Authors: Akito Hata, Yoshimasa Shiraishi, Naoki Inui, Morihito Okada, Masahiro Morise, Kohei Akiyoshi, Masayuki Takeda, Yasutaka Watanabe, Shunichi Sugawara, Naofumi Shinagawa, Kaoru Kubota, Toshiaki Saeki & Tomohide Tamura
Abstract
Introduction
We describe the results of an exploratory analysis performed on the first head-to-head study (JapicCTI-194611) comparing two different intravenous (IV) neurokinin 1 (NK1) receptor antagonists, fosnetupitant and fosaprepitant, in combination with palonosetron (PALO) and dexamethasone (DEX) for the prevention of highly emetogenic chemotherapy (HEC)-induced nausea and vomiting (CINV). This analysis was performed to validate the findings of the primary analysis (previously published) utilizing a last observation carried forward (LOCF) approach for missing values for the efficacy endpoint of complete response (no emetic event and no rescue medication), while also evaluating the time periods encompassing the 0–168-hour (h) “extended overall phase” interval.
Methods
Patients scheduled to receive cisplatin-based chemotherapy were randomized 1:1 to fosnetupitant 235 mg or fosaprepitant 150 mg in combination with PALO 0.75 mg and DEX. Complete response rates were calculated and compared (stratified by age category and sex with a Mantel–Haenszel test) during the study’s primary overall phase (0–120 h) and during additional time intervals of interest [acute (0–24 h), delayed (24–120 h), extended delayed (> 24–168 h), beyond delayed (120–168 h), and extended overall (0–168 h)].
Results
A total of 785 patients were included (fosnetupitant N = 392, fosaprepitant N = 393). Complete response rates were numerically higher for fosnetupitant versus fosaprepitant for all time intervals and statistically significant for the extended overall phase. Complete response rates for fosnetupitant versus fosaprepitant during the overall, acute, delayed, extended delayed, beyond delayed, and extended overall phases were 75.5% vs. 71.0% (p = 0.1530), 93.9% vs. 92.6% (p = 0.4832), 77.0% vs. 72.8% (p = 0.1682), 74.7% vs. 68.4% (p = 0.0506), 86.7% vs. 81.7% (p = 0.0523), and 73.5% vs. 66.9% (p = 0.0450), respectively.
Conclusion
In this exploratory analysis, fosnetupitant appeared to be more effective than fosaprepitant in preventing CINV associated with cisplatin-based HEC during the extended 7-day period following chemotherapy.
Key Summary Points |
Chemotherapy-induced nausea and vomiting (CINV) is described as occurring in two arbitrarily defined phases: the acute phase (from 0 to 24 h following chemotherapy initiation) and the delayed phase (from 24 h to 120 h), with almost all antiemetic studies evaluating treatment efficacy only to 120 h after the administration of chemotherapy. |
This was the first study to compare two neurokinin 1 (NK1) receptor antagonist (RA)-containing (fosnetupitant vs. fosaprepitant) antiemetic regimens beyond the 120 h time point for prevention of cisplatin-based highly emetogenic CINV. |
The primary analysis of this study (previously published) showed non-inferiority of fosnetupitant and fosaprepitant for overall 0–120 h complete response (no emetic event and no rescue medication) rates. |
This exploratory analysis utilized a last observation carried forward (LOCF) approach for missing values for the complete response evaluation. |
Complete response rates were numerically higher for fosnetupitant than fosaprepitant during all time intervals and significantly higher for fosnetupitant in the extended overall 0–168 h phase. |
It may be prudent for clinicians to continue to assess these symptoms beyond the traditional 5-day period after cisplatin-based chemotherapy. |