Epirubicin And Cyclophosphamide Research Articles

EFFICACY AND SAFETY OF A DEXAMETHASONE-BASED MOUTHWASH TO PREVENT CHEMOTHERAPY-INDUCED STOMATITIS IN WOMEN WITH BREAST CANCER: A MULTICENTRE, OPEN-LABEL, RANDOMISED PHASE 2 STUDY.

No standard approach other than oral care is available for preventing chemotherapy-induced stomatitis in patients with breast cancer. In this randomized, controlled phase 2 trial, we aimed to assess the efficacy and safety of a dexamethasone-based mouthwash in preventing chemotherapy-induced stomatitis in patients with early breast cancer. Patients with breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapy were selected and allocated in a 1:1 ratio to the intervention and control groups. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash, whereas the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis. This was a phase 2 study, and the significance level for the analysis of the primary endpoint was set a priori at 0.2. Data pertaining to 58 patients in the control group and 59 patients in the intervention group were analyzed. Stomatitis incidence was 55% and 38% in the control and intervention groups, respectively (risk ratio, 0.68; 80% confidence interval, 0.52-0.88; P = .052). Stomatitis severity was lower in the intervention group than in the control group (P = .03). The proportion of patients who adhered to the mouthwash regimen was 87% (interquartile range, 67.8%-95.3%). No severe oral infections were observed. The dexamethasone-based mouthwash safely reduced stomatitis incidence and severity in patients receiving chemotherapy for early breast cancer. Phase 3 clinical trials are warranted for validating our results.

A Retrospective Study on Previously Untreated Non-metastatic Breast Cancer Patients at a Tertiary Care Hospital

Introduction: The combination of adoxorubicin and cyclophosphamide (AC) followed by a taxane (Docetaxel or Paclitaxel) and epirubicin and cyclophosphamide (EC) followed by a taxane (Docetaxel or Paclitaxel) is a standard regimen for breast cancer patients. In this study, we compared the three-year overall survival (OS) and progression free survival (PFS) of a patient with previously untreated non-metastatic breast cancer patients. Objectives: To find out the overall survival and progression free survival among previously untreated non-metastatic breast cancer patients after standard chemotherapy. Methods: Fifty-six patients received four cycles of doxorubicin at a dose of 60mg/m2 and cyclophosphamide at a dose of 600 mg/m2 followed by four cycles of paclitaxel at a dose of 175mg/m2. Thirteen patients received AC followed by four cycles of docetaxel at a dose of 75mg/m2. Twenty-one patients received four cycles of epirubicin (75mg/m2) and cyclophosphamide (600mg/m2), followed by four cycles of paclitaxel (175mg/m2). Twelve patients were given EC followed by four cycles of docetaxel (75mg/m2). Results: The four groups of patients had similar characteristics. Overall survivalafter three years was 92% in AC followed by paclitaxel, 98% in AC followed by docetaxel, 95% and 97% in EC followed by paclitaxel and docetaxel respectively. One year of PFS in AC followed by paclitaxel and docetaxel was 98% and 100% respectively whereas in EC followed by paclitaxel and docetaxel were 98% and 98% respectively. The four arms had 96%, 98%, 97% and 96% PFS after two years respectively. This research also revealed that four chemotherapy regimens had three-year survival rates of 93%, 98%, 93% and 96% respectively. Conclusion: AC or EC followed by taxane regimens well suitable regimens for the population of patients with previously untreated non-metastatic breast cancer patients. The findings show the need for continued observation as well as taking into account the treatment of other patients throughout different periods. JAFMC Bangladesh. Vol 18, No 2 (December) 2022: 11-14

Nanoparticle albumin-bound paclitaxel-based neoadjuvant regimen: A promising treatment option for HER2-low-positive breast cancer

This study aimed to compare the efficacy of neoadjuvant systemic therapy (NST) with solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel in human epidermal growth factor receptor 2 (HER2)-low-positive and HER2-zero breast cancers. A total of 430 patients receiving 2-weekly dose-dense epirubicin and cyclophosphamide (EC) followed by 2-weekly paclitaxel (Sb-P, Lps-P, or Nab-P), or 3-weekly EC followed by 3-weekly docetaxel for NST were enrolled in the study. In HER2-low-positive patients, the pathological complete response (pCR) rate in Nab-P group was significantly higher than that in the other three paclitaxel groups (2.8 % in Sb-P group, 4.7 % in Lps-P group, 23.2 % in Nab-P group and 3.2 % in docetaxel group, p < 0.001). In HER2-zero patients, the pCR rate did not differ significantly among the four paclitaxel groups (p = 0.278). The NST regimen containing Nab-P could be considered a promising treatment option in HER2-low-positive breast cancer.

Volume change rate before and after neoadjuvant systemic therapy of breast cancer is an efficacious evaluation index to predict pathological complete response.

Neoadjuvant systemic therapy (NST) is widely applied in breast cancer treatment, but individuals respond differently to the same NST regimen. It is unclear which patients should adjust their NST regimen and what such an adjustment should be, especially for patients with radiologically partial response (PR). This study aimed to identify a quantitative efficacy evaluation index to evaluate the therapeutic effect of NST. 164 patients were enrolled in this study received four cycles of epirubicin and cyclophosphamide (EC), followed by four cycles of taxanes with trastuzumab [T(H)], if needed. Of patients with a volume change rate of EC treatment (δV1) below 0.80, more than half benefited from subsequent T(H) treatment compared with EC treatment. Importantly, for δV1 of 0.80 and higher, patients' subsequent T(H) treatment was not as efficient as previous EC treatment and they have a lower pathological complete response (pCR) rate. Across all patients, nanoparticle albumin-bound paclitaxel had a numerically higher pCR rate over other taxanes in patients with triple-negative breast cancer. This study showed that the volume change rate is better than the diameter change rate in monitoring the therapeutic effect of NST. Furthermore, δV1 is a good quantitative efficacy evaluation index to distinguish patients resistant to EC treatment and predict the pCR rate and guide the adjustment of individualized NST regimens.

Neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel plus trastuzumab and pertuzumab followed by epirubicin and cyclophosphamide for operable HER2-positive primary breast cancer: a multicenter phase II clinical trial (PerSeUS-BC04)

BackgroundNanoparticle albumin-bound paclitaxel (nab-PTX) is a promising antibody partner for anti-human epidermal growth factor receptor 2 (HER2). We performed neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer (BC) using nab-PTX plus trastuzumab (T-mab) and pertuzumab (P-mab), followed by epirubicin and cyclophosphamide (EC).MethodsIn this multicenter phase II clinical trial (January 2019–July 2020), patients with stage I (T1c)-IIIB HER2-positive primary BC were treated with four cycles of nab-PTX plus T-mab and P-mab, followed by four cycles of EC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints were clinical response rate (RR), adverse events (AE), and tumor-infiltrating lymphocytes (TILs) in biopsy samples.ResultsIn total, 43 patients were enrolled (mean age, 54 years). Twenty-two patients had HER2, and 21 patients had luminal/HER2-subtypes. The overall pCR rate was 53.5% (23/43, 95% CI: 42.6–64.1%, p = 0.184), whilst the pCR for HER2 was 68.2% (15/22, 95% CI: 45.1–86.1) and 38.1% for luminal/HER2 (8/21, 95% CI: 18.1–61.6%). The RR was 100% [clinical (c) CR:25, partial response (PR): 18]. AEs (≥ G3) included neutropenia (23.3%), leukopenia (7.0%), liver dysfunction (7.0%), and peripheral neuropathy (4.7%) when nab-PTX was administered. EC administration resulted in leukopenia (34.2%), neutropenia (31.6%), and febrile neutropenia (15.8%). The TILs in preoperative biopsy samples were significantly higher in pCR compared to non-pCR samples.ConclusionNab-PTX plus T-mab and P-mab induced a high pCR rate in HER2-positive BC, particularly in the HER2-subtype. Given that AEs are acceptable, this regimen is safe and acceptable as NAC for HER2-positive BC.

The Comparative Safety of Epirubicin and Cyclophosphamide versus Docetaxel and Cyclophosphamide in Lymph Node-Negative, HR-Positive, HER2-Negative Breast Cancer (ELEGANT): A Randomized Trial.

Simple SummaryAnthracycline and taxane-based chemotherapy are the cornerstone of adjuvant therapy for early breast cancer. In recent years, several trials explored the efficacy of the anthracycline-free regimens, especially for HER2-negative breast cancer patients, which turned out to be a feasible alternative. However, there is no comparison between epirubicin and cyclophosphamide versus docetaxel and cyclophosphamide about their safety and efficacy to date. ELEGANT is the first phase III randomized trial comparing the safety and efficacy of EC versus TC, and it reports comprehensive safety profiles of both regimens with a primary endpoint of grade 3 to 4 neutropenia rate.Background: In adjuvant settings, epirubicin and cyclophosphamide (EC) and docetaxel and cyclophosphamide (TC) are both optional chemotherapy regimens for lymph node-negative, hormone receptor (HR)-positive, human epidermal receptor 2 (HER2)-negative breast cancer patients. Neutropenia is one of the most common adverse events (AEs) of these regimens. The rate of grade 3–4 neutropenia varies in different studies, and direct comparisons of safety profiles between EC and TC are lacking. Method: ELEGANT (NCT02549677) is a prospective, randomized, open-label, noninferior hematological safety trial. Eligible patients with lymph node-negative HR+/HER2-tumors (1:1) were randomly assigned to received four cycles of EC (90/600 mg/m2) or TC (75/600 mg/m2) every three weeks as adjuvant chemotherapy. The primary endpoint was the incidence of grade 3 or 4 neutropenia defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 on an intention-to-treat basis. Noninferiority was defined as an upper 95% CI less than a noninferiority margin of 15%. Results: In the intention-to-treat population, 140 and 135 patients were randomized into the EC and TC arms, respectively. For the primary endpoint, the rate of grade 3 or 4 neutropenia is 50.71% (95% CI: 42.18%, 59.21%) in the EC arm and 48.15% (95% CI: 39.53%, 56.87%) in the TC arm (95%CI risk difference: −0.100, 0.151), showing the noninferiority of the EC arm. For secondary endpoints, the rate of all-grade anemia is higher in the EC arm (EC 42.86% versus TC 22.96%, p = 0.0007), and more patients suffer from nausea/vomiting, hair loss, and nail changes (p < 0.01) in the EC arm. No statistically different disease-free survival was observed between the two arms (p = 0.13). Conclusion: EC is not inferior to TC in the rate of grade 3 or 4 neutropenia, but more other AEs were observed in the EC group.

Efficacy and safety of dexamethasone-based mouthwash to prevent chemotherapy-induced stomatitis in women with breast cancer: A multicenter, open-label, randomized phase II study.

12103 Background: Stomatitis, a frequent adverse event in patients undergoing chemotherapy, can lead to pain, ulcers, bleeding, and malnutrition due to reduced oral intake, which not only deteriorates quality of life but may also result in dose reduction or interruption of chemotherapy. However, there is currently no standard approach for preventing chemotherapy-induced stomatitis. Therefore, this study aimed to assess the efficacy and safety of a dexamethasone-based mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer. Methods: We conducted a multicenter, randomized, controlled phase II trial. Patients with early-stage breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapies were allocated in a 1:1 ratio to the intervention and control groups. The sample size was set to 120 cases based on the following assumptions: stomatitis incidence of 50% in the control group and 30% in the intervention group, alpha error of 0.2, one-sided power of 0.9, and dropout proportion of 10%. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash (10 mL, 0.1 mg/mL; swish for 2 min and spit, 4 times daily for 9 weeks), and the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis that was compared between the two groups. Results: There were 60 patients in the control group and 61 in the intervention group. One patient in the control group and two in the study group withdrew consent; one patient in the control group was excluded because of discontinuation of the first cycle of chemotherapy and unavailability of data related to the incidence of stomatitis. Finally, the data of 58 patients in the control group and 59 in the intervention group were analyzed. There were no differences in age and chemotherapy regimens between the groups. The incidence of stomatitis was 55% in the control group and 38% in the intervention group (risk ratio 0.68; 80% confidence interval, 0.52 – 0.88; p = 0.052). The grade of stomatitis (0/1/2/3) was significantly lower in the study group (intervention group vs. control group: 37/13/7/2 vs. 26/16/7/9, p = 0.03). There were no differences in the duration of stomatitis between the groups. Moreover, the percentage of patients who adhered to the mouthwash regimen was 87% (range, 14% – 100%). There were no significant differences in the occurrence of other adverse events between the groups, and only one case of oral candidiasis was observed in the intervention group. Conclusions: Dexamethasone-based mouthwash safely reduced the incidence and severity of stomatitis in patients receiving chemotherapy (EC/TC) for early breast cancer. Clinical trial information: UMIN000030489.

Use of Dose-dense EC Chemotherapy in Early Breast Cancer – Experience from Two London Hospitals

Purpose: Dose-dense (dd) chemotherapy regimens reduce breast cancer recurrence and mortality with no significant increase in non-cancer related mortality [1]. However, uptake is poor, probably due to concerns regarding toxicity. We aimed to quantify rates of toxicity and dose reduction in patients receiving dd epirubicin and cyclophosphamide (EC), and to identify any associated patient factors.

198P Complications associated with prolonged GCSF with dose-dense EC chemotherapy for early breast cancer patients

Primary granulocyte-colony stimulating factor (GSCF) prophylaxis with dose-dense chemotherapy for early stage breast cancer is routine practice to prevent febrile neutropenia (FN). Our current practice administers 7 days of GCSF, which reduces the FN risk but is associated with extra toxicity and costs. We reviewed the rates of FN, neutropenia, hospital admissions and GCSF-related toxicity in early stage breast cancer patients receiving 7 days of GCSF with dose-dense epirubicin and cyclophosphamide (EC).

Interstitial lung disease associated with adjuvant and neoadjuvant chemotherapy in early breast cancer

BackgroundInterstitial lung disease (ILD) is a rare adverse event in patients receiving adjuvant or neoadjuvant chemotherapy (NAC) for breast cancer. Few studies have reported the frequency of ILD in detail, and only small numbers of cases have been described in the literature.Given these previous findings concerning ILD, we retrospectively examined the clinicopathological characteristics of five cases of ILD who had received epirubicin and cyclophosphamide (EC) and compared their findings with non-ILD cases.MethodsThe present single-center retrospective study included breast cancer patients who underwent adjuvant chemotherapy or NAC at our hospital between January 2014 and January 2021.ResultsThirty-nine patients who had received EC for operable breast cancer were enrolled in this study. ILD developed 5 out of 39 patients (12.8%). The incidence of ILD in patients with non-dose-dense (dd) or dd chemotherapy was statistically significantly different (p = 0.0149). ILD occurred in three patients during dd EC treatment and two during weekly paclitaxel (wPTX) after dd EC. ILD was detected in one patient with high Krebs von den Lungen-6 (KL-6) levels, in two patients with continuous pyrexia, and in two patients from computed tomography imaging, which was taken to estimate the efficacy of chemotherapy, in two patients. Three of the 5 ILD patients underwent bronchoalveolar lavage, and 2 of these patients were diagnosed with Pneumocystis jirovecii pneumonia (PCP). There were no cases of serious ILD that required steroid pulse therapy.ConclusionsDd chemotherapy may be associated with an increased ILD frequency, which may reflect developing PCP. Careful monitoring and a timely diagnosis are useful for detecting early-stage ILD.

Differential effect on different immune subsets of neoadjuvant chemotherapy in patients with TNBC

BackgroundTriple-negative breast cancer (TNBC) is the most aggressive form of breast cancer (BC). Due to the absence of targets such as HER2 or hormone receptors, early TNBC is treated with...

Complete atrioventricular block and torsade de pointes due to dose-dense epirubicin and cyclophosphamide therapy.

The dose-dense epirubicin and cyclophosphamide (EC) therapy for breast cancer decreases the risk of cancer recurrence and death. However, epirubicin and cyclophosphamide also cause cardiotoxicity, and cardiomyopathy is the most well-known related adverse effect. A 58-year-old woman presented to our hospital with palpitations 2weeks after her final dose-dense EC therapy for breast cancer. Holter electrocardiogram (ECG) showed transitory complete atrioventricular block (CAVB) and torsade de pointes. A 12-lead ECG showed QT prolongation in addition to CAVB. Patients receiving dose-dense EC therapy should be monitored more carefully with ECG due to their risk of fatal arrhythmias.

Taste alterations in patients with breast cancer following chemotherapy: a cohort study.

Chemotherapy-induced taste and smell alterations in cancer patients are associated with multiple adverse effects, namely, malnutrition, weight loss, and a diminished quality of life. The aim of this prospective study was to identify the incidence of taste alterations following epirubicin and cyclophosphamide (EC) chemotherapy in patients with breast cancer without previous history of cancer or chemotherapy. Forty-one patients undergoing EC chemotherapy for breast cancer at Tokai University Hospital were included. A subjective (questionnaire) and an objective (filter paper disk method) assessment for 5 basic tastes were administered on day 4 post-chemotherapy and immediately before the subsequent cycle of chemotherapy for each cycle, in addition to an olfactory evaluation and oral examination. The correlation between subjective and objective taste alterations and factors influencing these alterations were analyzed by statistical means. The mean incidence of subjective taste alteration on the 4th day after chemotherapy was 53%. In each of the 4 cycles, taste alterations decreased to about 9.0% immediately before the next cycle. A significant correlation between subjective and objective assessments was seen only for salty taste, suggesting important differences in subjective versus objective assessment outcomes. A multivariate analysis indicated that age and body surface area influenced taste alterations. EC chemotherapy induced taste alterations in more than 50% of patients, which decreased to less than 10% immediately before the next chemotherapy cycle. A combination of objective and subjective assessments is essential to evaluate taste alterations induced by EC chemotherapy. These could be used in routine clinical practice.

Abstract P1-10-05: Evaluation of germline whole exome sequencing of early breast cancer patients with triple negative breast cancer (TNBC) included in a prospective study of neoadjuvant chemotherapy (NAC) with epirubicin and cyclophosphamide (EC) and carboplatin-paclitaxel (PC) (BSMO 2014-01)

Abstract Background: BSMO 2014-01 is a published prospective phase 2 study evaluating the efficacy of neoadjuvant EC and PC in the treatment of TNBC patients. (1) The addition of weekly carboplatin to neoadjuvant paclitaxel and dose-dense EC lead to a pathologic complete response (pCR) of 54%, comparable to prior studies. A secondary endpoint was to correlate pCR to homologous recombination (HR) and DNA damaging repair (DDR) deficiency due to germline mutations. Methods: Sixty-three patients (pts) of which nine already identified with a BRCA 1/2 mutation were considered. Peripheral blood was collected in 52 pts after obtaining informed consent for a broad genomic DNA analysis. Whole Exome Sequencing was performed, and only rare variants (M.A.F. &amp;lt;0.01) with a strong impact on protein structure (nonsense, frameshift or splice-site variants) in genes involved in DNA damage repair (DDR) were further taken into consideration. The correlation between pCR rate and DDR deficiency or deficiency in Homologous Recombination repair or HR, a subclass of DDR deficiency, was analyzed using the Fisher's exact test. Results: Twenty nine out of the 52 investigated patients carried a germline mutation in a DDR gene. Twenty of these 29 pts had a pCR, while a pCR was observed in 8/23 patients without an DDR mutation (p=0.014). In 13/15 with an HR gene mutation a pCR was obtained, while the pCR was 15/37 in pts without an HR deficiency (p=0.003). DDR deficiency not involving HR genes lead to a pCR rate of 7/14, while this was 8/23 in pts without a mutation (p= 0.3). Conclusions: This is the first genomic study in early TNBC pts which demonstrates, that a germline mutation in any of the genes involved in DNA repair by homologous recombination, strongly predicts for a pCR on neoadjuvant chemotherapy with EC and PC. Other DDR gene mutations do not predict for an enhanced pCR rate compared to pts with no DDR gene mutations identified in their germline. Ref: C. Fontaine, V. Renard, H. Van den Bulk, P. Vuylsteke et al. Weekly carboplatin plus neoadjuvant anthracycline-taxane-based regimen in early triple-negative breast cancer: a prospective phase II trial by the Breast Cancer Task Force of the Belgian Society of Medical Oncology (BSMO). Breast Cancer Res Treat 2019. Citation Format: Christel Fontaine, Vincent Renard, Heidi Van den Bulck, Peter Vuylsteke, Philippe Glorieux, Catherine Dopchie, Lore Decoster, Ahmad Awada, Hans Wildiers, Sylvie De Brakeleer, Erik Teugels, Jacques De Grève. Evaluation of germline whole exome sequencing of early breast cancer patients with triple negative breast cancer (TNBC) included in a prospective study of neoadjuvant chemotherapy (NAC) with epirubicin and cyclophosphamide (EC) and carboplatin-paclitaxel (PC) (BSMO 2014-01) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-05.

Prophylactic administration of granulocyte colony-stimulating factor in epirubicin and cyclophosphamide chemotherapy for Japanese breast cancer patients: a retrospective study.

Epirubicin and cyclophosphamide (EC) therapy, a major chemotherapy for patients with early-stage breast cancer, has a low risk (< 10%) of febrile neutropenia (FN). However, data used in reports on the incidence rate of FN were derived primarily from non-Asian populations. In this study, we investigated the FN incidence rate using EC therapy among Japanese patients with breast cancer and evaluated the significance of prophylactic administration of granulocyte colony-stimulating factor (G-CSF). We evaluated medical records of patients with early-stage breast cancer who had been treated with EC therapy as neoadjuvant or adjuvant therapy between November 2014 and July 2018. The incidence rate of FN was 23.9%. In patients who received G-CSF as primary prophylaxis, FN expression was completely suppressed. The incidence rate of severe leucopenia/neutropenia, emergency hospitalization, and the use of antimicrobial agents were low in patients receiving primary prophylaxis with G-CSF compared with those not receiving G-CSF (27.3% vs. 64.8%, 9.1% vs. 27.3%, and 27.3% vs. 71.6%, respectively). Furthermore, in all patients who received primary prophylaxis with G-CSF, a relative dose intensity > 85% using EC therapy was maintained. The incidence of FN in EC therapy among Japanese patients was higher than expected, EC therapy appears to be a high-risk chemotherapy for FN, and prophylactic administration of G-CSF is recommended. Maintaining high therapeutic intensity is associated with a positive prognosis for patients with early breast cancer, and prophylactic administration of G-CSF is likely to be beneficial in treatment involving EC therapy.

Abstract P2-08-47: Evaluation of stromal tumor-infiltrating lymphocytes (sTIL) and tertiary lymphoid structures (TLS) in early breast cancer patients with triple negative breast cancer(TNBC) included in a prospective study of neoadjuvant chemotherapy (NAC) with Epirubicin and cyclophosphamide (EC) and carboplatin-paclitaxel (PC) (BSMO 2014-01)

Abstract Background: BSMO 2014-01 is a completed prospective phase 2 study evaluating the efficacy of neoadjuvant EC and PC. One of the secondary endpoints was the correlation of sTIL with response, pCR and survival. We also assessed the relationship between sTIL and TLS in the diagnostic biopsies. Methods: Stromal TIL (sTIL) were evaluated on H&amp;E stained tumor biopsies before the start of the NAC according to the criteria described by Salgado et al(1). Scores were defined as "low" or "high" if lymphocytic infiltration in the stroma around the tumor was ≤ 10% or &amp;gt; 10%. TLS are ectopic lymph node-like structures recently identified in breast cancer. TLS were counted using a dual IHC stain for CD3 (T cells) and CD20 (B cells) and categorized as "little" if the TLS occupied &amp;lt; 10% or "moderate to abundant" if they occupied ≥ 10% of the adjacent tissue. The correlation between sTIL and pathologic parameters was analyzed using the chi-square test; DFS and OS between the groups was estimated by using the log-rank test. Results: So far we could quantify the number of sTIL in 38 out of 63 TNBC pts treated with neoadjuvant EC-PC. Twenty eight pts had a high sTIL score and 10 pts had a low sTIL score. The high-sTIL group (19/28) achieved a numerical higher pathologic complete remission (pCR) rate than the low-sTIL group (5/10) (p=0.3); both groups had a comparable disease free survival of 28.6 mths and 26.7 mths respectively (p=0.7). The overall survival was similar:29 mths and 27.8 mths respectively (p=0.8). Stromal TLS were identified in 10 out 23 samples available for this analysis and we could demonstrate a positive correlation between high levels of sTIL and high levels of moderate to abundant TLS(CD3) in the adjacent tissue in six out of the ten samples in which TLS were present (p=0.1). Conclusion: These preliminary results could not confirm the results published by Denkert et al earlier this year(2). A trend for correlation of the presence of high sTIL with moderate to abundant levels of TLS was found. Analysis on the remaining samples of all patients included in the study and correlation with outcome is ongoing and these completed results will be presented. (1)Assessing Tumor-infiltrating lymphocytes in solid tumors. Hendry S, Salgado R et al. Adv Anat Pathol 2017; 235-251. (2)Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer. Denkert C et al. Lancet Oncol 2018; 40-50. Citation Format: Fontaine C, Van den Eynden G, de Wind R, Boisson A, Renard V, Van den Bulck H, Vuylsteke P, Glorieux P, Dopchie C, Decoster L, De Grève J, Awada A, Wildiers H, Willard-Gallo K. Evaluation of stromal tumor-infiltrating lymphocytes (sTIL) and tertiary lymphoid structures (TLS) in early breast cancer patients with triple negative breast cancer(TNBC) included in a prospective study of neoadjuvant chemotherapy (NAC) with Epirubicin and cyclophosphamide (EC) and carboplatin-paclitaxel (PC) (BSMO 2014-01) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-47.

Phase II Study of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy for Operable Breast Cancer Patients (N-1 Study)

BackgroundTo improve the pathological complete response (pCR) rate, we devised new neoadjuvant chemotherapy. Efficacy and safety of the oral fluoropyrimidine derivative S-1 (Taiho Pharmaceutical Co, Tokyo, Japan) combined with low-dose docetaxel (S-1+DOC) were evaluated. Patients and MethodsPatients were treated with docetaxel (40 mg/m2 intravenously on day 1) and S-1 (40 mg/m2 orally twice per day on days 1-14) every 3 weeks for 4 cycles. In accord with the Response Evaluation Criteria In Solid Tumors version 1.1 criteria, the patients who showed a complete response (CR) underwent surgery, and those who achieved a partial response (PR) underwent 4 more cycles of S-1+DOC. Patients who achieved stable disease (SD) or progressive disease (PD) received EC (epirubicin and cyclophosphamide) or HT (trastuzumab and paclitaxel) according to their HER2 status. The primary end point was the pCR rate. ResultsNinety-four patients entered the study. After 4 cycles of S-1+DOC, CR was noted in 5 patients, PR in 57, SD in 18, and PD in 3. Of the patients who achieved SD and PD, 12 received EC, and 9 received HT. Among the 83 assessable patients, the pCR rate was 34.9%, and the response rate was 80.7%. The pCR rates were 19.5% in the luminal type group, 53.8% in the luminal HER2 group, 46.1% in the HER2 group, and 50.0% in the triple-negative group. ConclusionThe S-1+DOC regimen in this study could be well tolerated and a new candidate neoadjuvant chemotherapy in operable breast cancer patients. It is also expected to be effective even in patients with luminal type disease. However, further randomized control trials are needed to ascertain whether pCR can contribute to favorable outcomes.

Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer

PurposeAlthough adjuvant polychemotherapy improves outcomes for early breast cancer, the significant variability in terms of pharmacokinetics results in differences in efficacy and both short and long-term toxicities. Retrospective studies support the use of dose tailoring according to the hematologic nadirs.MethodsThe SBG 2004-1 trial was a randomized feasibility phase II study which assessed tailored dose-dense epirubicin and cyclophosphamide (EC) followed by docetaxel (T) (group A), the same regimen with fixed doses (group B) and the TAC regimen (group C). Women aged 18–65 years, ECOG PS 0-1 with at least one positive axillary lymph node were randomized 1:1:1. The primary endpoint of the study was the safety and feasibility of the treatment. Toxicity was graded according to CTC-AE version 3.0. The design and short-term toxicity have been previously published. Here, we report safety and efficacy data after 10 years of follow-up.ResultsA total of 124 patients were included in the study. After a median follow-up of 10.3 years, the probability for 10-year survival was 78.5, 75.1, and 63.4% and for relapse free survival 64.1, 71.0, and 59.5% for groups A, B, and C, respectively. There were no cases of clinically diagnosed cardiotoxicity or hematologic malignancies. No patient was lost to follow-up.ConclusionsIn this randomized phase II trial, tailored dose adjuvant chemotherapy was feasible, without an increased risk for long-term adverse events after a median follow-up of 10 years.

Long-term safety and survival outcomes from the Scandinavian Breast Group 2004–1 (SBG 2004-1) randomized trial of tailored dose adjuvant chemotherapy for early breast cancer.

e12036 Background: Although adjuvant polychemotherapy (ACT) improves outcomes for early breast cancer (BC), the significant interpatient variability in pharmacokinetics result in differences in efficacy and both short and long term toxicities. Dose tailored ACT has been shown to improve outcomes, while tailored and dose dense therapy improved 5-year event free survival in the phase 3 PANTHER trial. Methods: The SBG 2004-1 trial was a randomized feasibility/phase II study which assessed dose tailored epirubicin and cyclophosphamide (EC) followed by docetaxel (T), compared to the same fixed dose schedule and to the TAC regimen (table 1). Women aged 18-65 years old, ECOG PS 0-1 with at least one positive lymph node were randomized 1:1:1. The primary endpoint of the study was the safety and feasibility of the administered treatment. The secondary endpoint of the study was to evaluate the dose-intensity of the treatment. Toxicity was graded according to CTC-AE version 3.0. The design and short-term safety results of the trial have been previously published. Here, we report safety and efficacy data after 10 years follow-up. Results: A total of 124 patients were included and &gt;95% of patients without relapse were followed for 10 years.Five secondary malignancies but no myelodysplastic syndrome / acute myeloid leukemias were reported. Long term disease-free and overall survival results will be presented at the meeting. Conclusions: Long term safety results from this study in combination with efficacy results from the PANTHER trial imply the feasibility of a tailor-based approach for ACT in early BC. [Table: see text]

P017 - Safety and tolerance of dose-dense Epirubicin and Cyclophosphamide (EC) with Pegfilgrastim for Japanese patients with early breast cancer

P017 - Safety and tolerance of dose-dense Epirubicin and Cyclophosphamide (EC) with Pegfilgrastim for Japanese patients with early breast cancer