pyrotinib and capecitabine: A single-arm phase II study.

Abstract

12069 Background: The efficacy of granisetron transdermal delivery system (GTDS) in managing nausea and vomiting caused by intravenous chemotherapy is well-established; however, its effectiveness for emesis induced by oral antineoplastic agents remains unclear. This study aimed to evaluate the efficacy and safety of GTDS for the prophylaxis of nausea and vomiting in patients receiving daily oral anticancer agents with moderate emetic risk, specifically pyrotinib combined with capecitabine for HER2-positive metastatic breast cancer (mBC). Methods: A single-arm, single-center phase II trial was conducted, enrolling 77 patients with HER2-positive mBC. Patients received 2 consecutive doses of GTDS (with a 7-day interval between the doses) during the first treatment cycle (21 days) of pyrotinib (400 mg daily, days 1–21) and capecitabine (1000 mg/m² twice daily, days 1–14). The dual primary endpoints were the complete response (CR) rate of nausea and vomiting (no emesis and no rescue medication) and the incidence of ≥grade 3 diarrhea. Secondary endpoints included complete control (CC) rate, daily emesis/nausea frequency and adverse events (AEs). Results: During the first treatment cycle, 62.3% of patients achieved CR, and the CC rate was 54.5%. Weekly CR rates were 79.2%, 70.1%, and 79.2% in weeks 1, 2, and 3, respectively, while CC rates were 72.7%, 61.0%, and 70.1%, respectively. The mean daily number of emetic episodes ranged from 0.1 to 0.6, peaking in week 2. The mean daily nausea scores ranged from 0.6 to 1.1, with a slight increase starting from day 4. Grade 3 diarrhea occurred in 28.6% of patients, peaking on day 7. AEs were reported in 53.25% of patients, with the most common being gastrointestinal symptoms, fatigue, and rash. No QT prolongation was observed. Conclusions: Prolonged administration of GTDS demonstrated efficacy and safety in preventing nausea and vomiting in HER2-positive mBC patients receiving daily oral pyrotinib and capecitabine; however, it did not reduce the incidence of ≥ grade 3 diarrhea. Clinical trial information: NCT04472143 .