MEC Regimens Research Articles

An Indian real-world experience of intravenous fosnetupitant-palonosetron (IV NEPA) in preventing delayed and extended delayed CINV.

12070 Background: Although the reports suggest 15-25% cancer patients receiving highly- and moderately emetogenic chemotherapy (HEC and MEC) experience nausea and vomiting beyond day 5, majority of clinical trials focus on delayed chemotherapy induced nausea and vomiting (CINV) only during the first 5 days of treatment. Here we present a real world observational data with fixed combination of IntraVenous (Fos)NEtupitant and Palonosetron (IV NEPA) in preventing nausea/vomiting in delayed and extended delayed phase among patients receiving HEC/MEC. Methods: An open label, single arm, multicentre, phase IV prospective trial was conducted at six centres following individual Institutional Ethics Committee approval (CTRI/2023/04/051951). Patients in acute (0-24hrs), delayed (>24-120hrs), extended delayed (>120-240hrs) phases and extended overall phase (0-240hrs) were assessed for complete response (CR) (no vomiting and no need of rescue medication), complete protection (CP) [CR + no significant nausea (5mm to <25mm) on visual analogue scale], complete control (CC) [CR + no nausea (<5mm)] and safety. Results: Among 178 patients (Males-114, Females-64), 90 (50.56%) received HEC and 88 (49.44%) received MEC regimen. Cisplatin-Paclitaxel (19.10%) and Carboplatin-Paclitaxel (35.39%) were the most common HEC and MEC regimens respectively. Overall, CR in delayed and extended delayed phases were 93.26% and 96.07% respectively. Furthermore, CP and CC in delayed and extended delayed phases were 92.13% and 96.07% and 81.46% and 90.45% respectively (Table). In general, IV NEPA was well tolerated, as only 9.55% of patients experienced adverse events with 95.83% of them being mild in nature. Headache (2.25%) and injection site reactions (1.68%) were the most common adverse effect reported. Conclusions: IV NEPA demonstrated high efficacy and good tolerability in a real world Indian setting, exhibiting response rates of >92% in both delayed and extended delayed phases in patients receiving HEC/MEC regimens. Clinical trial information: CTRI/2023/04/051951. [Table: see text]

An Open-Label, Single-Arm, Multicenter, Observational Study Evaluating the Safety and Effectiveness of Akynzeo® in the Management of Chemotherapy-Induced Nausea and Vomiting in India.

Background Chemotherapy-induced nausea and vomiting is a common and unpleasant treatment-related side effect reported by cancer patients receiving chemotherapy. Akynzeo® or NEPA (NEtupitant + PAlonosetron) is the first fixed combination of netupitant and palonosetron that targets both critical pathways involved in emesis while providing a convenient, single oral dose therapy. The current study aimed to assess the effectiveness and safety of NEPA in a real-world setting in India. Methodology This was an open-label, multicenter, prospective, single-arm study conducted at six different locations across India. The study included patients of either gender, aged ≥18 years, naive to chemotherapy, scheduled to receive highly or moderately emetogenic chemotherapy (HEC/MEC), and scheduled to receive oral NEPA, as determined by the investigator. Results A total of 360 people were screened and enrolled in the study. HEC was prescribed to 289 (81.64%) patients, while MEC was prescribed to 65 (18.36%) patients. Complete response was achieved in 94.92% of patients during the acute phase, 95.20% during the delayed phase, and 93.22% during the overall phase. During the overall phase, 92.73% and 95.38% of patients on the HEC and MEC regimens, respectively, achieved complete response. Adverse events were reported in 3.88% of patients. Conclusions Oral NEPA was found to be effective in the Indian real-world setting, eliciting a >90% complete response with HEC and MEC regimens across the acute, delayed, and overall phases.

Evaluation of Current Antiemetic Therapy Response in Patients Undergoing MEC or HEC Regimens in Portugal.

Chemotherapy-induced nausea and vomiting (CINV) negatively impact cancer patients' quality of life and treatment outcomes. This study evaluated the achievement of complete response to CINV prophylaxis during the first five days after chemotherapy in adult outpatient cancer clinics with solid malignant tumours receiving Moderate or Highly Emetogenic Chemotherapy (MEC or HEC) in Portugal. During the study, patients completed three evaluations, and nausea severity and CINV impact on patients' daily life was assessed. A complete response (no emetic episodes, no use of rescue antiemetic medication, and no more than mild nausea) was observed in 72% of the cycles (N = 161) throughout the five days after chemotherapy. Amongst the patient population, 25% classified their CINV episodes as severe. Though more than half of the patients achieved a complete response, suggesting that a therapeutic effort is being made to minimise this side effect, the overall scenario is barely optimistic. Significantly, new CINV-control measures in MEC/HEC patients should be adopted, specifically avoiding the single use of dexamethasone and 5-HT3 and raising awareness of using NK1-RAs. Thus, it is critical to improve CINV prophylactic treatment and implement practical international antiemetic guidelines in Portuguese clinical practice, envisaging the improvement of supportive care for cancer patients.

Real-world multicenter study of the safety and efficacy of netupitant plus palonosetron fixed-dose combination to prevent chemotherapy-induced nausea and vomiting among Malaysian patients receiving moderately or highly emetogenic chemotherapy.

A large proportion of cancer patients are at high risk for chemotherapy-induced nausea and vomiting (CINV), but the choice of anti-emetics for CINV in Malaysia is limited. This was a real-world study of a fixed-dose combination of netupitant and palonosetron (NEPA) to inhibit CINV in adult patients receiving moderately (MEC) or highly emetogenic chemotherapy (HEC) for solid/hematological malignancies at eight Malaysian centers. Each HEC/MEC cycle received one dose of NEPA + dexamethasone for CINV prevention. Complete response (no emesis, no rescue medication) (CR), no more than mild nausea (severity score≤2.5), and complete control (CR) (no more than mild nausea) during the acute (0-24h), delayed (25-120h), and overall (0-120h) phases post-chemotherapy were measured. Treatment-related adverse events (AEs) were recorded. During March 2016-April 2018 (NMRR-17-3286-38282), NEPA + dexamethasone was administered to 54 patients (77.8% solid, 22.2% hematological malignancies). Note that 59.3% received HEC, while 40.7% received MEC regimen. During the overall phase of the first cycle, the majority had CR (77.8%), no more than mild nausea (74.1%), and complete control (61.1%). Seventeen patients received two consecutive cycles at any point of chemotherapy cycles. During the overall phases across two consecutive cycles, all patients achieved CR, and the majority reported no more than mild nausea and complete control. No grades 3-4 AEs were reported. NEPA had sustained efficacy and tolerability at first administration and across two cycles of MEC/HEC for CINV prevention.

Superior Survival Outcome of Blinatumomab Compared to Mitoxantrone-Etoposide-Cytarabine Salvage for Adult Patients with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: A Propensity Score-Matched Cohort Analysis

Background: Complete remission (CR) rate and long-term overall survival (OS) is very poor in patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). Previous clinical trials revealed a good remission rate and a safe bridging role to allogeneic-HCT compared to various standard treatments, and several real-world data have been reported.Aim: Here, we analyzed outcome of blinatumomab versus our conventional intensive chemotherapy by propensity score-matched analysis.Methods: From 2009 to 2020, 197 consecutive R/R BCP-ALL were treated with mitoxantrone-etoposide-cytarabine (MEC, n=113) or blinatumomab (n=84), and allogeneic-HCT was planned in patients with CR. For propensity score-matching, the MEC and blinatumomab cohorts were matched in a 1:1 ratio using 5 criteria of age < 35 years old, short CR duration < 12 months, adverse-risk karyotype including Ph-chromosome at relapse, previous allogeneic-HCT, and first-line salvage or not. We compared CR rate, regiment related mortality, and OS with cumulative incidence of relapse (CIR) and non-relapse mortality (NRM).Results: Matched cohort consisted of 52 patients for each salvage group and matched criteria were the same exactly. Median age was 42 years and 34 (65.4%) patients were > 35 years old. There were 22 (42.3%) primary refractoriness, 9 (17.3%) post-chemotherapy relapse and 21 (40.4%) post-HCT relapse. Among 30 relapsed patients, 19 (63.3%) were early relapse with CR duration less than 12 months. There were 25 (48.1%) with poor-risk karyotype at relapse of which 10 were Philadelphia-chromosome. Extramedullary relapse was observed in 14 (26.9%) and 8 (15.4%) were advanced-line salvage. CR rate was significantly higher in blinatumomab (78.8% vs. 53.8%, p=0.012) and more patients proceeded to allo-HCT (80.8% vs. 46.2%, p<0.001). Regimen-related mortality was significantly higher in MEC (40.4% vs. 1.9%, p<0.001). After median follow-up of 32.5 months (range 6.2 to 131.2), 3-year OS of blinatumomab and MEC was 33.2% and 15.4% (p<0.001), and 3-year NRM was 30.3% and 51.9% (p=0.004), respectively. After CR achievement, CIR was not significantly different (46.9% vs. 60.0%). In multivariate analysis, CR duration < 12 months was related with poor OS with high CIR. MEC regimen showed poor OS with high NRM. High NRM was also related with advanced-line salvage.Conclusion: Our matched cohort analysis clearly showed that blinatumomab is superior to MEC salvage regimen. However, we are observing relapse in up to 50% after blinatumomab and following allo-HCT still shows high NRM. Further combinatorial using novel therapeutics are needed for R/R BCP-ALL. [Display omitted] DisclosuresKim: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AIMS Biosciense: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AML-Hub: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL & H: Research Funding; BMS & Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boryung Pharm Co.: Consultancy; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Consultancy, Honoraria; LG Chem: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Pintherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Speakers Bureau; SL VaxiGen: Consultancy, Honoraria; VigenCell: Consultancy, Honoraria. Lee: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Outcomes and Prognostic Scoring System for Elderly Patients with Acute Myeloid Leukemia

Background: The prognosis of elderly patients with acute myeloid leukemia (AML) remains poor. Elderly patients are frequently intolerant to intensive chemotherapy due to poor performance status and co-morbidities. Moreover, considering the increase of genetic abnormalities, it is disputable whether conventional chemotherapy improves the prognosis of elderly AML patients. The purpose of this study is to identity patients who would benefit from conventional chemotherapy. Patients and Methods: We retrospectively analyzed the outcome of patients with AML aged over 65 years who received conventional chemotherapy based on the JALSG GML 200 protocol at our institution between December 2011 and January 2020. Patients with acute promyelocytic leukemia were excluded. No patients underwent hematopoietic cell transplantation (HCT). Dose reduction of each regimen was considered in patients over 70 years of age. MEC regimen was used for reinduction therapy in 70% of patients with induction failure. The primary end point was overall survival (OS) after induction therapy. Factors associated with the achievement of complete remission (CR) and overall mortality were analyzed using logistic regression and Cox proportional hazards models, respectively. Results: A total of 74 patients were analyzed. The median age was 72.8 years (range, 65-85). Nine patients (12%) had an ECOG performance status of 3-4. The most common AML subtype was AML with myelodysplasia-related changes (n=30, 41%) followed by AML with maturation (n=11, 15%). Twenty patients (27%) were previously diagnosed with myelodysplastic syndromes (MDS). According to the 2017 ELN stratification, 3 patients (4%) were classified as favorable-risk, 44 (60%) as intermediate-risk, and 27 (37%) as adverse-risk. Overall, 21 patients (28%) achieved CR after induction therapy. Among 53 patients with induction failure, 37 received reinduction therapy and 14 (38%) achieved CR. The ELN favorable- or intermediate-risk (OR, 23.2; 95% CI, 4.59-117.0, p&amp;lt;0.001) and age under 70 years (OR, 7.62; 95% CI, 1.54-37.8, p=0.013) were important factors associated with the achievement of CR. Median OS was 10.3 months for all patients and 19.3 months for patients who achieved CR after induction therapy. The probability of 3-year survival was 20.9% in the total patients. The day 100 and 1-year NRM incidences were 4% and 8%, respectively. In multivariate analysis, lower performance status (3-4) (HR, 3.93; 95% CI, 1.81-8.49, p&amp;lt;0.001), age 70 and older (HR, 3.38; 95% CI, 1.76-6.47, p&amp;lt;0.001), the ELN adverse-risk (HR, 3.16 95% CI, 1.83-5.47, p&amp;lt;0.001), and previous MDS diagnosis (HR=2.36, 95% CI=1.29-4.30, p&amp;lt;0.001) were the significant independent prognostic factors for poor OS. On the basis of the number of these four factors, the prognostic score was calculated for each patient and patients were categorized into five groups (score 0-4). The score was significantly correlated with OS (p&amp;lt;0.001, Figure). The probability of 1-year survival was 85.7% for score 0, 59.4% for score 1, and 5.9% for score 2. All patients for score 3 and 4 died within 1 year and their median OS was 2.8 months for score 3 and 0.4 months for score 4. Conclusions: Each two patient (age, performance status) and disease (ELN disease risk, history of MDS) factors were significantly associated with survival in elderly patients with AML. The prognostic scoring system based on the four factors clearly stratified survival, suggesting that it will be useful for making a treatment decision. Further large-scale studies are required to validate this system and a combination therapy with molecular targeted drugs should be established for patients with poor prognosis. Disclosures Seo: Janssen Pharmacuetical K.K.: Consultancy; Novartis: Speakers Bureau; Bristol Myers Squibb K.K.: Speakers Bureau; Meiji Seika Pharma.: Speakers Bureau. Ichikawa:Novartis, Takeda: Honoraria. Mitani:KYOWA KIRIN: Consultancy, Research Funding; CHUGAI: Research Funding; Takeda: Research Funding.

Comparison of Salvage Chemotherapy Regimens in Relapsed/Refractory Acute Myeloid Leukemia

BackgroundInduction therapy for acute myeloid leukemia (AML) with a cytarabine-anthracycline regimen (7+3) is well-established; however, there is no standard salvage therapy for patients with relapsed/refractory AML (RR-AML). There is a paucity of data regarding outcomes with salvage regimens in RR-AML that include cladribine, cytarabine, and filgrastim with mitoxantrone (CLAG-M) or without mitoxantrone (CLAG), and mitoxantrone, etoposide, and cytarabine (MEC). We compared outcomes of patients receiving CLAG-M, CLAG or MEC as salvage therapy for RR-AML.MethodsA multi-center retrospective study was conducted, including 146 adult RR-AML patients who underwent salvage therapy at the University of Wisconsin and Medical College of Wisconsin from 2009 to 2018. Demographic, clinical and pathologic factors were ascertained at the time of RR-AML diagnosis. The Center for International Blood and Marrow Transplant Research (CIBMTR) response criteria were used. Refractory AML was defined as failure to achieve remission after one or more courses of induction chemotherapy. Minimal residual disease (MRD)-negative was defined by the absence of leukemic cells by morphology and flow cytometry (<0.01%). Data were analyzed using SPSS version 21 (SPSS Inc, Chicago, IL). Bivariate analyses, using chi-square and t-test, and logistic regression analyses were performed for baseline characteristics and response to salvage chemotherapy. Kaplan-Meier analyses, using the log-rank test, were conducted. Cox regression analyses were used to correlate factors with OS. Hazard ratios (HR) with 95% CI were obtained. Statistical significance was considered at P<0.05.ResultsThe study included 146 patients with relapsed (57.5%, n=84) or refractory (42.5%, n=62) AML who received CLAG-M (51%, n=74), MEC (39%, n=57) or CLAG (10%, n=15) salvage chemotherapy. Baseline characteristics were similar between the three groups (all P>0.1). Median age was 60 years (range 22-77 years) and 59% patients were male. AML was classified according to WHO 2016 guidelines as AML with recurrent genetic abnormalities (23%), myelodysplasia (MDS)-related AML (25%), therapy-related AML (8%) and AML not otherwise specified (44%). Cytogenetics were good (5%), intermediate (60%) and poor (36%) with normal (41%), complex (25%), trisomy (8%) and monosomy 5 or 7 (5.5%) being common karyotypes. Among those who had molecular testing (n=119), NPM1 and FLT3-ITD were reported in 21% and 20% patients respectively. AML risk status was good (16%), intermediate (32%) and poor (52%), based on cytogenetic and molecular abnormalities as per ELN 2017 and NCCN 2018 guidelines. Extramedullary disease was present in 13% patients. Prior hematopoietic stem cell transplant (HSCT) was performed in 13% patients. Median lab values prior to salvage regimen were: hemoglobin 9.1 g/dL, platelets 49 K/uL, leukocytes 2.5 K/uL, LDH 231 U/L and bone marrow myeloblasts 28%. Overall response rate was 49% (CLAG-M 55%, n=41/74; MEC 44%, n=25/57, CLAG 40%, n=6/15) with complete remission (CR) rate of 46% (CLAG-M 54%, MEC 37%, CLAG 40%) [P=0.140]. Three percent patients (n=5; CLAG-M=1, MEC=4) had CR with incomplete hematologic recovery (CRi). MRD analysis was available for 83 patients and a trend was seen in MRD-negative CR rates favoring CLAG-M (44%) over MEC (25%) or CLAG (17%) [P=0.128]. Sixty-six patients (45%) received subsequent HSCT (CLAG-M 50%, n=37/74; MEC 44%, 25/57; CLAG 27%, n=4/15) [P=0.245]. At last follow-up, 34% patients were in CR (CLAG-M 42%, MEC 28%, CLAG 20%) [P=0.120]. Fifty (34%) patients were alive at last follow-up (CLAG-M 46%, MEC 23%, CLAG 20%) [P=0.010]. Median OS was 9.7 months (95% CI 6.8-12.6) that was significantly better with CLAG-M (13.3 months, 95% CI 2.4-24.3) compared to MEC (6.9 months, 95% CI 2.9-10.9) or CLAG (6.2 months, 95% CI 2.4-12.6) [P=0.025] Figure 1. In multivariate model adjusted for age, gender and refractory vs relapsed AML, MEC (HR 1.75, 95% CI 1.13-2.71, P=0.013) and CLAG (HR 1.97, 95% CI 1.02-3.79, P=0.043) regimens had worse OS compared to CLAG-M. After adjusting for age, gender, refractory vs relapsed AML and HSCT, CLAG-M remained independent predictor of better OS (HR 0.64, 95% CI 0.42-0.97, P=0.037).ConclusionCLAG-M compared to MEC or CLAG is associated with significantly better OS in RR-AML regardless of age, refractory vs relapsed AML and HSCT. Our findings support the use of CLAG-M as a preferred salvage regimen for RR-AML. [Display omitted] DisclosuresAtallah:Novartis: Consultancy; BMS: Consultancy; Jazz: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy.

Mitoxantrone, etoposide, and cytarabine combination therapy for acute myeloid leukemia patients failing to achieve a complete remission after induction chemotherapy: a single-center experience

Optimal salvage chemotherapy has not been established for patients with acute myeloid leukemia (AML) who fail to attain complete remission (CR) after one course of induction chemotherapy. This retrospective study aimed to assess the efficacy and safety of an MEC (mitoxantrone, 6 mg/m2, 1-3 days; etoposide, 80 mg/m2, 1-6 days; cytarabine, 1 g/m2, 1-6 days) regimen in patients with AML who failed to attain CR after one course of induction chemotherapy. Twenty-four patients were included in this study (median age, 58 years; range, 28-79 years). After one course of MEC, 11 patients (45.8%) attained CR. Febrile neutropenia was observed in all patients, and acute infection was observed in 7 patients (29.2%). However, no therapy-related death occurred. All patients eligible for transplantation and who attained CR after MEC salvage chemotherapy underwent allogeneic hematopoietic stem cell transplantation. The MEC regimen exhibited a good response rate with tolerable adverse events. Therefore, the MEC regimen can be safely used as a salvage treatment for patients with AML who failed to attain CR after one course of induction chemotherapy.

Is Intermediate-Dose Cytarabine a Good Control for Patients with Relapsed or Refractory Acute Myeloid Leukemia?

Intermediate dose cytarabine (IDAC) defined by daily intravenous bolus of 1g/m² during 5 days has been recently defined as the standard control arm in phase 3 placebo-controlled randomized trials for patients with relapsed or refractory acute myeloid leukemia (R/R AML). In these trials assessing clofarabine/IDAC (CLASSIC-1 study, Faderl S et al., JCO 2012) or vosaroxin/IDAC (VALOR study, Ravandi F. et al., Lancet Oncol 2015) vs placebo/IDAC, complete remission rates and median overall survival with placebo/IDAC were 17.8%/18.9% and 6.3/6.1 months in the CLASSIC-1 and VALOR studies, respectively. However, the dose-intensity of this IDAC regimen remains questioned in routine practice since many centers still use higher doses of cytarabine often in combination with an anthracycline and a third drug including fludarabine, etoposide or gemtuzumab ozogamycin (FLAG-ida, MEC or MIDAM regimen for example) although these regimen have proved little efficacy and higher toxicity. We assessed the outcome of R/R AML patients that fulfilled main VALOR inclusion criteria consecutively treated in our center with intensive salvage regimen.All patients with a diagnosis of AML in first relapse or with refractory disease were eligible for this study. Acute promyelocytic leukemia were excluded. Relapse was defined as re-emergence of at least 5% leukemia blasts in bone marrow or at least 1% blasts in peripheral blood 90 days to 24 months after first complete remission or complete remission with incomplete platelet recovery. Refractory AML was defined as persistent disease at least 28 days after initiation of induction therapy, or relapse less than 90 days after first complete remission (CR) or CR with incomplete platelet recovery (CRi). All patients have received previous induction therapy with an anthracycline. Salvage regimen used were mainly cytarabine 3 g/m²/12h, d1-4 plus idarubicine 12 mg/m²/d, d1-3 or dauno 60 mg/m²/d, d1-2 or amsacrine 200 mg/m²/d, d1-3; less frequently MiDAM (mitoxantrone 12mg/m² d1-3, cytarabine1 g/m²/12h d1-5, GO 4-6mg/m², d4) or FLAG-Ida. Cytarabine dose for patients >60 was reduced to 1g/m²/12h, d1-5.We found, in our database, 151 R/R AML according to VALOR criteria treated between 2000 and 2013: 72 patients (48%) had refractory diseases (primary refractory: n=60, 40% and relapse less than 90 days after CR: n=12, 8.0%) and 79 (52%) had relapsed (early relapse more than 90 days after CR and less than one year: n=52, 66%; late relapse between one and two years: n=27, 34%). Patients characteristics were as follows: 85 (56%) were male, median age was 48 years (interquartile range [IQR], 36-60.5; 38 (27%) were 60 years or older). Cytogenetics at diagnosis was favorable in 18 (12%); intermediate in 93 (62%); adverse in 38 (25%) or unknown in 2 (1%) patients, respectively. They were treated as first line therapy with one (42%) or two cycles (58%). Early death rates at day 30 and day 60 were 7% and 17% in the whole cohort; 6% and 12% in younger patients and 12% and 29% in patients 60 years or older. Combined CR rate (defined as CR and CRi) was 53% for the whole cohort, and 57%/42%/56%/52%/63%/50% for <60 years/≥60 years/relapses/early relapses/late relapses/refractory diseases respectively. Allogeneic-SCT was performed in 25 out of 80 patients (31%) having achieved CR after salvage treatment. Median overall survival (OS) was 8 months for the whole cohort and 9.2/5.0/7.7/7.5/13.6/9.2 months for <60 years/≥60 years/relapses/early relapses/late relapses/refractory diseases respectively.Using VALOR inclusion criteria, age is the main factor that discriminate R/R AML patients selected for clinical trials using IDAC as control arm compared to patients of daily practice. Thus, those patient populations remain hardly comparable. However, as far as CR is concerned, IDAC seems suboptimal as compared to higher-intensity regimen used in daily practice. Yet, this higher CR rates do not translate into a significant gain in survival since median OS remains close to that of IDAC with the possible exception of refractory patients who seem to benefit from higher-intensity regimen. Thus, although unsatisfactory, IDAC could be considered as a fair control arm for overall survival endpoint especially in patients older than 60 year of age. [Display omitted] DisclosuresTavitian:Novartis: Membership on an entity's Board of Directors or advisory committees. Huguet:Pfizer, Novartis, BMS, Ariad, Jazz, Amgen: Membership on an entity's Board of Directors or advisory committees. Recher:Celgene, Sunesis, Amgen, Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene, Sunesis, Amgen, Novartis, Chugai: Research Funding.

Control of Nausea and Vomiting in Patients with Colorectal Cancer Receiving Chemotherapy with Moderate Emetic Risk

Chemotherapy with moderate emetic risk (MEC), including irinotecan-based and oxaliplatin-based chemotherapy regimens, are predominantly used for colorectal cancer chemotherapy. Chemotherapy-induced nausea and vomiting (CINV) remain unsatisfactorily controlled. The rates of prevalence of antiemetic medication and the control of CINV were investigated from medical records in patients with colorectal cancer who received the first cycle of irinotecan-based or oxaliplatin-based regimens. Risks for CINV were determined by multivariate logistic regression analysis. A total of 179 patients received the first cycle of MEC regimens and the number of overall cycles was 2,176 during the study period from January 2013 to December 2015. Guideline-consistent antiemetic medication was performed in most cases. The rate of no-CINV was nearly 90% during the overall period. Female sex and age under 50 years were significant risks for CINV. Comparison considering only the group aged 50 years or more indicated that the control of CINV was significantly worse in irinotecan-based regimens than in the oxaliplatin-based regimens. Female sex and age younger than 50 years were significant risks for CINV in patients receiving MEC for colorectal cancer. Moreover, the control of CINV was less sufficient for irinotecan-based than for oxaliplatin-based regimens.

Safety and efficacy of NEPA, an oral fixed combination of netupitant and palonosetron, in older patients.

Prevention of chemotherapy-induced nausea and vomiting is critical in older patients with cancer. NEPA is an oral fixed combination of netupitant 300mg, a new NK1 receptor antagonist (RA), and palonosetron 0.5mg, a pharmacologically distinct 5-HT3 RA. This retrospective analysis evaluated the efficacy and safety of NEPA in older patients. Patients aged ≥65 and ≥70years from one phase II and two phase III trials were considered. Chemotherapy-naive patients with malignant tumors were treated with anthracycline-cyclophosphamide (AC), non-AC-based moderately emetogenic chemotherapy (non-AC MEC), or highly emetogenic chemotherapy (HEC). Following single-dose NEPA, patients received oral dexamethasone on day 1 (AC and non-AC MEC) or days 1-4 (HEC). Efficacy was evaluated through complete response (CR) in cycle 1. Safety was evaluated by AEs and ECGs. Data were summarized by descriptive statistics. Overall, 214 patients were ≥65years and 80 were ≥70years. A higher CR was observed in older patients versus the total population; in the acute phase >90% of patients ≥65years experienced CR. Efficacy was maintained over multiple cycles of chemotherapy. No significant nausea rates were generally higher in the older patients versus total population. Similar rates of AEs in the first treatment cycle were reported for patients ≥65years, ≥70years, and total population (72.9% vs 67.5% vs 70.0%, respectively). No cardiac safety concerns were raised. NEPA is highly effective in older patients receiving MEC or HEC regimens. NEPA is also well tolerated, demonstrating suitability for use in older patients who may have comorbidities.

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] &lt; 5 mm), no significant nausea (maximum VAS &lt; 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 (&gt; 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 &lt; 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]

1453P - Antiemetic prophylaxis (AP) in our clinical practice: are we doing it right?

In recent years several national and international guidelines about AP have been drafted; they suggest a different AP according to chemotherapeutic agents' emetic potential (that is, high [HEC], AC/EC regimen, moderate [MEC], low [LEC], or minimal [mEC]). We then decide to perform a survey to assess our adherence to these recommendations. We analysed AP prescribed to our patients (pts) who underwent chemotherapy (CT), both oral and intravenous, during 5 days in our Day Hospital Service. We compared it to 2016 MASCC Guidelines with the exception of carboplatin, which was still considered MEC (although the recent “upgrade” to HEC). We analysed 322 pts, of which 11 (3.4%), 11 (3.4%), 99 (30.8%), 126 (39.1%), and 75 (23.3%) received HEC, AC/EC, MEC, LEC, and mEC regimens, respectively. 82 pts (25.5%) received appropriate AP, whereas 240 (74.5%) had an inconsistent AP. Among HEC regimens, only 9.1% of pts received correct AP, whereas 91.9% had a wrong AP (70% in both acute and delayed AP). For AC/EC schemes, 100% pts received inconsistent AP, of which 36.4% in delayed AP, and 63.6% in both acute and delayed AP. Among MEC schemes, 96% pts received an inconsistent AP (45.3% in delayed AP, and 53.7% in both). For LEC schemes, 93.6% pts received inconsistent AP, among which 96.6% in acute AP. In mEC regimens, 92% pts received inconsistent AP (of which 66.6% in acute AP). The main errors are the abuse of corticosteroids, mainly in the acute AP (46.3% of all pts), and of anti-5HT3 (35.1%).Tabled 1Total (%)HEC (%)AC/EC (%)MEC (%)LEC (%)mEC (%)Consistent25.59.1046.392Inconsistent, of which: - Only acute - Only delayed - Both acute and delayed74.5 49.6 21.2 29.290.9 0 30 70100 0 36.4 63.696 1 45.3 53.793.6 96.6 0 3.48 66.6 16.7 16.7 Open table in a new tab Although the existence of specific AP guidelines, there is still a lack of adherence to evidence-based literature, both in the way of under- and over-prescription. This underlines the need of implementing education for healthcare professionals and usage of informatics tools for antiemetic therapies in everyday clinical practice to reduce inconsistencies and to increase adherence to guidelines.

Chemotherapy-induced nausea and vomiting in Italian cancer centers: results of CINVDAY, a prospective, multicenter study.

Guideline consistency in the prevention of chemotherapy-induced nausea and vomiting (CINV) remains low (29% in the Pan European Emesis Registry study) and very low (11%) in regimens with a high emetogenic risk. The aim of this study was to evaluate the guideline consistency of CINV prophylaxis for acute emesis in daily clinical practice in Italy. This was a prospective, observational, multicenter study. Patients scheduled to receive antitumor treatment on a single prespecified day were included. Data on patient characteristics (demographic and clinical), type of anticancer therapy, and type of antiemetic therapy prescribed for acute emesis were collected on electronic data capture forms. Chemotherapy regimens and antiemetic prophylaxis were categorized according to the MASCC 2011 guidelines. The study was approved by the local ethics committees. From July 2013 to February 2014, a total of 502 patients were enrolled at 26 study sites. Median age was 62 years (range 27-87 years). Colorectal cancer and breast cancer were the most common malignancies. The emetogenic potential of the chemotherapy regimens used was high (HEC) (23.7%), moderate (MEC) (40.6%), low (31.3%) or minimal (4.4%). Overall, guideline consistency was 19.3%. Consistency reached 45% when the various 5HT3 receptor antagonists were considered equivalent and interchangeable in MEC regimens. Adherence to guidelines was lowest for MEC and Minimal risk groups. Ten percent of patients in HEC and MEC regimens did not receive any 5HT3 receptor antagonists. NK1 receptor antagonists were used in 8% of all regimens. Our study indicates that antiemetic guideline inconsistency remains an issue in daily clinical oncology practice in Italy.

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in non–anthracycline/cyclophosphamide (AC)-based moderately emetogenic therapy (MEC).

209 Background: Rolapitant, a novel NK-1 receptor antagonist, showed efficacy in CINV prevention in patients (pts) receiving MEC (anthracycline/cyclophosphamide (AC) and other regimens) in a global phase 3 trial. Recent anti-emetic guidelines consider AC based regimens to be highly emetogenic. In this post hoc analysis, the efficacy and safety of rolapitant was assessed in Cycle 1 in pts receiving non-AC MEC, and in the subset of pts receiving carboplatin-based MEC. Methods: In a double-blind, active-controlled study, pts were randomized to oral rolapitant 180 mg or placebo 1–2 hours before MEC. All pts received granisetron 2 mg oral on days 1-3 and oral dexamethasone 20 mg on day 1. Complete response (CR = no emesis + no use of rescue medication), no emesis, and no nausea were assessed in overall (0-120 h), acute (0-24 h), and delayed ( &gt; 24-120 h) phases. Results: CR was significantly (P &lt; 0.01) higher with rolapitant than active control in overall and delayed phases in the carboplatin subset and in all 3 phases in the non-AC population (Table). No emesis rates were significantly (p &lt; 0.05) higher with rolapitant in the carboplatin subset in the overall phase. No nausea rates were significantly (P &lt; 0.05) higher with rolapitant in the overall and delayed phases in carboplatin-based MEC. Incidences of treatment-related AEs in Cycle 1 with rolapitant vs. active control were 11.3% vs. 6.7% in the carboplatin-based subset. Most common AEs with rolapitant and active control were constipation, fatigue, and headache. Conclusions: Rolapitant was superior to active control in preventing CINV in pts receiving non-AC MEC, including in the subgroup receiving carboplatin. Rolapitant was well tolerated with low incidence of AEs. Clinical trial information: NCT01500226. [Table: see text]

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in moderately emetogenic therapy (MEC).

9622 Background: Rolapitant, a novel NK-1 receptor antagonist, showed efficacy for prevention of CINV in patients (pts) receiving MEC (anthracycline/cyclophosphamide (A/C) and other regimens) in a ...

Open-label observational study to assess the efficacy and safety of aprepitant for chemotherapy-induced nausea and vomiting prophylaxis in Indian patients receiving chemotherapy with highly emetogenic chemotherapy/moderately emetogenic chemotherapy regimens.

Context:Currently, there is limited data on the prevention of chemotherapy-induced nausea and vomiting (CINV) in Indian population with aprepitant containing regimens.Aims:The aim was to assess the Efficacy and Safety of Aprepitant for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy/moderately emetogenic chemotherapy (HEC/MEC) regimens.Settings and Design:Investigator initiated, multicentric, open-label, prospective, noncomparative, observational trial.Subjects and Methods:Triple drug regimen with aprepitant, palonosetron, and dexamethasaone administration was assessed for the prevention of CINV during acute, delayed, and the overall phase (OP) for HEC/MEC Regimens. The primary endpoint was complete response (CR; no emesis and no use of rescue medication) and the key secondary endpoint was the complete control (CC; no emesis, no rescue medication and no more than mild nausea) during the OP.Statistical Analysis Used:Perprotocol efficacy was analyzed for the first cycle with results represented in terms of CR/CC rates using descriptive statistics.Results:Seventy-five patients were included in the study with median age of 49.7 years and 89.7% being females. The CR rate (OP) for patients administered HEC or MEC regimens during the first cycle were 92% and 90.9%, respectively. Similarly, the CC rates (OP) were 75% and 90% for these regimens, respectively. 7 (9.2%) patients reported adverse drug reactions that were mild and transient with no reports of any serious adverse events.Conclusions:Use of aprepitant containing regimen for patients receiving HEC/MEC regimen resulted in significantly high CR and CC response rates, which further consolidate its potential role to improve patient quality of life and compliance to disease management.

Cardiac safety of a granisetron transdermal system in the treatment of chemotherapy-induced nausea and vomiting.

e19601 Background: Granisetron, a 5-HT3 antagonist, is widely used as an antiemetic. However, 5-HT3 antagonists may have cardiac effects, as shown by the withdrawal of IV dolesetron for treatment of chemotherapy-induced nausea and vomiting (CINV) in the US owing to risk of cardiac effects. Such effects are a concern, as chemotherapy and radiotherapy can cause acute dysrhythmias and longer-term cardiac damage. Granisetron Transdermal System (GTDS, Sancuso) is approved in the US for prevention of CINV in patients receiving up to 5 days of moderately or highly emetogenic (MEC, HEC) consecutive chemotherapy. GTDS is applied 24–48 hours prior to chemotherapy and can be left in place up to 7 days. Because of the novel delivery and altered pharmacokinetic profile of granisetron in the GTDS compared with IV or oral delivery, cardiac safety was investigated in a phase III clinical trial and a phase I QTc cardiac safety study. Methods: In a randomized, double-blind, phase III trial of GTDS vs oral granisetron in multiday MEC and HEC regimens, patients had sequential 12-lead ECG readings at baseline, at start of chemotherapy (coinciding with the estimated granisetron maximum plasma concentration [Cmax]), and at 120 hours post treatment. In a blinded placebo-controlled phase I QTc study, healthy subjects received GTDS, placebo, or active control. The primary end point was time-matched, placebo-corrected change from baseline in QTc based on the Fridericia correction (ddQTcF), allowing exclusion ≥10 ms increases at the 95% CI level, tested at 3 or more time points around the granisetron Cmax. Results: In the phase III trial, there were no clinically relevant changes in repolarization intervals, ECG morphology, or heart rate in the GTDS group (n=273). In the phase I QTc study, mixed-effects modeling showed a maximum ddQTcF in the GTDS group (n=60) of 1.9 ms on day 3 and 2.5 ms on day 5, excluding any change ≥10 ms at the 95% CI level. Conclusions: In a phase III trial in patients receiving chemotherapy and GTDS, no cardiac safety issues emerged. This finding was supported by a phase I QTc study of GTDS in healthy subjects that showed no significant QTc prolongation at standard regulatory and clinical thresholds.

Salvage chemotherapy regimens for acute myeloid leukemia: Is one better? Efficacy comparison between CLAG and MEC regimens

There is no standard salvage regimen for AML. We retrospectively compared two commonly used regimens at our institution: CLAG and MEC. The complete response rate (CR) was 37.9% for CLAG ( n = 97) and 23.8% for MEC ( n = 65) ( P = 0.048), with median overall survival (OS) of 7.3 and 4.5 months, respectively ( P = 0.05). In primary refractory disease, CR was 45.5% for CLAG and 22.2% for MEC ( P = 0.09), with median OS of 11 and 4.5 months, respectively ( P = 0.07). In first relapse, CR was 36.8% and 25.9% ( P = 0.35) and median OS was 6.7 and 6.7 months, respectively ( P = 0.87). Our data support use of CLAG for RR-AML.

Salvage Chemotherapy Regimens for Acute Myeloid Leukemia: Is One Better?.

Abstract 1022Poster Board I-44 Background:The vast majority of acute myeloid leukemia (AML) patients will relapse after initial therapy. Allogeneic hematopoietic cell transplant (AHCT) remains the only curative option in relapsed or refractory (RR)-AML. Currently, there is no standard or preferred regimen in the salvage setting. Regimens combining cladribine, high dose cytarabine and G-CSF (CLAG), or etoposide, cytarabine and mitoxantrone (MEC) in RR-AML yield complete remission (CR) rates of 50% and 66%, respectively (Wrzesieñ-Kuœ 2003, Amadori 1991). We hereby compare the efficacy of treatment with the CLAG and MEC regimens in RR-AML. Methods:A retrospective non-randomized comparison was performed for RR-AML patients who received CLAG or MEC regimens. The CLAG regimen consisted of: cladribine 5mg/m2/day IV on days 2-6, cytarabine 2gm/m2/day IV days 2-6 and filgrastim 300mcg daily on days 1-6. The MEC regimen included mitoxantrone 8mg/m2/day IV on days 1-5, etoposide 100mg/m2/day IV on days 1-5, cytarabine 1gm/m2/day IV on days 1-5. Data collected included baseline demographics and disease characteristics such as AML subtype, cytogenetics, duration of remission, prior therapies, response rates and overall survival (OS). The primary objective was to compare CR rates between the two regimens; the secondary endpoint was OS. International Working Group criteria were used to define CR. Primary refractory AML (PR-AML) in this study was defined as failure to achieve CR1 and less than 50% reduction in myeloblasts after first line of induction. All analyses were conducted using SPSS version 15.0. (SPSS Inc, Chicago, IL). The Kaplan–Meier method was used to estimate median overall survival; chi-square test was used for comparison of categorical variables and t-test for continuous variables. Log rank test was used to compare Kaplan–Meier survival estimates between two groups. Results:Between January 2005 and June 2008, 162 patients were treated with CLAG or MEC for RR-AML. Patient baseline characteristics were similar between the two groups with respect to age, sex, FAB subtype, antecedent hematological disease history, cytogenetics, and prior therapy. The regimens were used as salvage for either PR- AML, or relapsed disease. Overall CR rates were CLAG, 38% (35/87) and MEC, 24% (15/63) (p= 0.048). The OS was 7.3 months for CLAG and 4.47 months for MEC, p=0.047. The mean length of stay was 31.2 vs. 32.5 days (range 2-107 days) respectively. For patients who received those regimens for PR-AML (n=55). No difference in the mean myeloblasts% at diagnosis or at time of reinduction was observed between the two regimens. CR rates were 45.5% (15/33) for CLAG and 22.2% (4/18) for MEC, p= 0.09. More patients treated with MEC (55.6%) had residual disease after treatment compared to CLAG (21.2%), (p=0.03). The median OS for the PR-AML patients who received CLAG was 10.97 months vs. 4.47 months for MEC (p=0.068). For Patients who were treated at time of first relapse (n=70), CR rates were CLAG, 36.8% (14/42) and MEC, 25.9% (7/28) (p=0.354). The OS in first relapse was similar between the two arms: CLAG 6.7 months and MEC 6.73 months (p=0.87). Among RR-AML patients ≤ 65 years, 36% of patients who received CLAG proceeded to AHCT compared to 25% with MEC. Conclusion:In this retrospective analysis, the CLAG regimen yielded significantly higher CR rates compared to MEC in RR-AML. There was a trend for improved OS particularly in the primary refractory setting, where CLAG regimen showed an additional OS benefit of 6.5 months. The higher CR rates and superior DFS and OS are clinically significant, supporting the use of CLAG as a preferred regimen for RR-AML patients. Disclosures:Off Label Use: CLAG and MEC regimens for AML.