RESUMEN
Background: Trastuzumab deruxtecan is classified as an anticancer agent that poses a moderate emetic risk in the international guidelines for antiemetic therapy. The guidelines recommend emesis prophylaxis using a two-drug combination therapy comprising a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone (DEX). However, the high incidence of nausea and vomiting associated with trastuzumab deruxtecan is problematic. The National Comprehensive Cancer Network guideline version 1.2023 classified trastuzumab deruxtecan as having a high risk of emesis and changed its recommendation to a triplet regimen including a neurokinin-1 receptor antagonist (NK1RA). However, the emetogenic potential of trastuzumab-deruxtecan and the optimal antiemetic prophylaxis are controversial. Hence, this exploratory phase 2 study aimed to assess the efficacy and safety of treatment comprising 5-HT3RA and DEX with or without a NK1RA in preventing trastuzumab deruxtecan-induced nausea and vomiting. Methods: We conducted an open-label and randomized exploratory phase 2 study at 14 centers in Japan. Patients with breast cancer who were scheduled to receive trastuzumab deruxtecan were enrolled in this study. The patients were randomly assigned to receive granisetron and DEX (arm GD) or granisetron, DEX, and aprepitant (fosaprepitant; arm GDA). The primary endpoint was complete response (CR; no emesis or no rescue therapy) during the overall phase (120 h after the start of trastuzumab deruxtecan). Results: Between September 2020 and March 2023, 40 patients were randomly assigned to the GD (n = 19) or GDA (n = 21) arm. In the GDA arm, one patient who did not complete the use of the rescue medication listed in the diary was excluded from the efficacy analysis, which included the use of rescue medication. The CR rates during the overall phase were 36.8% and 70.0% in the GD and GDA arms, respectively (odds ratio 0.1334; 95% confidence interval [CI]: 0.0232-0.7672; P = 0.0190), with a difference of 33.2%. No grade 3 or 4 toxicity related to antiemetic therapy was observed. Conclusions: Patients receiving trastuzumab deruxtecan require triple therapy, including mandatory NK1RA administration.
RESUMEN
The association between capecitabine efficacy and proton pump inhibitors (PPIs) is controversial. Here, we determined whether co-administration of PPIs affects the real-world effectiveness of capecitabine. This retrospective observational study included consecutive patients with stage II-III colorectal cancer (CRC) who received adjuvant capecitabine monotherapy or CapeOX (capecitabine and oxaliplatin) between January 2009 and December 2014 at nine participating institutions. The primary endpoint was the difference in relapse-free survival (RFS) between patients who received PPIs and those who did not and was estimated using the Kaplan-Meier method. Overall survival (OS) was the secondary endpoint. Multivariable analysis of RFS and OS was performed using a Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting (IPTW) analyses. Data from 606 patients were evaluated, 54 of whom had received a PPI. PPI-treated patients tended to have poorer RFS and OS than patients treated without PPIs. The hazard ratio for RFS with capecitabine monotherapy was 2.48 (95% confidence interval: 1.22-5.07). These results were consistent with sensitivity analyses performed using propensity score adjustment and IPTW methods. Co-administration of PPIs may reduce the effectiveness of capecitabine and negatively impact patients with stage II-III CRC.