NEPA is an oral single, fixed-dose combination of netupitant, a new highly selective NK 1 RA and palonosetron (PALO), a pharmacologically/clinically distinct 5-HT 3 RA. It delivers antiemetic guideline-recommended prophylaxis by targeting two critical molecular pathways associated with chemotherapy-induced nausea/vomiting. This Phase III study demonstrated the superiority of NEPA compared with PALO.

Intravenous NEPA was well-tolerated with a similar safety profile to oral NEPA in patients with various solid tumors receiving HEC.

BackgroundNeutropenic patients are at risk of abdominal complications and yet the incidence and impact of these complications on patients' morbidity and mortality have not been sufficiently evaluated. We aimed to assess a clinical rule for early detection of abdominal complications leading to death or transfer to intensive care in patients with chemotherapy-associated neutropenia. Design and MethodsThis observational multicenter study was carried out in seven German hematology-oncology departments. For inclusion, neutropenia of at least 5 consecutive days was required. Risk factors for "transfer to intensive care" and "death" were assessed by backward-stepwise binary logistic regression analyses. Chemotherapy-associated bowel syndrome was defined as a combination of fever (T ≥37.8 °C) and abdominal pain and/or lack of bowel movement for 72 hours or more. Five hundred and twenty-one neutropenic episodes were documented in 359 patients. ResultsThe incidence of chemotherapy-associated bowel syndrome was 126/359 (35%) in first episodes of neutropenia. Transfer to intensive care occurred in 41/359 (11%) and death occurred in 17/359 (5%) first episodes. Chemotherapy-associated bowel syndrome and duration of neutropenia were identified as risk factors for transfer to intensive care (P<0.001; OR 4.753; 95% CI 2.297-9.833, and P=0.003; OR 1.061/d; 95% CI 1.021-1.103). Chemotherapyassociated bowel syndrome and mitoxantrone administration were identified as risk factors for death (P=0.005; OR 4.611; 95% CI 1.573-13.515 and P=0.026; OR 3.628; 95% CI 1.169-11.256). ConclusionsThe occurrence of chemotherapy-associated bowel syndrome has a significant impact on patients' outcome. In future interventional clinical trials, this definition might be used as a selection criterion for early treatment of patients at risk of severe complications.Key words: neutropenia, chemotherapy-associated bowel syndrome, risk prediction.Citation: Vehreschild MJGT, Meißner AMK, Cornely OA, Maschmeyer G, Neumann S, von Lilienfeld-Toal M, Karthaus M, Wattad M, Staib P, Hellmich M, Christ H, and Vehreschild J-J. Clinically defined chemotherapy-associated bowel syndrome predicts severe complications and death in cancer patients.

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Background The oral fixed dose combination of netupitant and palonosetron NEPA has been approved for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in cancer patients receiving cisplatin-based highly emetogenic (HEC) or moderately emetogenic chemotherapy (MEC). The primary objective of the prospective, non-interventional study (NIS) AkyPRO is the evaluation of quality of life in adults receiving MEC or HEC and NEPA for CINV prevention. Secondary endpoints are efficacy and safety of NEPA. Here we present an interim analysis of NEPA efficacy in the subgroup of breast cancer patients, who represent the largest subgroup (66%) of enrolled patients. Since September 2015, 2427 patients have been enrolled, of whom 986 are breast cancer patients. Methods The NIS has been designed to evaluate NEPA in 2,500 cancer patients receiving single day or two day MEC or HEC. QoL is recorded by FLIE questionnaires. Efficacy (complete response (CR, no vomiting, no rescue medication)), additional medication, and adverse events are recorded in patient diaries over three consecutive chemotherapy cycles. Additionally, physicians report their efficacy assessments of NEPA online, using an eCRF. Results At the cut-off date November 11, 2017, 2427 patients had been enrolled in the study. For the interim analysis 986 breast cancer patients were evaluated who had been fully documented in the eCRF at the cut-off date. 95% had an ECOG performance status of 0 or 1. 51% received adjuvant, 44% neoadjuvant, and 5% palliative chemotherapy. 80% of patients received HEC, mostly (79%) anthracycline/cyclophosphamide (AC) combinations. Of the women receiving MEC, the majority were treated with carboplatin-based regimens (9%). 7% of patients received other MEC regimens. 81.4-82.8 % of patients reported CR in cycles 1-3 and more than 93% of patients reported no emesis during the 3 treatment cycles covered in the patient diaries. No significant nausea was reported by 62.7-64.2% of patients. Physicians rated the efficacy of the antiemetic prophylaxis with NEPA using the 4 categories very good, good, satisfactory, and poor. In cycles 1 and 2, more than 89% of physicians rated the efficacy of NEPA very good or good. In cycle 3, 90.6% rated it very good or good. In addition to reporting CR, nausea and emesis episodes in their patient diaries, patients used the same 4 categories to assess the efficacy of NEPA at the end of each treatment cycle. Efficacy assessments of physicians and patients were very similar, with 87% of patients choosing very good or good in cycle 1 compared to 89% of physicians. NEPA was well tolerated. Low-grade constipation (14.9%) and insomnia (8.3%) were the most frequent treatment-related adverse event. Conclusion In this real life study, NEPA was effective in the prevention of CINV in the subgroup of breast cancer patients receiving HEC or MEC. The efficacy assessments by patients and physicians were comparable, with approximately 90% good or very good efficacy for 3 consecutive cycles. More than 93% of patients reported no emesis and more than 81% reported CR during the 5 days post-chemotherapy during all 3 cycles. The study is ongoing. Citation Format: Schilling J, Hielscher C, Hanusch C, Kurbacher C, Busch S, Karthaus M. Efficacy of NEPA as antiemetic prophylaxis in breast cancer patients receiving highly or moderately emetogenic chemotherapy – Interim results of a German prospective, non-interventional study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-10.