Aim

To assess the efficacy of oral NEPA (netupitant-palonosetron 300/0.50 mg) over multiple chemotherapy cycles.

Methods

Two randomized phase III studies evaluated a single dose of oral NEPA given on day 1 in chemotherapy-naive patients receiving anthracycline-cyclophosphamide (AC)-based (Study 1) or highly (HEC)/moderately (MEC) emetogenic chemotherapy (safety Study 2). Oral NEPA was compared with oral palonosetron 0.50 mg (Study 1) or oral aprepitant 125 mg day 1, 80 mg days 2-3/palonosetron 0.50 mg (Study 2; no formal statistical comparisons). Oral dexamethasone was administered in all treatment groups. Complete response (CR; no emesis/no rescue medication), no emesis, and no significant nausea (NSN) rates during acute (0-24 h) and delayed (>24-120 h) phases of chemotherapy cycles 1-4 in each study were evaluated.

Results

In Study 1, 1450 patients received 5969 chemotherapy cycles; in Study 2, 412 patients received 1961 chemotherapy cycles. In each study, ≥75% of patients completed 4 or more cycles. In Study 1, oral NEPA was superior to palonosetron in preventing chemotherapy-induced nausea and vomiting (CINV) in the acute and delayed phases of cycle 1, with higher rates of CR (all P < 0.05), no emesis (all P < 0.05), and NSN (delayed phase P < 0.05 cycles 1, 2, and 4) reported across 4 cycles. In Study 2, oral NEPA had numerically higher CR and NSN rates in the acute and delayed phases than aprepitant-palonosetron in MEC/HEC patients.

Conclusion

Oral NEPA was highly effective in preventing both acute and delayed CINV over multiple chemotherapy cycles of HEC, AC, and MEC regimens.

Clinical trial registration numbers

Study 1, NCT01339260; Study 2, NCT01376297.

Purpose

Our goal was to identify new anticancer agents approved by the US Food and Drug Administration (FDA) and the European Medical Agency (EMA) since the 2016 MASCC/ESMO antiemetic update and classify their emetic potential.

Methods

The MASCC/ESMO Expert Panel classified the emetogenicity of the identified new antineoplastic agents based on nonsystematic reviews of randomized controlled trials, analysis of product labeling, and evaluation of emetic classification in other international guidelines and informal consensus. The emetogenic classification system for oral anticancer agents was revised into two emetic risk categories (minimal-low; moderate-high) to be consistent with the system reported by ASCO (American Society of Clinical Oncology) in their 2017 guideline update. The previously employed four emetic risk classification categories for intravenously administered antineoplastic agents were retained for this update.

Results

From June 2015 to January 2023, 107 new antineoplastic agents (44 intravenously administered and 63 orally administered agents) were identified. The reported incidence of vomiting varied significantly across studies for many agents, especially for oral anticancer agents.

Conclusion

The MASCC/ESMO Expert Panel acknowledges the limitations of our efforts to classify the emetic potential of anticancer agents, especially the imprecision associated with oral agents. However, we have attempted to provide a reasonable approximation of the emetic risk associated with new antineoplastic agents by searching the available literature and reviewing other available international antiemetic guidelines.