Netupitant/palonosetron (NEPA) and dexamethasone for prevention of emesis in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide: a multi-cycle, phase II study

Abstract

Background: NEPA is an oral fixed-dose combination of netupitant, a new highly selective neurokinin-1 receptor antagonist, and palonosetron. This study was conducted to evaluate whether the efficacy of NEPA against chemotherapy-induced nausea and vomiting (CINV) in cycle 1 would be maintained over subsequent chemotherapy cycles in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide (AC). The study also describes the relationship between efficacy on day 1 through 5 (overall period) and control of CINV on day 6 through 21 (very late period) in each cycle. Methods: In this multicentre, phase II study, patients received both NEPA and dexamethasone (12 mg intravenously) just before chemotherapy. The primary efficacy endpoint was overall complete response (CR; no emesis and no rescue medication use) in cycle 1. Sustained efficacy was evaluated during the subsequent cycles by calculating the rate of CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles. The impact of both overall CR and risk factors for CINV on the control of very late events (vomiting and moderate-tosevere nausea) were also examined.

<p>Management of Chemotherapy-Induced Nausea and Vomiting (CINV): A Short Review on the Role of Netupitant-Palonosetron (NEPA)</p>

“…35 These results were confirmed in a very recent study designed to investigate the efficacy of NEPA in breast cancer patients receiving adjuvant AC chemotherapy over multiple cycles and during the intercycle period. 36 In 149 patients on study, the proportion of patients with an overall CR was 70.5% in cycle 1, and this was maintained in subsequent cycles. Overall, the cumulative percentage of patients with a sustained CR over 4 cycles was 53%.…”

“…Indeed, in each cycle patients that reached CR experienced a significantly better control of very late nausea and/or vomiting than those who experienced no CR. 36 Moreover, another study explored the timing flexibility of NEPA administration by analyzing the occupancy of the NK 1 receptor in the brain via positron emission tomography and NEPA plasma concentration by pharmacological models. The results suggested the possibility to administer NEPA closer to initiation of chemotherapy than the recommended 60 min.…”

Exploratory analysis of the effect of a dexamethasone-sparing regimen for prophylaxis of cisplatin-induced emesis on food intake (LUNG-NEPA study)

“…The ESAS tool was translated into Italian and validated both linguistically and psychometrically 22 . The presence of a symptom was defined a priori as a score of 1 or greater, and clinically significant symptom intensity was defined as a score of 3 or greater 23 . The primary efficacy endpoint of the parent study was the proportion of patients experiencing complete response (CR; defined as no emetic episode and no use of rescue medication) in the overall study period (day 1 through 5 post-chemotherapy).…”

Netupitant-palonosetron (NEPA) for Preventing Chemotherapy-induced Nausea and Vomiting: From Clinical Trials to Daily Practice

“…Recently, two prospective, nonrandomized, single-arm studies, which were not part of the clinical development program required by regulatory agencies, assessed oral NEPA in patients with breast cancer treated with AC. The first was a phase 2 study conducted in Italy in 139 patients receiving four cycles of AC-based chemotherapy [ 48 ]. With an overall CR rate of 71% in cycle 1, oral NEPA efficacy was comparable to that in the pivotal phase 3 trial (74%) [ 40 ].…”