Anthracycline-cyclophosphamide Research Articles

Abstract PO2-16-09: Dose-dense versus 3-weekly AC during Neoadjuvant Chemoimmunotherapy for Early-Stage Triple-Negative Breast Cancer (TNBC): a Real-World Safety and Efficacy Data Analysis

Abstract Background: The Keynote-522 (KN-522) study established the use of pembrolizumab in combination with neoadjuvant carboplatin-paclitaxel, followed by 3-weekly (3w) anthracycline-cyclophosphamide (AC), as the standard of treatment for stage II-III TNBC. However, dose-dense chemotherapy (CT) improves survival rates compared to the standard schedule in early-stage breast cancer and several groups have been modifying the KN-522 regimen with dose-dense AC (ddAC). The objective of this study was to compare the safety and effectiveness of ddAC versus the q3w schedule. Methods: We conducted a multicentric real-world analysis of patients (pts) with early-stage TNBC who received neoadjuvant CT plus pembrolizumab at nine cancer centers. Safety endpoints included grade ≥ 3 adverse events (AEs), drug discontinuation, hospitalization due to AEs, and the use of antibiotics during neoadjuvant therapy. Pathologic complete response (pCR) was used as the effectiveness endpoint, and we performed univariate and multivariable logistic regression to evaluate factors associated with pCR. Results: To date, we included 168 pts in this study of which 137 pts have finished the neoadjuvant therapy phase and constituted our safety cohort. Among them, 86 pts (62.8%) received ddAC and 51 pts (37.2%) were treated with the 3w schedule. The two groups exhibited no significant differences in baseline characteristics; the median age was 42 years (range 29 - 75), 70.8% had stage II and 25.5% had stage III TNBC, 46.7% had positive lymph nodes, and 74.4% had a Ki67-index ≥ 50%. Overalls, 30.2% and 27.4% presented grade ≥ 3 AEs with ddAC and 3w AC, respectively, with no significant difference between the two groups (p=0.177). Grade ≥ 3 immune-related AEs (irAEs), occurred in 8.1% with ddAC and 3.9% with 3w AC (0.335). The most common grade ≥ 3 irAEs were pneumonitis (n=4) and hepatitis (n=2). The ddAC group had a higher rate of any drug discontinuation due to toxicities (24.4% vs. 11.8%, p=0.043) and a greater use of antibiotics (27.9% vs. 11.8%, p=0.009) compared to the 3w group. There was a trend toward more rates of hospitalization due to AEs in the ddAC group, although this was not statistically significant (17.4% vs 11.8%, p=0.131). At the time of data analysis cutoff, a total of 119 pts underwent surgery and have pathology report available and were included in the efficacy cohort. In the univariate analysis, the pCR rates were 65.8% with ddAC and 55.8% with 3w AC (OR 1.52, 95% CI 0.70-3.27, p=0.282). The rates of RCB (residual cancer burden) 0-1 were 81.2% and 67.6%, respectively (OR 2.06, 95% CI 0.82 – 5.16, p=0.120). Factors influencing rates of pCR were Ki67 index ≥ 50% and tumor staging, which remained significant in the multivariable analysis (Table). In the 3w AC group, no difference in pCR was observed between pts who used or not granulocyte colony stimulating-factors (61.1% vs 52%, p=0.553). Conclusion: No difference in grade ≥ 3 AEs was observed between ddAC and 3w AC in pts with early-stage TNBC receiving neoadjuvant CT plus pembrolizumab. Nevertheless, the dose-dense regimen was linked to higher rates of drug discontinuation and antibiotic use. Although the pCR rates numerically favored ddAC, the difference was not statistically significant. Thus, the medical community should consider carefully risks and benefits of using ddAC within the KN522 regimen. Larger studies and longer follow-up are warranted to assess the long-term outcomes of the CT schedules. Multivariable regression of factors associated with pCR Citation Format: Renata Colombo Bonadio, Fernanda Madasi, José Bines, Rafael Ferreira, Daniela Rosa, Candice Santos, Zenaide Souza, Daniele Assad-Suzuki, Julio Araujo, Débora Gagliato, Carlos dos Anjos, Bruna Zucchetti, Anezka Ferrari, Mayana Lopes, Renata Cangussu, Maria Marcela Monteiro, Paulo Hoff, Laura Testa, Romualdo Barroso-Sousa. Dose-dense versus 3-weekly AC during Neoadjuvant Chemoimmunotherapy for Early-Stage Triple-Negative Breast Cancer (TNBC): a Real-World Safety and Efficacy Data Analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-16-09.

Adherence to antiemetic guidelines in solid cancer patients receiving highly emetogenic chemotherapy in Korea.

Highly emetogenic chemotherapy (HEC) is known to induce nausea and vomiting (CINV) in approximately 90% of cancer patients undergoing this regimen unless proper prophylactic antiemetics are administered. This study aimed to analyze the use of a three-drug prophylactic antiemetic regimen during the first cycle of chemotherapy and assess the compliance rate with the National Comprehensive Cancer Network (NCCN) guidelines. This retrospective study utilized data from the National Inpatient Sample database from 2016 to 2020 provided by the Health Insurance Review and Assessment Service. The claims data encompassed 10 to 13% of inpatients admitted at least once each year. Patients with solid cancers treated with two HEC regimens, namely anthracycline + cyclophosphamide (AC) and cisplatin-based regimens, were selected as the study population. We evaluated the use of a three-drug prophylactic antiemetic regimen, including a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone and compliance with the NCCN guidelines. Multiple logistic regression was conducted to estimate the influence of variables on guideline adherence. A total of 3119 patients were included in the analysis. The overall compliance rate with the NCCN guidelines for prophylactic antiemetics was 74.3%, with higher rates observed in the AC group (87.9%) and lower rates in the cisplatin group (60.4%). The AC group had a 6.37 times higher likelihood of receiving guideline-adherent antiemetics than the cisplatin group. Further analysis revealed that, compared to 2016, the probability of complying with the guidelines in 2019 and 2020 was 0.72 times and 0.76 times lower, respectively. This study showed that a considerable proportion of HEC-treated patients received guideline-adherent antiemetic therapies. However, given the variations in adherence rates between different chemotherapy regimens (AC vs. cisplatin), efforts to improve adherence and optimize antiemetic treatment remain essential for providing the best possible care for patients experiencing CINV.

Changes in vascular function and correlation with cardiotoxicity in women with newly diagnosed breast cancer undergoing HER2-directed therapy with and without anthracycline/cyclophosphamide.

The objective of this study was to assess the effect of HER2-directed therapy (HER2-Tx) on peripheral vasoreactivity and its correlation with cardiac function changes and the additive effects of anthracycline/cyclophosphamide (AC) therapy and baseline cardiovascular risk. Single-centre, prospective cohort study of women with newly diagnosed stage 1-3 HER2-positive breast cancer undergoing HER2-Tx +/- AC. All participants underwent baseline and 3-monthly evaluations with Endo-Peripheral Arterial Tonometry (Endo-PAT), vascular biomarkers [C-type natriuretic peptide (CNP) and neuregulin-1 beta (NRG-1β)], and echocardiography. Cardiotoxicity was defined as a decrease in the left ventricular ejection fraction (LVEF) of >10% to a value <53%. Of the 47 patients enrolled, 20 (43%) received AC in addition to HER2-Tx. Deterioration of reactive hyperaemia index (RHI) on Endo-PAT by ≥20% was more common in patients receiving HER-Tx plus AC than HER2-Tx alone (65% vs. 22%; P = 0.003). A decrease in CNP and log NRG-1β levels by 1 standard deviation did not differ significantly between the AC and non-AC groups (CNP: 20.0% vs. 7.4%; P = 0.20 and NRG-1β: 15% vs. 11%; P = 0.69) nor did GLS (35% vs. 37%; P = 0.89). Patients treated with AC had a significantly lower 3D LVEF than non-AC recipients as early as 3 months after exposure (mean 59.3% (SD 3) vs. 63.8% (SD 4); P = 0.02). Reactive hyperaemia index and GLS were the only parameters correlating with LVEF change. Combination therapy with AC, but not HER2-Tx alone, leads to a decline in peripheral vascular and cardiac function. Larger studies will need to define more precisely the causal correlation between vascular and cardiac function changes in cancer patients.

Single-dose NEPA versus an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy.

Non-inferiority of NEPA (fixed combination of NK1 receptor antagonist (RA), netupitant, and 5-HT3 RA, palonosetron) versus an aprepitant regimen was previously shown in a pragmatic study in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy (MEC). In the MEC group a numerically higher complete response (CR: no emesis, no rescue) rate was seen for NEPA during the overall 0-120 h phase (NEPA 76.1% vs. 63.1% aprepitant). As NEPA exhibits long-lasting efficacy, this study evaluated a prolonged period up to 144 h, beyond the traditional 120 h post-chemotherapy. In this post-hoc analysis we explore the comparative efficacy of NEPA versus the aprepitant regimen in the MEC group up to 144 h, while also assessing the impact of risk factors on CINV prevention. This was a pragmatic, multicenter, randomized, prospective study. Oral NEPA was administered as a single dose on day 1, while aprepitant was given on days 1-3 + ondansetron on day 1; all patients were to receive dexamethasone on days 1-4. Patients were chemotherapy-naïve and receiving MEC, with a subset evaluation of those with a risk factor for developing CINV (i.e., female, male <60 years, male ≥60 years who received carboplatin, or male ≥60 years with anxiety). CR rates were compared during the extended overall (0-144 h) phase. The MEC group included 211 patients; of these 181 were in the risk factor subset. Significantly higher CR rates were seen for NEPA than aprepitant during the extended overall phase for the total MEC group (NEPA 77.1%, aprepitant 57.8%, p = 0.003) and also in the subset of patients with CINV risk factors (NEPA 73.9%, aprepitant 56.2%, p = 0.012). A single dose of NEPA, administered on day 1 only, was more effective than a 3-day aprepitant regimen in preventing CINV for an extended duration in patients receiving MEC and in those with emetic risk factors.

Detailed Sub-study Analysis of the SECRAB Trial: Quality of Life, Cosmesis and Chemotherapy Dose Intensity

AimsSECRAB was a prospective, open-label, multicentre, randomised phase III trial comparing synchronous to sequential chemoradiotherapy (CRT). Conducted in 48 UK centres, it recruited 2297 patients (1150 synchronous and 1146 sequential) between 2 July 1998 and 25 March 2004. SECRAB reported a positive therapeutic benefit of using adjuvant synchronous CRT in the management of breast cancer; 10-year local recurrence rates reduced from 7.1% to 4.6% (P = 0.012). The greatest benefit was seen in patients treated with anthracycline–cyclophosphamide, methotrexate, 5-fluorouracil (CMF) rather than CMF. The aim of its sub-studies reported here was to assess whether quality of life (QoL), cosmesis or chemotherapy dose intensity differed between the two CRT regimens. Materials and methodsThe QoL sub-study used EORTC QLQ-C30, EORTC QLQ-BR23 and the Women's Health Questionnaire. Cosmesis was assessed: (i) by the treating clinician, (ii) by a validated independent consensus scoring method and (iii) from the patients' perspective by analysing four cosmesis-related QoL questions within the QLQ-BR23. Chemotherapy doses were captured from pharmacy records. The sub-studies were not formally powered; rather, the aim was that at least 300 patients (150 in each arm) were recruited and differences in QoL, cosmesis and dose intensity of chemotherapy assessed. The analysis, therefore, is exploratory in nature. ResultsNo differences were observed in the change from baseline in QoL between the two arms assessed up to 2 years post-surgery (Global Health Status: –0.05; 95% confidence interval –2.16, 2.06; P = 0.963). No differences in cosmesis were observed (via independent and patient assessment) up to 5 years post-surgery. The percentage of patients receiving the optimal course-delivered dose intensity (≥85%) was not significantly different between the arms (synchronous 88% versus sequential 90%; P = 0.503). ConclusionsSynchronous CRT is tolerable, deliverable and significantly more effective than sequential, with no serious disadvantages identified when assessing 2-year QoL or 5-year cosmetic differences.

Estradiol Levels and Chemotherapy in Breast Cancer Patients: A Prospective Clinical Study.

Breast cancer remains a global health issue, including in Indonesia, which has a relatively high incidence of breast cancer. Several theories have proved the role of estrogen in breast cancer carcinogenesis, but there is yet to be a preventive measure against breast cancer. Chemotherapy is one of the therapeutic modalities for breast cancer that disturbs ovarian function in producing estrogen due to damaged ovarian granulosa cells. Chemotherapy becomes an alternative option to decreasing circulating estradiol levels through interventions in ovarian functions, either by surgery, such as oophorectomy, or medications that disturb the ovarian functions. This study aimed to observe the estradiol levels in breast cancer patients before and after chemotherapy. This was a prospective cohort study. We observed the estradiol levels before and after adjuvant chemotherapy in breast cancer patients. Subjects' characteristics are presented in mean ± standard deviation, distribution frequency, and percentage. Subjects' characteristics based on chemotherapy were tested using an independent t-test, Mann-Whitney U, and Chi-square/Fisher exact test. Effects of chemotherapy on estrogen levels were tested using the Wilcoxon rank test and Kruskal-Wallis test. A total of 194 research subjects were included. There were changes in estradiol levels before and after therapy. The decrease of estradiol levels in patients who did not receive chemotherapy was -6.9% (P > 0.05). Patients who received anthracycline cyclophosphamide (AC) regimen, paclitaxel and anthracycline (TA) regimen, paclitaxel, anthracycline and trastuzumab (TA + H) regimen, and platinum regimen experienced a significant decrease in estradiol levels (-21.4% (P < 0.05), -20.2% (P < 0.001), -31.7% (P < 0.01), and -23.7% (P < 0.05), respectively). Among chemotherapy groups, the estradiol levels before and after chemotherapy did not have significant differences (P = 0.937 and P = 0.730, respectively). There are no significant differences in estradiol levels between chemotherapy and hormonal therapy groups. Patients in both groups have decreased estradiol levels after therapy, although patients in hormonal therapy do not experience as much decrease as those in chemotherapy.

Duration of Chemotherapy-Induced Nausea and Vomiting (CINV) as a Predictor of Recurrent CINV in Later Cycles.

The relationship between CINV duration and recurrence in subsequent cycles is largely unstudied. Our objective was to determine if patients experiencing CINV in their first cycle of chemotherapy (C1) would face increased risk of CINV in later cycles and whether the duration of the CINV would predict increased risk of recurrence. Using data from a previously reported phase III trial, we assessed patients' recurrence of breakthrough CINV after antiemetic prophylaxis for anthracycline+cyclophosphamide (AC) for breast cancer, comparing C1 short CINV vs. extended CINV as a secondary analysis. Complete response (CR) and CINV duration were primary and secondary endpoints, respectively. CR was considered prophylaxis success; lack of CR was considered treatment failure (TF). Among 402 female patients, 99 (24.6%) had TF in C1 (TF1). The remaining 303 patients (CR1) had ≥93% CR rates in each subsequent cycle, while the 99 patients with TF1 had TF rates of 49.8% for cycles 2-4 (P < .001). The 51 patients with extended TF (≥3 days) in C1 had recurrent TF in 73/105 later cycles (69.5%, P < .001), while the 48 patients with short TF (1-2 days) in C1 had recurrent TF in 33/108 later cycles (30.6%). The relative risk of recurrence after C1 extended TF was 2.28 (CI 1.67-3.11; P < .001) compared to short TF. Prophylaxis success in C1 led to >90% repeat success across cycles of AC-based chemotherapy. For patients with breakthrough CINV, extended duration strongly predicted recurrent CINV. The duration of CINV should be closely monitored, and augmenting antiemetic prophylaxis considered for future cycles when extended CINV occurs.

Assessing the impact of antiemetic guideline compliance on prevention of chemotherapy-induced nausea and vomiting: Results of the nausea/emesis registry in oncology (NERO)

BackgroundEvidence-based antiemetic guidelines offer predominantly consistent recommendations for chemotherapy-induced nausea and vomiting (CINV) prophylaxis. However, studies suggest that adherence to these recommendations is suboptimal. We explored inconsistencies between clinical practice and guideline-recommended treatment with a registry evaluating the effect of guideline-consistent CINV prophylaxis (GCCP) on patient outcomes. Patients and methodsThis was a prospective, non-interventional, multicentre study. The primary objective was to assess the overall (Days 1–5) complete response (CR: no emesis/no rescue use) rates in patients who received GCCP or guideline-inconsistent CINV prophylaxis (GICP) using diaries for 5 days following chemotherapy. Cycle 1 results are presented in patients who received either (1) anthracycline/cyclophosphamide (AC) highly emetogenic chemotherapy (HEC), non-AC HEC or carboplatin, with GCCP for all these groups consisting of prophylaxis with an NK1 receptor antagonist (RA), 5-HT3RA and dexamethasone prior to chemotherapy or (2) moderately emetogenic chemotherapy (MEC), with GCCP consisting of a 5-HT3RA and dexamethasone prior to chemotherapy as per MASCC/ESMO 2016 guidelines, in place at the time of the study. Results1,089 patients were part of the cycle 1 efficacy evaluation. Overall GCCP was 23%. CR rates were significantly higher (P < 0.05) in patients receiving GCCP (62.2%) versus GICP (52.6%) in the overall population, as well as in the subsets of patients receiving AC/non-AC HEC (60.2% versus 47.8%), MEC (73.8% versus 57.8%) and in those non-naïve to the chemotherapy received (65.9% versus 53.8%). No impact on daily living due to CINV (FLIE assessment) was observed in 43.4% patients receiving GCCP versus 28.5% GICP (P < 0.001). ConclusionConsistent with prior studies, GCCP was very low; a significant benefit of almost 10% improved prevention of CINV was observed with GCCP. As per MASCC/ESMO guidelines, such an absolute difference should be practice changing. Comprehensive multifaceted strategies are needed to achieve better adherence to antiemetic guidelines.

Abstract P2-12-07: Fdg PET/CT early response prediction for triple negative breast cancer neoadjuvant chemotherapy with addition of carboplatin

Abstract Introduction. The addition of carboplatin to standard neoadjuvant chemotherapy (NAC) including dose-dense (dd) anthracycline-cyclophosphamide (AC) combination followed by taxanes in triple negative breast cancer (TNBC) is the most intense routinely used approach, not widely accepted and potentially of increased toxicity. Fluorodeoxyglucose PET/CT ealy response assessment may aid to decide about treatment intensification. The aim of our study was to define the optimal cut-off of SUVmax decrease for pathological complete response (pCR) prediction after one cycle of AC regimen, in patients who received further AC and taxane plus carboplatin. Material and Methods. 122 patients with TNBC were enrolled into neoadjuvant chemotherapy (NAC) within STRATEGMED 2/267398/4/NCBR/2015 research project in our center between Jan 2018 and Dec 2020, upon approval of Ethics Commitee. Among them 15 patients still continued neoadjuvant treatment at the time of data cut-off, 3 patients did not receive anthracyclines because of lifetime cumulative dose with previous treatments, in 2 patients treatment was interrupted during first cycles of anthracycline-based treatment and in one patient there was no evident (18)F-fluorodeoxyglucose uptake. Remaining 101 patients were enrolled into this study. Baseline PET/CT study before NAC was performed in all patients, 73 patients had baseline PET/CT as well as additional study performed after 1st cycle of chemotherapy. Majority of patients received ddAC followed by docetaxel plus every-three-week carboplatin or weekly paclitaxel plus weekly carboplatin. Patients with residual disease received 8 cycles of capecitabine treatment adjuvantly. Radiation therapy was performed according to guidelines, concurrently or before capecitabine treatment. Mann-Whitney U test was used to assess differences in variables, predictive value was evaluated by receiver-operating characteristic (ROC) curve analysis. Results. 54 patients (53,5%) achieved pCR after neoadjuvant chemotherapy. At baseline, median of SUVmax in breast was 10.2 (IQR 7.2-14.4), whereas median of SUVmax in lymph nodes was 3.7 (IQR 0-10.0). In 16 patients (16%) baseline SUVmax in lymph nodes was higher than in breast (ratio&amp;gt;1). Higher baseline value of SUVmax was associated with pCR achievement (p=0.037). Median SUVmax decrease in breast after one cycle of chemotherapy was 33% (IQR 11%-52%) and was predictive for pCR (p=0.000021). Median decrease of 18-FDG uptake in lymph nodes was more pronounced than in breast (53%; IQR 29%-84%) and was also associated with pCR achievement (p=0.012). For pCR prediction SUVmax decrease cut-off of 40% provided optimal trade-off between sensitivity and specificity, with positive likelihood ratio 2.35, negative likelihood ratio 0.33, positive predictive value 80% and negative predictive value 64%. By ROC analysis, AUC for the prediction of pCR was 0.7604 (p=0.036). Conclusions. While high decrease of SUVmax relatively strongly indicates high pCR chance in TNBC neoadjuvant chemotherapy, lower decrease does not preclude pCR occurrence when intensive four-drug sequential regimen with carboplatin is used. Studies assessing response in reverse sequence chemotherapy with carboplatin are warranted. The study was supported by the Polish National Center of Research and Development MILESTONE project - Molecular diagnostics and imaging in individualized therapy for breast, thyroid and prostate cancer, grant no. STRATEGMED 2/267398/4/NCBR/2015. Citation Format: Marcin Kubeczko, Anna Michalik, Agnieszka Badora-Rybicka, Anna Polakiewicz-Gilowska, Andrea d'Amico, Michał Kalemba, Aleksandra Leśniak, Katarzyna Świderska, Marta Mianowska-Malec, Agnieszka Pasierbek, Barbara Łanoszka, Konstanty Chomik, Barbara Bobek-Billewicz, Michał Jarząb. Fdg PET/CT early response prediction for triple negative breast cancer neoadjuvant chemotherapy with addition of carboplatin [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-07.

1672P Single-dose NEPA versus 3-day aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with risk factors receiving moderately emetogenic chemotherapy (MEC)

In this first head-to-head neurokinin (NK) 1 receptor antagonist (RA) comparative study in patients receiving anthracycline cyclophosphamide (AC) and non-AC MEC, a single dose of NEPA (fixed combination NK1RA, netupitant, and 5-HT3RA, palonosetron) was non-inferior to a 3-day aprepitant (APR) regimen in preventing CINV. The overall (0-120 h) complete response (CR; no emesis, no rescue) rates were 65% NEPA vs 54% APR. While chemotherapy emetogenicity may be the primary consideration when choosing antiemetics, it is established that patient factors also play a role in determining emetic risk.

A Pragmatic Study Evaluating NEPA Versus Aprepitant for Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy.

BackgroundNeurokinin (NK) 1 receptor antagonists (RAs), administered in combination with a 5‐hydroxytryptamine‐3 (5‐HT3) RA and dexamethasone (DEX), have demonstrated clear improvements in chemotherapy‐induced nausea and vomiting (CINV) prevention over a 5‐HT3RA plus DEX. However, studies comparing the NK1RAs in the class are lacking. A fixed combination of a highly selective NK1RA, netupitant, and the 5‐HT3RA, palonosetron (NEPA), simultaneously targets two critical antiemetic pathways, thereby offering a simple convenient antiemetic with long‐lasting protection from CINV. This study is the first head‐to‐head NK1RA comparative study in patients receiving anthracycline cyclophosphamide (AC) and non‐AC moderately emetogenic chemotherapy (MEC).Materials and MethodsThis was a pragmatic, multicenter, randomized, single‐cycle, open‐label, prospective study designed to demonstrate noninferiority of single‐dose NEPA to a 3‐day aprepitant regimen in preventing CINV in chemotherapy‐naive patients receiving AC/non‐AC MEC in a real‐life setting. The primary efficacy endpoint was complete response (no emesis/no rescue) during the overall (0–120 hour) phase. Noninferiority was achieved if the lower limit of the 95% confidence interval (CI) of the difference between NEPA and the aprepitant group was greater than the noninferiority margin set at −10%.ResultsNoninferiority of NEPA versus aprepitant was demonstrated (risk difference 9.2%; 95% CI, −2.3% to 20.7%); the overall complete response rate was numerically higher for NEPA (64.9%) than aprepitant (54.1%). Secondary endpoints also revealed numerically higher rates for NEPA than aprepitant.ConclusionThis pragmatic study in patients with cancer receiving AC and non‐AC MEC revealed that a single dose of oral NEPA plus DEX was at least as effective as a 3‐day aprepitant regimen, with indication of a potential efficacy benefit for NEPA.Implications for PracticeIn the absence of comparative neurokinin 1 (NK1) receptor antagonist (RA) studies, guideline committees and clinicians consider NK1RA agents to be interchangeable and equivalent. This is the first head‐to‐head study comparing one NK1RA (oral netupitant/palonosetron [NEPA]) versus another (aprepitant) in patients receiving anthracycline cyclophosphamide (AC) and non‐AC moderately emetogenic chemotherapy. Noninferiority of NEPA versus the aprepitant regimen was demonstrated; the overall complete response (no emesis and no rescue use) rate was numerically higher for NEPA (65%) than aprepitant (54%). As a single‐dose combination antiemetic, NEPA not only simplifies dosing but may offer a potential efficacy benefit over the current standard‐of‐care.

Machine learning classification of texture features of MRI breast tumor and peri-tumor of combined pre- and early treatment predicts pathologic complete response

PurposeThis study used machine learning classification of texture features from MRI of breast tumor and peri-tumor at multiple treatment time points in conjunction with molecular subtypes to predict eventual pathological complete response (PCR) to neoadjuvant chemotherapy.Materials and methodThis study employed a subset of patients (N = 166) with PCR data from the I-SPY-1 TRIAL (2002–2006). This cohort consisted of patients with stage 2 or 3 breast cancer that underwent anthracycline–cyclophosphamide and taxane treatment. Magnetic resonance imaging (MRI) was acquired pre-neoadjuvant chemotherapy, early, and mid-treatment. Texture features were extracted from post-contrast-enhanced MRI, pre- and post-contrast subtraction images, and with morphological dilation to include peri-tumoral tissue. Molecular subtypes and Ki67 were also included in the prediction model. Performance of classification models used the receiver operating characteristics curve analysis including area under the curve (AUC). Statistical analysis was done using unpaired two-tailed t-tests.ResultsMolecular subtypes alone yielded moderate prediction performance of PCR (AUC = 0.82, p = 0.07). Pre-, early, and mid-treatment data alone yielded moderate performance (AUC = 0.88, 0.72, and 0.78, p = 0.03, 0.13, 0.44, respectively). The combined pre- and early treatment data markedly improved performance (AUC = 0.96, p = 0.0003). Addition of molecular subtypes improved performance slightly for individual time points but substantially for the combined pre- and early treatment (AUC = 0.98, p = 0.0003). The optimal morphological dilation was 3–5 pixels. Subtraction of post- and pre-contrast MRI further improved performance (AUC = 0.98, p = 0.00003). Finally, among the machine-learning algorithms evaluated, the RUSBoosted Tree machine-learning method yielded the highest performance.ConclusionAI-classification of texture features from MRI of breast tumor at multiple treatment time points accurately predicts eventual PCR. Longitudinal changes in texture features and peri-tumoral features further improve PCR prediction performance. Accurate assessment of treatment efficacy early on could minimize unnecessary toxic chemotherapy and enable mid-treatment modification for patients to achieve better clinical outcomes.

Quality of Life Effects of an Oral Fixed Combination of Netupitant and Palonosetron in Chemotherapy-Induced Nausea and Vomiting Prevention: Real-World Evidence in Patients with Breast Cancer Receiving Anthracycline-Cyclophosphamide-Based Chemotherapy

Introduction: In a prospective non-interventional study involving 2,173 patients, we showed that use of the oral fixed combination of netupitant 300 mg and palonosetron 0.5 mg (NEPA) for prevention of chemotherapy (Ctx)-induced nausea and vomiting has beneficial effects on the quality of life (QoL) of patients with various types of cancers receiving highly or moderately emetogenic Ctx. Here, we report on the effects on QoL, effectiveness, and tolerability of NEPA in patients with breast cancer exposed to anthracycline-cyclophosphamide (AC)-based Ctx. Methods: This is a post hoc subanalysis of a prospective non-interventional study in 1,197 patients with breast cancer receiving up to 3 cycles of doxorubicin or epirubicin plus cyclophosphamide and NEPA. NEPA administration was per the summary of product characteristics. Results: In cycle 1 of Ctx, a large proportion of patients (84%) reported “no impact on daily life” (NIDL) due to vomiting; 53% of patients reported NIDL due to nausea. The complete response rate was 86/88/81% in the acute/delayed/overall phase in cycle 1, and NEPA was well tolerated throughout the study. Conclusion: The real-world beneficial effects of NEPA prophylaxis on QoL were confirmed for patients with breast cancer receiving AC. NEPA was effective with a good safety profile in this patient population in clinical practice.

Practice Patterns for Prevention of Chemotherapy-Induced Nausea and Vomiting and Antiemetic Guideline Adherence Based on Real-World Prescribing Data.

Guideline-recommended antiemetic prophylaxis improves nausea and vomiting control in most patients undergoing chemotherapy. Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology (MASCC/ESMO) antiemetic guidelines recommend prophylaxis with a neurokinin-1 receptor antagonist (NK1 RA), a 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), and dexamethasone for patients receiving highly emetogenic chemotherapy (HEC), including anthracycline-cyclophosphamide (AC)- and carboplatin (considered moderately emetogenic chemotherapy)-based chemotherapy. Here, we analyze the use of NK1 RA-5-HT3 RA-dexamethasone for antiemetic prophylaxis associated with HEC and carboplatin. The data source was the Global Oncology Monitor (Ipsos Healthcare). Geographically representative physicians from France, Germany, Italy, Spain, and the U.K. were screened for treatment involvement and number of patients treated per month. Patients' data from January to December 2018 were collected from medical charts and extrapolated on the basis of the total number of physicians who prescribe chemotherapy. The emetic risk of chemotherapy was classified per MASCC/ESMO guidelines. Data from 45,324 chemotherapy-treated patients were collected, representing a total extrapolated prevalence of 1,394,848 chemotherapy treatments included in the analysis. NK1 RAs were used in 45%, 42%, and 19% of patients receiving cisplatin-, AC-, and carboplatin-based chemotherapy, respectively; 18%, 24%, and 7% received the guideline-recommended NK1 RA-5-HT3 RA-dexamethasone combination; no antiemetics were prescribed for 12% of the treatments. Often, physicians' perception of the emetic risk of chemotherapy did not follow MASCC/ESMO guideline classification. Low adherence to antiemetic guidelines was revealed in clinical practice in five European countries, with 15% of all HEC-/carboplatin-based treatments receiving guideline-recommended NK1 RA-5-HT3 RA-dexamethasone prophylaxis and 12% of them receiving no antiemetics. New strategies for improving guideline adherence are urgently needed. Despite recent advances in antiemetic therapy, a substantial proportion of patients experience nausea and vomiting associated with chemotherapy in daily clinical practice. Antiemetic guidelines aim at prevention of chemotherapy-induced nausea and vomiting (CINV), and guideline-consistent antiemetic therapy can effectively prevent vomiting and, to a lesser extent, nausea in most patients with cancer. This study reports low adherence to antiemetic guidelines in the highly emetogenic chemotherapy setting in daily clinical practice across five European countries. Opportunity exists to increase adherence to antiemetic guideline recommendations. Implementation of strategies to facilitate guideline adherence can potentially improve CINV control.

Abstract PS9-61: Incidence of intravenous (IV) hydration post anthracycline-cyclophosphamide (AC) chemotherapy in breast cancer patients

Abstract Background: Managing delayed chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy (HEC) is an unmet need. AC-based HEC is often administered to breast cancer patients. The National Comprehensive Cancer Network and American Society of Clinical Oncology antiemetic guidelines recommend that if breakthrough CINV occurs, treatment should include an antiemetic agent from a different class not used in prophylaxis, as well as intravenous hydration and/or dexamethasone. The primary objective of this study is to retrospectively determine the incidence of IV hydration in post AC chemotherapy in breast cancer patients. Methods: The charts of 270 breast cancer patients receiving AC chemotherapy at University of Alabama at Birmingham (UAB) and on initial 3-drug prophylactic antiemetic regimens were retrospectively reviewed to determine the frequency, incidence, and timing of IV hydration. The hydration incidence was determined for 4 consecutive cycles of AC chemotherapy. The need for hydration was recorded post chemotherapy (e.g., nausea, vomiting, anorexia, loss of appetite, decreased oral intake). Physician and nurse chart notes were reviewed, including documented hydration visits post AC chemotherapy to outpatient infusion areas, local hospital emergency departments, or local hospital inpatient admissions. This report focuses on the patients who were on a guideline-recommended 3-drug regimen (palonosetron [Palo] + Neurokinin-1 [NK1] + dexamethasone [Dex], or ondansetron [Ond] + NK1 + Dex). These patients were followed and monitored for 4 consecutive cycles of AC chemotherapy, and the incidence of hydrations in different cycles was evaluated. Results: 270 patients were included in this analysis; 179 patients received Palo + NK1 + Dex (Group 1) and 91 patients received Ond + NK1 + Dex (Group 2) antiemetic regimens. Of the 179 patients in Group 1, 28 (16%) received hydration post chemotherapy, and 20 (22%) of the 91 patients in Group 2 received hydration (P=0.198, Chi-square test). Demographics and clinical characteristics of the 48 patients receiving hydration are presented in the Table. 28 patients in Group 1 had a total of 36 hydrations, the majority (20 [56%]) of which were in Cycle 1. 26/28 patients received rescue antiemetic treatment at the time of hydration, and 11 had a change in their prophylactic antiemetic regimen after hydration in subsequent chemotherapy cycles. Similarly, in Group 2, 20 patients had a total of 25 hydrations, with the majority (13 [52%]) in Cycle 1. 19 patients received rescue antiemetic treatment at the time of hydration, and 10 had a change in their prophylactic antiemetic regimen in subsequent chemotherapy cycles. Conclusions: The incidence of IV hydration post chemotherapy in breast cancer patients following AC-based HEC regimens occurred predominantly in the first cycle. Unscheduled hydrations, which occur when patients require evaluation in the clinic, and/or emergency department, may be complementary events for breakthrough measurement in CINV and could serve as a surrogate of associated healthcare utilization costs. Further clinical trials may consider evaluating unscheduled hydrations rates as part of a composite complete response endpoint (no breakthrough, no rescue medication, no unscheduled hydration). Table: Demographic and Antiemetic Regimens for Patients Requiring Post-chemo HydrationGroup 1Group 2Palo + NK1 + DexOnd + NK1 + Dex(n=179)(n=91)Post-chemo hydration, n (%)28 (16)20 (22)Demographics and Clinical Characteristics of Patients with Post-chemo Hydration (n=48)Median age, years (range)s56 (35-73)58 (33-70)Sex, n (%)Female27 (96)20 (100)Male1 (4)0ECOG Performance Status, n (%)015 (53)12 (60)112 (43)7 (35)201 (5)Unknown1 (4)0IV access, n (%)Central26 (93)20 (100)Peripheral2 (7)0Antiemetic Regimens Prior to Chemotherapy and Hydration RequirementsTotal number of patients requiring hydration, n (%)28 (16)20 (22)Total number of hydrations, n3625Number of hydrations in Cycle 1, n (%)20 (56)13 (52)Visits, n (%)Office16 (57)12 (60)Emergency department12 (43)8 (40)Rescue antiemetic(s) at time of hydration, n (%)26 (93)19 (95)Prophylactic antiemetic regimen switched, n (%)11 (39)10 (50)Dex = dexamethasone; ECOG = Eastern Cooperative Oncology Group; IV = intravenous;NK1 = Neurokinin-1; Ond = ondansetron; Palo = palonosetron. Citation Format: Rudolph M. Navari, Michael C. Mosier. Incidence of intravenous (IV) hydration post anthracycline-cyclophosphamide (AC) chemotherapy in breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-61.

Abstract PS13-09: Chemotherapy-induced nausea and vomiting (CINV) risk after prior breakthrough CINV: Unmasking the false average

Abstract Background: Although many studies have demonstrated consistent levels of effectiveness of CINV prophylaxis for the entire study population across multiple chemotherapy cycles, rarely have studies reported how each patient’s risk of subsequent CINV differs based on prior cycle breakthrough CINV with the same prophylaxis. We lack data on whether prophylaxis continues to fail in the same group of patients each cycle, or whether failure is random with each subsequent cycle. We sought to evaluate individual patients’ risk of repeat CINV in each subsequent chemotherapy cycle. Methods: In a prospective, 4-cycle CINV prophylaxis trial of oral or intravenous combination netupitant/palonosetron (NEPA) + dexamethasone (day 1) for patients with breast cancer receiving anthracycline + cyclophosphamide (AC), we defined CINV as vomiting or use of rescue medication during days 1-5 after chemotherapy. Patients without CINV were classified as complete response (CR); the rest as treatment failure (TF). We analyzed patients’ sequences of CR and TF, and compared CR or TF for cycles 2-4 based on cycle 1 outcomes, using chi-square statistics. To provide context, we performed a post-hoc similar analysis of results reported by Herrstedt et al [2005] from a clinical trial of ondansetron + aprepitant (APR) for patients with breast cancer receiving 4 cycles of AC. Results: The 402 female patients in the NEPA trial received a total of 1,299 cycles. In cycle 1, 99 (24.6%) patients experienced TF (TF1); over all 4 cycles, TF occurred 253 times (19.5%). Patients with CR in cycle 1 (CR1) had a ≥92% rate of CR in cycle 2; their rates of repeat CR were similar in each subsequent cycle. Patients with TF1 had nearly equal risk of CR or TF in cycle 2 (45:55); thereafter 85% of this TF1 subgroup repeated their cycle 2 outcome (CR or TF) in cycles 3 and 4. Over all cycles of NEPA, patients with CR1 subsequently had CR in &amp;gt;90% of cycles 2-4; those with TF1 subsequently had TF in 49.8% of cycles 2-4 (p&amp;lt;0.0001) (see Table). We separately examined Herrstedt’s evaluation of 433 patients across 1537 cycles with APR. In cycle 1, TF was seen 213 times (49.2%), with TF reported in 46.7% of cycles 1-4. We found that patients with CR1 had an 80.5% rate of CR in cycle 2 and repeat CR rates were higher in subsequent cycles. Patients with TF1 had TF in cycle 2 (TF2) at a rate of 78.4%, with 76.6% TF3 and 72.7% TF4. For APR, CR1 resulted in subsequent CR in 78.6% of cycles 2-4 while patients with TF1 again had TF in 74.8% of cycles 2-4 (p&amp;lt;0.0001). Patients with TF1 were more likely to later drop from the study (see Table). Notably, among those with CR1 after APR, the few patients who later had TF in any cycle, had a subsequent repeat failure rate similar to those with TF1. Conclusions: When patients receiving guideline-recommended triple antiemetic prophylaxis successfully avoided CINV in their first cycle of HEC, they had 80-95% likelihood of repeating that success in later cycles. After NEPA, those whose prophylaxis failed in cycle 1 did not face a similar high risk of repeat failure in cycle 2. The pattern of repeat failure after aprepitant was different, with a high repeat failure risk starting in cycle 2. These findings strongly suggest that consistent population average CR rates reported across cycles may mask a higher repeat failure rate for individual patients that experience cycle 1 CINV, particularly for aprepitant. Further study of this phenomenon is needed for other HEC regimens, and to confirm the lack of high repeat failure seen in cycle 2 for NEPA. Repeat CINV in Later Cycles, Based on Cycle 1 ResultsNEPAAprepitant + OndansetronInitial Cycle Result (n/total initial cycles)CR1 (303/402)TF1 (99/402)CR1 vs TF1 (P value)CR1 (220/433)TF1 (213/433)CR1 vs TF1 (P value)Subsequent CR cycles (n, % of total subseq. cycles)636 (93.0%)107 (50.2%)&amp;lt;0.0001464 (78.6%)124 (25.2%)&amp;lt;0.0001Subsequent TF cycles (n, % of total subseq. cycles)48 (7.0%)106 (49.8%)126 (21.4%)370 (74.8%)Total subsequent cycles (n, % of total subseq. cycles)684 (100%)213 (100%)590 (100%)494 (100%)Dropped vs ITT* (n, % ITT cycles)225 (24.8%)84 (28.3%)0.226370 (10.6%)145 (22.7%)&amp;lt;0.0001* The NEPA trial was closed when the last patient completed the first cycle, resulting in an artificially high proportion of patients that did not complete 4 cycles. Citation Format: Rudolph M Navari, Gary Binder, Alexander Molassiotis, Eric Roeland, Kathryn J. Ruddy, Thomas W. LeBlanc, Dwight D. Kloth, Silvia Sebastiani, Lina Y. Dimberg, Luke M. Schmerold, Xing Liu, Lee Schwartzberg. Chemotherapy-induced nausea and vomiting (CINV) risk after prior breakthrough CINV: Unmasking the false average [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-09.

Abstract PS3-14: Assessment of clip locations on breast MRI during NAC to guide tumor bed biopsy at mid-treatment

Abstract Background: The I-SPY 2 TRIAL randomizes patients with breast cancer to neoadjuvant chemotherapy (NAC) with or without experimental agents followed by anthracycline-cyclophosphamide (AC). As part of a de-escalation strategy to avoid overtreatment in good responders, combined information from serial MRI and mid-treatment core biopsy will be used to identify patients who may be candidates to skip AC. Presented are results of a pilot study to assess the location of biopsy clip in relation to tumor enhancement in MRI before and during treatment. Methods: 40 patients enrolled in I-SPY 2 who underwent mid-treatment core biopsy were reviewed. Patients had MRIs at four time points: pre-treatment (T0), early treatment (T1, 3 weeks after the start of first regimen), inter-regimen (T2, 12 weeks after completing the first regimen), and pre-surgery (T3). Clip visibility and location were assessed by a trained researcher on T1 weighted, fat suppressed dynamic contrast enhanced MR images at three time points: T0, T1, and T2. If clip was visible, location was scored 1 (inside), 2 (edge), or 3 (outside) in relation to tumor enhancement seen on a signal enhancement ratio (SER) map. Clips inside (score 1) were fully embedded and surrounded by a clear margin of tumor enhancement. Clips on the edge (score 2) were not fully embedded, with a portion of the clip touching tumor enhancement. Clips outside (score 3) had no portion of clip touching tumor enhancement. For patients with a focal tumor but with multiple clips visible in MRI, the clip most embedded within tumor enhancement was designated as the primary clip for evaluation. In cases of multifocal disease, the clip visualized in the largest area of tumor enhancement was assessed. Clips touching tumor cavity edge and enhancement were scored as 3. Results: Among 40 patients, two patients had no clips visualized in MRI at all three time points. One patient had no clip visualized at T0, but a clip was observed at T1 and T2. In addition, one T1 MRI was rejected due to incomplete exam and one T2 MRI was rejected due to different scanner from baseline. At T0, 51% (19/37) of clips were inside tumor enhancement and no clips were assessed outside tumor enhancement. 59% (22/37) of clips at T1 were on the edge or outside. At T2, 73% (27/37) of clips were on the edge and 19% (7/37) of clips were outside. While no clips were identified outside of tumor at baseline, tumor shrinkage with treatment resulted in clips outside of tumor in approximately 20 percent of cases at inter-regimen, and higher rates of clips identified at tumor edge. Conclusions: Clips were visible and location could be assessed in MRI in a majority of cases. Clip evaluation can be challenging and attention to clip placement is essential for patients with multifocal disease or diffuse tumors. The results of this study may have implications for assisting the mid-treatment core biopsy and selecting candidates for de-escalation of neoadjuvant chemotherapy. Table 1: Clips observed at three MR time pointsT0T12T231 (inside)191532 (edge)1821273 (outside)01171 No clips were seen outside tumor enhancement 2 One T1 MR was rejected due to incomplete exam 3 One T2 MR was rejected due to different scanner from baseline Citation Format: Teffany Joy Bareng, Jessica Gibbs, Wen Li, Natsuko Onishi, Bonnie N Joe, Elissa Price, Barbara LeStage, Coleen Crespo, I-SPY 2 Imaging Working Group, I-SPY 2 Consortium, Nola M Hylton. Assessment of clip locations on breast MRI during NAC to guide tumor bed biopsy at mid-treatment [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-14.

Abstract PS13-35: Evaluation of age as a risk factor for CINV in breast cancer patients: Post-hoc analysis of the German real-world AkyPRO study

Abstract Background: The primary objective of the prospective, non-interventional study (NIS) AkyPRO was the evaluation of quality of life (QoL) in adult cancer patients (pts) receiving NEPA as antiemetic prophylaxis. Secondary endpoints were efficacy and safety of NEPA. NEPA is administered as an oral fixed dose combination of 300 mg of the neurokinin-1-receptor antagonist - (NK1RA) netupitant and 0,5 mg of the 5-hydroxytryptamin-3-receptor antagonist (5-HT3RA) palonosetron once per chemotherapy cycle as primary prophylaxis for chemotherapy-induced nausea and vomiting (CINV) associated with moderately (MEC) or highly (HEC) emetogenic chemotherapy. In modern antiemetic guidelines, anthracycline/ cyclophosphamide (AC) - containing chemotherapy (AC-CT) is classified as HEC requiring triple antiemetic prophylaxis with a 5-HT3RA, a NK1RA and dexamethasone. Pts with breast cancer (BC) have additional risk factors for nausea and vomiting, like female sex and younger age, thus representing a high-risk group for CINV. Here, we present a post-hoc analysis of quality of life data and effectiveness of NEPA in the subgroup of BC pts in two age groups ≥ and &amp;lt; 60 years (y), who were treated with AC-CT in the AkyPRO NIS. Methods: The AkyPRO NIS has been conducted to evaluate quality of life and effectiveness of antiemetic prophylaxis with NEPA in cancer pts with various cancer entities receiving single day or two day MEC or HEC in a real life situation. Quality of life (QoL) was recorded by FLIE questionnaires. Effectiveness of NEPA as indicated by complete response (CR: no vomiting, no rescue medication), additional medication, and adverse events were recorded in patient diaries over three consecutive chemotherapy cycles. Patients and physicians documented overall antiemetic control on a 4-point scale (very good, good, satisfactory, poor). Results: In total, the AkyPro NIS enrolled 2,427 pts. 1,428 pts (65.7 %) had breast cancer. In this post hoc analysis 1,197 BC pts receiving AC-CT (83 % of all BC pts) were evaluated. 782 pts (65%) were &amp;lt;60y, 415 (35%) ≥ 60y old. Most pts received AC-CT in the adjuvant or neoadjuvant setting. Pts ≥ 60y reported a higher CR rate in the overall phase over 3 cycles (c1 88%, c2 90%, c3 88%) than pts &amp;lt;60y (c1 78%, c2, 78%, c77%). Pts ≥ 60y also experienced moderate or severe nausea less frequently, with the non-significant nausea (NSN) rate being 67, 67, 70% c1-c3 in these pts vs. 57, 59, 58% in c1-c3 in younger pts. QoL data confirmed this observation. Older pts reported more often to have no impact on daily life (NIDL) due to nausea (58-62% in c1-c3) than younger pts (50-54% in c1-c3). Comparison of patients’ and physicians’ perception of antiemetic treatment effectiveness revealed that in both groups the majority estimated the effectiveness of antiemetic prophylaxis with NEPA high and comparably well and good or very good. Conclusion: This real-life study confirmed the effectiveness of NEPA in preventing CINV in the subgroup of BC pts receiving AC-chemotherapy. Pts ≥ 60y experienced less CINV compared to pts &amp;lt;60y, confirming that younger age represents a risk factor for CINV and indicating that the choice of an adequate antiemetic prophylaxis is crucial in this group of pts. Citation Format: Joerg Schilling, Steffi Busch, Martin Hollaender, Gabriele Kaltenecker, Eberhard Müller, Thomas Resch, Angelika Till, Meinholf Karthaus. Evaluation of age as a risk factor for CINV in breast cancer patients: Post-hoc analysis of the German real-world AkyPRO study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-35.

Efficacy of intravenous NEPA, a fixed NK1/5-HT3 receptor antagonist combination, for the prevention of chemotherapy-induced nausea and vomiting (CINV) during cisplatin- and anthracycline cyclophosphamide (AC)-based chemotherapy: A review of phase 3 studies.

This paper presents an overview of the efficacy of intravenous (IV) NEPA (fixed combination of the NK1RA, fosnetupitant, and 5-HT3RA, palonosetron) relative to oral NEPA and also to historical data for other NK1RA regimens. Data is compiled from 5 pivotal NEPA studies in adult chemotherapy-naïve patients with solid tumors undergoing either cisplatin- or anthracycline cyclophosphamide (AC)-based chemotherapy. Additionally, data was reviewed from 10 pivotal Phase 3 studies utilizing other NK1RA regimens approved for clinical use. The overall (0-120 h) complete response (no emesis, no rescue use), no emesis, and no significant nausea rates for IV NEPA were similar to that of oral NEPA and were consistently numerically higher than historical NK1RA regimens. As a single-dose prophylactic antiemetic combination given with dexamethasone, IV NEPA is a highly effective and convenient guideline-compliant antiemetic agent which may offer a safety benefit over other IV NK1RA regimens due to its lack of associated hypersensitivity and injection-site reactions.

Analysis of Quality-of-Life (QoL) in Patients Receiving NEPA for Prevention of Chemotherapy-Induced Nausea (CINV) and Vomiting

Introduction: Chemotherapy-induced nausea and vomiting (CINV) is a common and distressing side effect that has a detrimental impact on QoL. For pts receiving highly emetogenic chemotherapy (HEC), which includes those on anthracycline-cyclophosphamide (AC)-based regimens, a triple combination of a neurokinin-1 receptor antagonist (NK1 RA), a 5-hydroxytryptamine-3 (5-HT3) RA and dexamethasone is recommended by the NCCN and MASCC/ESMO. The complexity of the NK1 RA-based schedules may be a reason for the low adherence to antiemetic guidelines and a not sufficient control of CINV in pts receiving HEC and MEC. NEPA is the only available fixed-combination antiemetic. It is composed of an NK1 RA, netupitant (300 mg) and a 5-HT3 RA, palonosetron (0.50 mg); thus, it acts by blocking two main emetic pathways in a single dose and eases compliance to guidelines. Methods: Prospective, non-interventional study at 162 sites in Germany from 09/2015 to 03/2018. The aim was to determine QoL of adult cancer pts receiving NEPA for the prevention of nausea and vomiting associated with 1 or 2 day HEC or MEC in daily clinical practice. The primary outcome was measured via the Functional Living Index-Emesis (FLIE) questionnaire. FLIE questionnaires were analyzed according to the FLIE scoring and administration manual v12; higher scores correlated to better performance on daily life activities due to the lower occurrence of nausea and vomiting. 'No impact on daily life (NIDL) activities' for individual nausea and vomiting domains was defined as a FLIE score higher than 53.8; NIDL for the combined domains of nausea and vomiting was defined as a FLIE score higher than 108. Secondary objectives included evaluating effectiveness, as determined by measuring the rate of complete response (CR) and rescue medication, as well as safety outcomes. Efficacy was documented by the treating physicians and via patient diaries for 3 Ctx cycles within 24 hrs and on 4 additional d after Ctx. Safety, additional medication and physicians' overall satisfaction was reported via eCRF. Results: A total of 2429 pts were enrolled, 2405 of whom were assessed for eligibility; of these, 2173 were included in the final analysis and constitute the full analysis set population (FAS). Evaluable FLIE questionnaires were collected from 1886 (88%) pts in cycle 1, 1795 (88%) pts in cycle 2 and 1698 (86%) pts in cycle 3. A total of 1389 pts received HEC and 764 MEC in cycle 1. The majority of pts (91%) were scheduled to receive 1-day ctx at study entry. More than half of the pts (1230, 56%) received anthracycline/cyclophosphamide-(AC), 19% carboplatin-, 8% cisplatin-, 7% oxaliplatin- and 9% other CTs. NIDL due to vomiting during cycle 1 was reported by 84% of pts in the HEC group and 82% in the MEC group. These frequencies were maintained in cycles 2 and 3. NIDL due to nausea increased from 54% in cycle 1 to 58% in cycle 3 for pts receiving HEC, and from 59% in cycle 1 to 66% in cycle 3 for pts in the MEC group. The rates for the combined domain of NIDL due to nausea and vomiting were consistent across cycle 1 (64%) and in cycles 2 and 3 (66% in each cycle) for pts in the HEC group, while the rates increased from 67% in cycle 1 to 73 and 74% in cycles 2 and 3, respectively, for pts receiving MEC. The CR rate (no emesis and no use of rescue medication) was 89% in the acute phase (0-24 h), 87% in the delayed phase (25-120 h) and 83% in the overall period (0-120 h) in cycle 1. The no significant nausea (NSN) rate was 79 % in the acute, 75 % in the delayed and 67 % in the overall phase in cycle. The majority of physicians (≥89%) and pts (≥86%) rated the effectiveness of NEPA prophylaxis as 'very good' or 'good' during all three ctx cycles. The most common NEPA-related AEs, which occurred in &amp;gt;1% of pts in the overall study period, were fatigue (3%), constipation (3%), nausea (2%) and insomnia (2%). There were no reports of NEPA-related deaths. Conclusions: Real-life data show that NEPA was effective in the prevention of chemotherapy-induced nausea and vomiting in cancer patients. NEPA had beneficial effects on the quality of life and was highly effective in the acute and delayed phase of HEC and MEC. NEPA antiemetic effectiveness was rated highly both by patients and physicians. Disclosures Karthaus: RIEMSER: Consultancy, Honoraria. Schilling:Riemser: Honoraria.