Assessing duration of breakthrough chemotherapy-induced nausea and vomiting (CINV): A pooled study analysis of NEPA versus aprepitant.

12091 Background: The historical standard clinical trial endpoint for preventing chemotherapy-induced nausea and vomiting (CINV) has been assessment of complete response (CR: no emesis and no rescue medication use) over five days. Recent evaluations focused on the duration of breakthrough CINV suggest that long duration of CINV results in more lost work time and impaired activity and is also a strong predictor for CINV in subsequent cycles. A recent pooled analysis of three similarly designed registration trials of NEPA, a fixed oral combination NK1 receptor antagonist (RA) (netupitant)/5-HT3RA (palonosetron), showed significantly higher CR rates during the delayed phase (≥24-120h) for NEPA compared to an aprepitant (APR) regimen. In this post-hoc analysis, we evaluated the extent and duration of breakthrough CINV in these pooled studies. Methods: Chemotherapy-naïve patients who received cisplatin-based chemotherapy and antiemetic prophylaxis of either a single dose of NEPA plus dexamethasone (DEX) or a 3-day APR/5-HT3 RA/DEX regimen from three randomized, double-blind pivotal trials were included. Patients without a CR were defined as treatment failures. Extent of CINV was evaluated using proportions of patients with treatment failure, emesis, and significant nausea (defined as >25 mm on a 100 mm visual analog scale). Over the 5-day overall phase, duration was categorized as 1-2, and ≥3 days. Pearson’s chi-square test was employed to compare risks between treatments for each duration category in each of the previously mentioned endpoints. Results: Among all 621 NEPA and 576 APR patients, a significantly greater proportion of APR patients experienced treatment failure, emesis, and significant nausea for ≥3 days. Specifically, among patients with treatment failure, 31% (41/134) who received NEPA and 43% (61/143) who received APR experienced breakthrough CINV for ≥3 days. Conclusions: Expanding on data suggesting single-day NEPA is more effective than 3-day APR in preventing delayed CINV, NEPA is also more effective in minimizing the extent and duration of CINV in patients with breakthrough emesis and nausea.[Table: see text]

Noninferiority study evaluating dexamethasone (DEX)-sparing regimens administered with NEPA, a fixed combination of netupitant and palonosetron, for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by high-dose cisplatin.

12093 Background: Corticosteroids such as DEX continue to play a key role for the prevention of CINV. Although they are generally considered safe when used in combination with other anti-emetic agents, corticosteroids can cause a range of side effects. To reduce the overall exposure to DEX in patients receiving cisplatin-based chemotherapy, we evaluated the non-inferiority of DEX on day 1, with or without low-dose DEX on days 2 and 3, combined with oral NEPA, a fixed combination of the NK1 receptor antagonist (RA), netupitant and 5-HT3 RA, palonosetron, compared with NEPA plus the guideline-recommended use of 4-day DEX (reference arm). Non-inferiority was met for both DEX-sparing regimens and the reference arm for the primary endpoint of complete response (CR: no emesis and no rescue use) during the overall (0-120h) phase post-chemotherapy. In this analysis secondary efficacy endpoints were evaluated for the single-dose DEX-sparing group versus the 4-day DEX arm. Methods: In this analysis from an open-label, multicenter study (ClinicalTrials.gov NCT04201769) chemotherapy-naïve patients undergoing high-dose cisplatin (≥70 mg/m2) received either NEPA and DEX (12 mg) on day 1 only or NEPA and DEX [12 mg on day 1 plus 4 mg twice daily on days 2-4 (DEX4)]. Efficacy endpoints included complete protection (CR plus no significant nausea), no emesis, and no significant nausea (<25 mm on a 100 mm visual analog scale) during the acute (0-24h), delayed (>24-120h) and overall phases. The non-inferiority margin was set at -15% difference (DEX1 minus DEX4). Results: One-hundred fifty-two patients, 76 in each arm, were included. Non-inferiority was met for the DEX1 arm and the DEX4 reference arm for all efficacy endpoints (Table). Conclusions: A simplified regimen of NEPA plus single-dose DEX offers comparable CINV prevention throughout 5 days post-chemotherapy with the advantage of sparing patients additional doses of DEX in the high emetic risk setting of cisplatin-based chemotherapy. Clinical trial information: NCT04201769. [Table: see text]

Single-dose netupitant/palonosetron versus 3-day aprepitant for preventing chemotherapy-induced nausea and vomiting: a pooled analysis

Aim: In the absence of comparative studies, guidelines consider neurokinin 1 receptor antagonists (RAs) as interchangeable. We evaluated the pooled efficacy from three cisplatin registration trials, each with arms containing netupitant/palonosetron (NEPA), a fixed neurokinin 1 RA (netupitant)/serotonin Type 3 (5-HT3) RA (palonosetron) combination, and an aprepitant (APR) regimen. Materials & methods: Efficacy data were pooled for rates of complete response (CR: no emesis/no rescue medication), complete protection (CR + no significant nausea), total control (CR + no nausea) and no significant nausea during acute (0–24 h), delayed (>24–120 h) and overall (0–120 h) phases post chemotherapy. Results: Among 621 NEPA and 576 APR patients, response rates were similar for the acute phase, and generally favored NEPA during delayed and overall phases. CR rates for NEPA versus APR were 88.4 versus 89.2%, 81.8 versus 76.9% (p < 0.05) and 78.4 versus 75.0% during the acute, delayed and overall phases, respectively. Conclusion: Oral NEPA administered on day 1 was more effective than a 3-day APR regimen in preventing delayed nausea and vomiting associated with cisplatin.

Osmangazi University score to reduce ionizing radiation in renal colic patients in emergency department

Objective: Computerized tomography remains the gold standard imaging in renal colic patients. In this study, we develop a scoring system to select patients in emergency department for unnecessary computerized tomography imaging in order to decrease radiation exposure. Methods: Computerized tomography imaging of patients with renal colic in emergency department were retrospectively reviewed. Symptoms, laboratory results were recorded. Significant parameters were determined by univariate and multivariate analysis. Coefficients were found to obtain score points and receiver operating curve was used to find a cut-off value. Results: A total of 123 patients with a mean age of 42 years (18–75 years) were enrolled in the study. About, 20.3% of patients were stone-free in computerized tomography. Mean stone size was 6.1 ± 1.89 mm. According to analysis, four parameters were significant; nausea, stone history, creatinine, and hematuria with a total score 9 called as Osmangazi University STONE score. Cut-off value was found as >3, which computerized tomography imaging is recommended. Conclusion: Osmangazi University STONE score is useful and simple tool in emergency department to reduce unnecessary computerized tomography imaging in renal colic patients and also lowers cost and ionizing radiation exposure.

The risk factors for vomiting and nausea in patients with oxaliplatin-based chemotherapy: Subgroup analysis of SENRI trial.

779 Background: We previously reported, in the SENRI trial, usefulness of aprepitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in colorectal cancer patients receiving an oxaliplatin-based regimen which is classified as moderately emetogenic cancer chemotherapy. In this study, we assessed the risk factors for CINV in colorectal cancer patients who received Oxaliplatin-based chemotherapy. Methods: A total of 370 patients was analyzed as for the rate of vomiting, and significant nausea in overall phase. We also assessed the proportion of CINV in patients divided by gender. Results: First, we analyzed the risk factors for vomiting and nausea. Female gender and aprepitant use were associated with the incidence of vomiting and significant nausea. Significantly more women suffered from vomiting than men (84.5 % vs. 92.9 % in women and men, respectively; P= 0.0001). The rate of no nausea, complete response, complete protection, and total control was also lower in women. The rate of use of rescue therapy was significantly higher in women. We compared the rate of CINV between aprepitant and control groups and found that, in women, the rate of no nausea, no vomiting, and total control was higher in the aprepitant group than in the control group. Conclusions: Gender and no aprepitant use were risk factors of CINV in colorectal patients who received oxaliplatin-based chemotherapy.Aprepitant therapy was more effective for women than for men in the prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen. Clinical trial information: NCT01344304.

Rolapitant for the prevention of nausea in patients receiving moderately or highly emetogenic chemotherapy.

224 Background: Nausea control remains an unmet need for patients receiving moderately or highly emetogenic chemotherapy (MEC, HEC). The objective of this analysis was to determine the effect of the neurokinin-1 (NK-1) receptor antagonist rolapitant (VARUBI) on the prevention of nausea in patients receiving either MEC or HEC. Methods: Post hoc analyses of nausea from three randomized, double-blind, active-controlled, phase 3 clinical trials were performed for carboplatin-based MEC (n = 401), non-carboplatin-based MEC (n = 228), total MEC (n = 629), anthracycline/cyclophosphamide (AC)-based chemotherapy (n = 703), and cisplatin-based HEC (n = 1070). Patients were randomized 1:1 to oral rolapitant 180 mg or placebo ~1–2 h before chemotherapy. All patients received active control: granisetron 2 mg oral or 10 mcg/kg IV and oral dexamethasone 20 mg. Granisetron was continued on days 2 and 3 for patients receiving MEC or AC-based therapy and dexamethasone 8 mg twice daily on days 2–4 for patients receiving HEC. Patients self-assessed nausea on days 1–6 using a 100-mm visual analog scale (VAS). Percentage of patients with no nausea (NN; maximum VAS < 5 mm) or no significant nausea (NSN; maximum VAS < 25 mm) was determined for overall, delayed, and acute phases of CINV in cycle 1. Results: Rates of NN in the carboplatin-based MEC and total MEC subgroups were significantly higher (P < 0.05) with rolapitant than active control in the delayed and overall phases. In the cisplatin-based HEC subgroup, rates of NN and NSN were significantly higher (P < 0.05) with rolapitant than active control in the delayed, acute, and overall phases. Conclusions: Rolapitant prevents nausea during all CINV phases in patients receiving cisplatin-based HEC, and during the delayed and overall phases in patients receiving carboplatin-based MEC. Clinical trial information: NCT01500226, NCT01499849, NCT01500213.

Efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with gastrointestinal and colorectal cancers.

222 Background: Rolapitant (VARUBI) is a selective, long-acting neurokinin-1 receptor antagonist (RA) for the prevention of CINV. Rolapitant effectively prevented CINV in phase 3 trials of patients (pts) receiving highly or moderately emetogenic chemotherapy (HEC, MEC). While MEC and HEC regimens are commonly used to treat pts with gastrointestinal and colorectal cancers (GI/CRC), very few studies have evaluated the effectiveness of a neurokinin-1 RA regimen in these pts. We assessed the incidence of CINV and efficacy of rolapitant in a subset of pts with GI/CRC. Methods: This is a post hoc analysis of 3 similarly-designed, randomized, placebo-controlled trials. Pts with cancer of the esophagus, stomach, colon/rectum, or anus received a single oral dose of 180 mg oral rolapitant or placebo prior to HEC or MEC. All pts received a 5-hydroxytryptamine type 3 (5-HT3) RA and dexamethasone (active control). The HEC studies included cisplatin, and the MEC study carboplatin, oxaliplatin, irinotecan, epirubicin, and doxorubicin. Endpoints included complete response (CR; no emesis and no use of rescue medication), no emesis, no nausea (maximum visual analogue scale [VAS] < 5 mm), no significant nausea (maximum VAS < 25mm) and complete protection (CP; no emesis, no use of rescue medication, and no significant nausea) in the overall (0-120 h), acute (≤ 24 h), and delayed (> 24-120 h) phases. Results: Out of 188 GI/CRC pts, 101 pts received rolapitant and 87 received active control. Pts treated with rolapitant had significantly higher rates of CR, no nausea, no emesis, and CP in the overall phase (P < 0.05). Rolapitant was well-tolerated and overall incidence of treatment-emergent adverse events comparable in both groups. Conclusions: Addition of rolapitant to 5-HT3RA and dexamethasone therapy significantly improved CR, no nausea, no emesis, and CP in pts with GI/CRC receiving emetogenic chemotherapy. Clinical trial information: NCT01500226, NCT01499849, NCT01500213. [Table: see text]

Netupitant/palonosetron (NEPA) for prevention of delayed chemotherapy-induced nausea and vomiting (CINV) in multiple cycles of chemotherapy.

211 Background: Prevention of CINV in the delayed phase (24-120 h post-chemotherapy) and over multiple cycles of chemotherapy remains a challenge. NEPA, a fixed combination of the NK1 receptor antagonist (RA) netupitant (300 mg) and the 5-HT3 RA palonosetron (PALO; 0.5 mg), has demonstrated efficacy in multiple studies, in both acute and delayed phases, during the first cycle of moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) regimens. Two clinical trials evaluated NEPA over multiple cycles of chemotherapy. We report data for the delayed phase for each cycle. Methods: Both studies were Phase 3, double-blind, active-controlled studies. In study 1 (MEC), patients were randomized 1:1 to receive a single oral dose of NEPA (n = 724) or PALO 0.5 mg (n = 725) on Day 1; following cycle 1, patients could participate in a multi-cycle extension phase. In study 2 (MEC or HEC), patients were randomized 3:1 to receive a single oral dose of NEPA on Day 1 (n = 309) or oral aprepitant (APR) 125 mg plus oral PALO 0.5 mg on Day 1, then APR 80 mg/d on days 2 and 3 of each cycle (n = 103). In both studies, all patients also received dexamethasone. Efficacy endpoints included complete response (CR; no emesis, no rescue medication) and no significant nausea. Results: In both studies, CR rates were consistently numerically higher with NEPA (Study 1 range: 77%-89%; Study 2 range: 83%-93%) than with PALO (Study 1; range: 69%-83%) or APR/PALO (Study 2; range: 78%-88%) in each cycle up to cycle 6 (Table). In both studies, rates of no significant nausea in the NEPA group were similar to or higher than in the control group. NEPA was well tolerated in both studies; treatment-related adverse events included constipation and headache. Conclusions: These studies demonstrate sustained efficacy of NEPA (administered as a single dose on Day 1) across multiple cycles of MEC or HEC for prevention of CINV in the delayed phase. Clinical trial information: 2009-016775-30; 2010-023297-39. [Table: see text]

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients (pts) receiving anthracycline-cyclophosphamide (AC)-based chemotherapy.

208 Background: Rolapitant, a novel NK-1 receptor antagonist, demonstrated efficacy in the prevention of CINV in pts receiving moderately- or highly emetogenic chemotherapy (MEC; HEC). In this post-hoc analysis, we evaluated safety and efficacy outcomes in pts receiving AC-based therapy, now considered HEC. Methods: This double-blind, active-controlled study randomized pts to oral rolapitant 180 mg plus granisetron 2 mg and dexamethasone 20 mg or granisetron/dexamethasone alone (active control). Complete response (CR = no emesis and no use of rescue medication), no emesis, no significant nausea, and time to emesis or rescue medication during overall, acute, and delayed phases and treatment-emergent adverse events (AEs) are presented. Results: 703 pts received AC-based therapy, of which 97% had breast cancer. CR was significantly higher for rolapitant vs. active control for delayed and overall phases in pts receiving AC-based therapy (Table). Time to first emesis or use of rescue medication was significantly longer with rolapitant vs. active control (between-group comparison, p = 0.032); median was not reached in either treatment arm. A significantly greater proportion of pts on rolapitant (73.0%) vs. active control (60.2%) had no emesis during the overall phase (p < 0.001). Rates of no significant nausea were similar for rolapitant (63.7%) and active control (62.4%) in the overall phase (p = 0.728). Treatment-related AEs (TRAEs) during Cycle 1 occurred in 8.7% and 8.8% of pts on rolapitant vs. active control. Most frequent TRAEs were constipation (2.9% vs. 2.7%), fatigue (2.3% vs. 2.2%), and headache (2.3% vs. 3.3%). Conclusions: Rolapitant was superior to active control in preventing CINV during delayed and overall phases after AC-based chemotherapy. The safety profiles of the rolapitant and control arms were similar. These results are consistent with those of the overall pt population in this study. Clinical trial information: NCT01500226. [Table: see text]

Evaluation of nausea control with NEPA, a novel oral combination antiemetic.

169 Background: The introduction of NK1 receptor antagonists (RAs) improved the control of chemotherapy-induced nausea and vomiting. However, prevention of nausea, particularly in the delayed phase remains suboptimal, with no consistent superiority seen with the addition of aprepitant over 5-HT3 RAs + dexamethasone (DEX). NEPA, a fixed-dose oral combination of the new NK1RA, netupitant (NETU 300 mg) plus palonosetron (PALO 0.50 mg) targets two main antiemetic pathways with a convenient single dose. NEPA has shown superior complete response rates (no vomiting and no rescue use) compared with PALO in pivotal trials. This analysis summarizes the nausea control seen with NEPA in all 3 pivotal trials in the clinical development program. Methods: Patients in 3 randomized, double-blind trials received a single dose of NEPA + DEX prior to a variety of either highly emetogenic (HEC) (Studies 1 and 3) or moderately emetogenic (MEC) (Studies 2 and 3) chemotherapeutic agents. Patients receiving HEC also received additional DEX on Days 2–4. Nausea was measured daily with a 100 mm visual analog scale (VAS). The proportion of patients with no significant nausea (VAS <25 mm) were summarized (Table). Results: In Studies 1 and 2, NEPA was significantly more effective in controlling delayed and overall nausea compared with PALO (Table). The greatest nausea control with NEPA was seen in the non-AC MEC and HEC settings. Conclusions: This summary suggests that NEPA + DEX improves control of nausea during the delayed and overall periods following chemotherapy. High levels of nausea control were seen and were most noteworthy in patients receiving HEC or non-AC MEC. Clinical trial information: NCT01339260; NCT01376297. [Table: see text]