The impact of NK1 receptor antagonist selection on chemotherapy-related adverse events: a retrospective study of adverse events in paclitaxel or nab-paclitaxel and carboplatin combination therapy with fosnetupitant and aprepitant use

Netupitant (NTP), the active form of fosnetupitant (FosNTP), a novel NK1 receptor antagonist, has been reported to possess a longer half-life than conventional drugs and demonstrates favorable antiemetic effects in the delayed phase. However, NTP has been reported to exert an inhibitory effect on CYP3A4, similar to conventional NK1 receptor antagonists. Paclitaxel (PTX), which is utilized in the treatment of non-small cell lung cancer, undergoes metabolism via CYP3A4. The enhancement of myelosuppression resulting from this interaction may necessitate dose reduction or withdrawal of anticancer drugs, which may compromise treatment continuation. While it has been reported that aprepitant (APR) does not influence the incidence of adverse events associated with anticancer drugs metabolized via CYP3A4, reports on FosNTP remain limited. Therefore, this study retrospectively examined the differences in the incidence of myelosuppression as an adverse event in patients with non-small cell lung cancer treated with FosNTP and APR. Patients treated with PTX or nanoparticle albumin-bound paclitaxel (nab-PTX) combined with platinum-based anticancer regimens for non-small cell lung cancer between January 2019 and September 2024 were included in this study. Patients receiving FosNTP and APR as antiemetic agents were stratified into groups, and the incidence of grade ≥3 myelosuppression served as the primary endpoint. Statistical analysis was performed using the chi-square test, with statistical significance established at P < 0.05. The incidence of grade ≥3 neutropenia was 15/31 in the FosNTP group and 18/68 in the APR group among PTX-treated patients, demonstrating a significantly higher incidence in the FosNTP group (48.4% vs. 26.5%; p = 0.019). The extended half-life of NTP compared to that of APR may have contributed to prolonged CYP3A4 inhibition and subsequent inhibition of PTX metabolism. Conversely, among nab-PTX users, 10/49 patients in the FosNTP group and 8/53 patients in the APR group developed grade ≥3 neutropenia, with no significant difference observed (20.4% vs. 17.0%; p = 0.182). This study suggests that the use of FosNTP in PTX-containing regimens may lead to a higher incidence of grade ≥3 neutropenia compared to APR, emphasizing the importance of vigilant monitoring throughout the treatment period.