Final report and long-term outcomes: Phase I trial of a HER2 intracellular plasmid-based vaccine in HER2+ advanced stage breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2619-2619
Author(s):  
Mary L. Disis ◽  
Yushe Dang ◽  
Andrew L. Coveler ◽  
Doreen Higgins ◽  
Jennifer Childs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Optimal Dose ◽  
P Value ◽  
Final Report ◽  
Linear Regression Models ◽  
Her2 Breast Cancer ◽  
Kaplan Meier ◽  
Number Of Patients ◽  
Vaccine Site

2619 Background: Vaccination with the intracellular domain (ICD) of HER2 in pre-clinical models is both immunogenic and protective against the development of mammary tumors. This study (NCT00436254) was designed to examine the safety and optimal immunogenic dose of a DNA-based vaccine encoding the HER2 ICD in subjects with HER2+ breast cancer. Methods: Sixty-six patients with stage III or IV HER2 + breast cancer in remission or with stable bone only disease were enrolled into three vaccine arms: 1 (10mcg dose of plasmid), 2 (100mcg) and 3 (500mcg). Vaccines were administered i.d. monthly for three immunizations. Endpoints included safety and optimal dose. HER2 specific IFN-gamma immune responses were evaluated and DNA persistence at the vaccine site was assessed. Toxicity and clinical outcomes were followed for 10 years. Results: The majority of vaccine-related toxicity was grade 1 (89%) and grade 2 (11%) and was not significantly different between the three dose arms. All Arms developed HER2 ICD immunity after vaccination, however, patients in Arm 2 and Arm 3 had significantly better immune responses (of higher magnitude and at most time points) than patients in Arm 1 (p=0.003 and p<0.001, respectively) after adjusting for baseline factors. At 60 weeks, the number of patients who maintained the greatest fold-difference in HER2 ICD immune responses from their baseline was highest in Arm 2 (73%) when compared to Arm 1 (47%) and Arm 3 (45%). Associations between ICD responses and plasmid DNA persistence at the vaccine site were estimated via linear regression models. HER ICD immunity after the end of immunizations, relative to baseline, was significantly lower in patients with DNA persistence at week 16 compared to those without persistence (p=0.02). Patients at the highest dose demonstrated the greatest incidence of plasmid persistence (92%) as compared to 33% in Arm 1 and 10% in Arm 2. The median time of follow-up was 118.6 months (Arm 1), 99.7 months (Arm 2), and 73.5 months (Arm 3). The median OS and PFS has not been reached in any Arm and did not differ with respect to treatment arm (Log-rank p-value 0.36 for OS, and 0.63 for PFS). However, we observed a separation of Kaplan-Meier curves for OS from about 40 months and curves for PFS from about 30 months, and the separation maintained until the end of the study for Arm 2 versus Arm 1 and Arm 3. One patient in Arm 2 developed lymphocytic colitis 2.2 years from enrollment deemed possibly related to vaccination. Conclusions: An intermediate dose (100mcg) of vaccine was immunogenic and associated with persistence of immunity at 60 weeks. A randomized phase II trial of the HER2 ICD plasmid-based vaccine in the neoadjuvant setting is in development. Clinical trial information: NCT00436254.

A phase I study of a DNA plasmid based vaccine encoding the HER2/neu (HER2) intracellular domain (ICD) in subjects with HER2+ breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3054-3054
Author(s):  
L. G. Salazar ◽  
M. Slota ◽  
D. Wallace ◽  
D. Higgins ◽  
A. L. Coveler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Phase I ◽  
Plasmid Dna ◽  
Phase I Study ◽  
Rt Pcr ◽  
Gm Csf ◽  
Her2 Breast Cancer ◽  
Vaccine Site ◽  
Dna Plasmid

3054 Background: HER2 is overexpressed in 25% of breast cancers and plays a role in the malignant transformation of cells. Vaccine-induced immunity against the HER2 ICD correlates with antitumor responses in animal models. DNA-based vaccines offer a strategy to immunize against multiple tumor antigens and are able to elicit both CTL and T helper immune responses. Plasmid DNA can also remain at the vaccine site, providing a constant source of antigen. However, DNA vaccines have been poorly immunogenic due in part to inefficient APC transfection. Intradermal (i.d.) delivery of DNA vaccines with GM-CSF as adjuvant may enhance immunogenicity due to local influx of dermal Langerhans cells. A phase I study was conducted to evaluate the safety and immunogenicity of a DNA-based vaccine encoding the HER2 ICD. Methods: 44 subjects with stage III and IV HER2+ breast cancer in complete remission were enrolled sequentially into 2 vaccine arms (22 subjects/arm) and received 10μg pNGVL3-hICD (Arm 1) or 100μg pNGVL3-hICD (Arm 2). All vaccines were admixed with 100μg GM-CSF and given i.d. monthly for a total of 3 vaccines. Toxicity was assessed at baseline, during vaccination, and at follow-up. Immune responses were assessed with IFN-γ ELISPOT at baseline and post-vaccination. Vaccine site biopsies were analyzed for plasmid persistence via RT-PCR, 1 and 6 months after vaccination. Results: 43 subjects (21 in Arm 1; 22 in Arm 2) completed 3 vaccines. Vaccine-related toxicity in both arms was primarily grade I/II; no cardiac or grade IV toxicity was observed. 13/21 (62%) subjects in Arm 1 developed T-cell immunity, defined as HER2-specific T cell precursors:PBMC, to the HER2 protein (median 1:5,972, range 1:717–1:3,000,000) and to p776, a HER2 pan DR binding epitope (median 1:3,150, range 1:543–1:108,696). 13/19 (68%) subjects in Arm 1 had persistent plasmid DNA at the vaccine site. ELISPOT and RT-PCR analysis for Arm 2 are on-going. Conclusions: Immunization with a DNA plasmid-based HER2 vaccine is safe and immunogenic. Moreover, plasmid DNA persists at the vaccine site post-immunization and HER2+ cancer patients are able to develop immunity to the HER2 ICD. No significant financial relationships to disclose.

Randomized, Controlled, Dose-Range Study of Ro 25-8315 Given Before and After a High-Dose Combination Chemotherapy Regimen in Patients With Metastatic or Recurrent Breast Cancer Patients

2002 ◽  
Vol 20 (1) ◽  
pp. 24-36 ◽  
Author(s):  
P. Viens ◽  
C. Chabannon ◽  
P. Pouillard ◽  
M. Janvier ◽  
W. Brugger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Progenitor Cell ◽  
Chemotherapy Regimen ◽  
Single Injection ◽  
Optimal Dose ◽  
High Dose ◽  
Breast Cancer Patients ◽  
Number Of Patients ◽  
Cell Mobilization

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients. PATIENTS AND METHODS: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 μg/kg, n = 9; 60 μg/kg, n = 9; 100 μg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 μg/kg/d; part II, 5 μg/kg/d) (control group, n = 8). RESULTS: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 μg/kg. The peak of circulating CD34+ cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 × 109/L by day +15. In part II, high levels of circulating CD34+ cells (> 20 cells/μL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 × 109/L) was similar in the four groups. Ro 25-8315 100 μg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 × 109/L on day +12 after chemotherapy. CONCLUSION: A single injection of Ro 25-8315 100 μg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 μg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen.

Nephrectomy status, race, and overall survival in patients with metastatic renal cell carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 529-529
Author(s):  
Dale Kesley Robertson ◽  
Chao Zhang ◽  
Yuan Liu ◽  
Theresa Wicklin Gillespie ◽  
Omer Kucuk ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Median Overall Survival ◽  
P Value ◽  
Kaplan Meier ◽  
Number Of Patients ◽  
Emory University

529 Background: In most settings median overall survival (OS) is longer for non-Hispanic whites relative to non-Hispanic blacks with metastatic renal cell carcinoma (mRCC). However, absence of nephrectomy has been a predictor of shorter OS for both groups. The primary objectives of this study were to define the reasons why patients with mRCC do not undergo nephrectomy and to correlate absolute contraindications to surgery with race and OS. Methods: Retrospective chart reviews of patients treated with targeted therapy for mRCC were conducted at the Winship Cancer Institute of Emory University and the AVAMC after obtaining institutional authorizations. Reasons for not undergoing nephrectomy were categorized as absolute, relative or no contraindication to nephrectomy. Descriptive statistics were employed along with Kaplan-Meier survival analysis. Results: See Table. The median OS (months) by nephrectomy status was 15.9 (6.8 – 24.7) vs. 41.8 (25.6 – 49.4), p value 0.0003, for patients at Emory with no nephrectomy vs. nephrectomy, respectively. The corresponding AVAMC values were 15.5 (8.5 – 29.5) vs. 45.2 (30.3 – 100.9), p value 0.0002. Conclusions: The number of patients with absolute contraindications to nephrectomy varied widely by race and institution, yet absence of nephrectomy was the predominant predictor of shorter OS in both settings. [Table: see text]

Phase II study of preoperative chemotherapy versus standard postoperative chemotherapy in HR-negative HER2-positive breast cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12118-e12118
Author(s):  
Meng Xiu ◽  
Pin Zhang
Keyword(s):  
Breast Cancer ◽  
Preoperative Chemotherapy ◽  
Postoperative Chemotherapy ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Risk Patients

e12118 Background: HR-/HER2+ breast cancer is a subtype with aggressive characteristic and poor survival. More clinical evidence are needed for choice of therapeutic strategies. Methods: Patients with T1-3N0-3M0 received preoperative chemotherapy (PTX 175 mg/m2, CBP AUC 4, q2w*6) combined with trastuzumab (2mg/kg qw) or standard postoperative chemotherapy such as ddAC-PH, AC-PH, TCH. The primary endpoint was RFS. Results: 86 patients were enrolled, 43 received preoperative chemotherapy (pre arm) and the other 43 received postoperative chemotherapy (post arm). There was no significant difference in baseline between the two arms. 22.1% of patients were stage IIA, 25.6% IIB, 34.9% IIIA, and 18.6% IIIC. At a median follow-up of 33.4 months, 16 patients had relapsed (pre arm 8, post arm 8). The median time from diagnosis to relapse was 22.8 months (7.1-49.2) and 23.8 months (11.4-37.4) in pre and post arm. Kaplan-Meier survival analysis estimated that the 3-year RFS were similar (pre vs post: 73.4% vs 75.4%, p= 0.631). Only 1 death occurred in post arm. Table showed that in subgroups, there was no statistical difference in risk of recurrence between pre and post arms. In pre arm, ORR was 97.7% clinically, and pCR (ypT0/TisN0) was 39.0%. No patients achieved pCR relapsed, and the residual invasive lesions indicated poor prognosis. Table showed that Neo-Bioscore 4-5 was related to recurrence event significantly ( p= 0.021). The rate of breast-conserving in pre arm was higher (19.5% vs 9.3%), and PCb regiments every 2 weeks had similar adverse effects with standard chemotherapy, and less patients had dose reductions (18.6% vs 25.6%). Conclusions: Preoperative chemotherapy versus standard postoperative chemotherapy results in similar RFS among HR-/HER2+ patients. Preoperative chemotherapy can identify prognosis of patients early by Neo-Bioscore and adjuvant therapy should be strengthened for high-risk patients. PCb every 2 weeks combined with trastuzumab can be an option of preoperative therapy for HER2+ breast cancer. Clinical trial information: NCT02934828. [Table: see text]

The effect of trastuzumab on pCR in locally advanced HER2-positive breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 286-286
Author(s):  
S. M. Lavasani ◽  
K. I. Pritchard ◽  
A. Kiss ◽  
S. Verma ◽  
F. Wright ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Cancer Center ◽  
P Value ◽  
Her2 Positive ◽  
Primary Tumors ◽  
Her2 Breast Cancer ◽  
Baseline Characteristics

286 Background: Neoadjuvant therapy (NAT) is now standard of care for locally advanced breast cancer (LABC). Evidence shows that pathological complete response (pCR) predicts for disease free and overall survival. The pCR rates for LABC vary widely in the literature but prognosis still remains poor for this group of pts. Increases in pCR have been reported in clinical trials with the addition of trastuzumab (T) but these studies have predominantly included operable pts. The aim of this study was to evaluate whether the addition of T to NAT has improved the rates of pCR in HER2+ LABC pts at our center. Methods: Pts from the LABC prospective database at the Sunnybrook Odette Cancer Center in Toronto were included if they had confirmed HER2+ LABC [primary tumors greater than 5cm (T3) with skin or chest wall involvement (T4) or with matted axillary adenopathy (N2)]. Two cohorts of LABC pts, pre-T and post-T groups were compared for baseline characteristics and pCR. Chi square tests and p values were used for comparing proportions. Results: 43 pts were diagnosed between Jan 2002 to Dec 31, 2006 who had HER2+ breast cancer and received NAT without T (pre-T cohort). 17 HER2+ pts were diagnosed with LABC between Jan 1, 2007 to Dec 31, 2009 who received neoadjuvant T (post-T cohort). Baseline characteristics were similar in two cohorts (Table) except more pts in pre-T cohort received neoadjuvant hormonal therapy. The rate of pCR in the pre-T cohort was 9.3% and in the post-T cohort 29% (p value=0.02). Conclusions: The pCR rate dramatically improved in our LABC patients with the addition of T to NAT. The pCR rates still remain lower than in published clinical trials likely reflecting the more advanced nature of LABC in clinical practice. [Table: see text]

scholarly journals Paclitaxel Promotes Tumor-Infiltrating Macrophages in Breast Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382094582
Author(s):  
Jun Shen ◽  
Cong Chen ◽  
Zhaoqing Li ◽  
Shufang Hu
Keyword(s):  
Breast Cancer ◽  
Progression Free Survival ◽  
Cancer Prognosis ◽  
Migration And Invasion ◽  
P Value ◽  
Free Survival ◽  
Kaplan Meier ◽  
The Relationship ◽  
Kaplan Meier Plotter ◽  
Paclitaxel Treatment

Objective: Breast cancer remains the most threatening triggers of cancer death in women. Drug resistance inevitably leads to the weakness of treatment for breast cancer. Macrophages, as one of the most abundant immune cells in tumor immune-infiltrating microenvironment, involves in cell survival, migration, and invasion of breast cancer. Methods: In this study, we compared the proportions of macrophages in patients with breast cancer with and without paclitaxel treatment, and investigated the targeted genes associated with macrophages for paclitaxel response. To explore the relationship between drug-related genes and breast cancer prognosis, survival analysis based on the drug-related genes were performed by website of Kaplan-Meier plotter with the threshold of significant P value < .05. Results: Compared to the normal samples, we revealed that paclitaxel significantly enhanced the ratio of macrophages in the tumor microenvironment. Furthermore, the expression of 3 drug-related genes (IFT46, PEX11A, and TMEM223) were significantly negatively associated with the proportions of macrophages. And it is worth to notice that PEX11A and TMEM223 were associated with better progression-free survival outcomes of patients with breast cancer. Moreover, PEX11A was associated with longer overall survival time of breast cancer. Conclusion: Taken all together, all the findings support to gain a better understanding to the development of more effective therapies targeted with paclitaxel.

scholarly journals MZ1 co-operates with trastuzumab in HER2 positive breast cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
María del Mar Noblejas-López ◽  
Cristina Nieto-Jiménez ◽  
Eva M. Galán-Moya ◽  
David Tebar-García ◽  
Juan Carlos Montero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Subtype ◽  
Three Dimensional ◽  
In Vivo Studies ◽  
Breast Cancer Cell Lines ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Number Of Patients ◽  
Bet Inhibitors

Abstract Background Although the anti-HER2 antibody trastuzumab augments patient survival in HER2+ breast cancer, a relevant number of patients progress to this treatment. In this context, novel drug combinations are needed to increase its antitumor activity. In this work, we have evaluated the efficacy of proteolysis targeting chimera (PROTAC) compounds based on BET inhibitors (BETi) to augment the activity of trastuzumab in HER2+ breast cancer models. Methods BT474 and SKBR3 HER2+ breast cancer cell lines were used. The effects of trastuzumab and the BET-PROTAC MZ1 either alone or in combination, were evaluated using MTT proliferation assays, three-dimensional invasion and adhesion cultures, flow cytometry, qPCR and Western blot. In vivo studies were carried out in a xenografted model in mice. Finally, a Clariom_S_Human transcriptomic array was applied to identify deregulated genes after treatments. Results MZ1 induced a higher antiproliferative effect compared to the BETi JQ1. The combination of MZ1 and -trastuzumab significantly decreased cell proliferation, the formation of three-dimensional structures and cellular invasion compared to either of the drugs alone. Evaluation of apoptosis resulted in an increase of cell death following treatment with the combination, and biochemical studies displayed modifications of apoptosis and DNA damage components. In vivo administration of agents alone or combined, to tumors orthotopically xenografted in mice, resulted in a decrease of the tumor volume only after MZ1-Trastuzumab combination treatment. Results from a transcriptomic array indicated a series of newly described transcription factors including HOXB7, MEIS2, TCERG1, and DNAJC2, that were associated to poor outcome in HER2+ breast cancer subtype and downregulated by the MZ1-trastuzumab combination. Conclusions We describe an active novel combination that includes the BET-PROTAC MZ1 and trastuzumab, in HER2+ tumors. Further studies should be performed to confirm these findings and pave the way for their future clinical development.

scholarly journals Differences in clinicopathological features and molecular phenotype of breast carcinoma between patients younger than 40 years and those who are older: A study from Pakistan

2020 ◽  
Author(s):  
Romana Idress ◽  
Faiza Rasheed ◽  
Jamshid Abdul-Ghafar ◽  
Abida Sattar ◽  
Zubair Ahmad
Keyword(s):  
Breast Cancer ◽  
Lymphovascular Invasion ◽  
Cross Sectional Study ◽  
Clinicopathological Features ◽  
P Value ◽  
Axillary Lymph ◽  
Cross Sectional ◽  
Axillary Lymph Node Metastases ◽  
Number Of Patients ◽  
Clinicopathological Variables

Abstract Background The debate whether breast cancer in women under 40 years of age is distinct from breast cancer in women above 40 is still inconclusive with various published studies providing conflicting evidence. The majority of studies however suggest that breast cancer in younger women (< 40) is more aggressive with worse clinicopathological features. However, the issue is by no means settled and a number of studies are still going on. Our objective was to analyze different clinicopathological variables and determine whether statistically significant differences are present between those under 40 and those above 40 years of age. The present paper contributes to this debate by reporting our findings. Methods Descriptive cross sectional study of 482 breast cancer cases reported between January and December 31, 2016 which included 380 patients (above 40 years of age) and 102 (under 40 years of age). Variables included grade, stage, axillary lymph node metastases, lymphovascular invasion and molecular groups. p-value less than 0.05 was taken as significant. Results Over 21% patients were younger than 40 years. Differences in histologic grade, stages of T1, T2, and T4, Estrogen Receptor (ER) and Progesterone Receptor (PR) status, Her2neu status, triple negativity and molecular groups between patients younger than 40 years and those older than 40 years were statistically insignificant. Differences in stage T3, axillary metastases and lymphovascular invasion were statistically significant. Conclusion Statistically significant differences were noted in some clinicopathological variables. Majority of variables indicating more aggressive disease were seen in patients older than 40 years of age. Additional studies with larger number of patients under 40 years of age are required to resolve the issue conclusively so that young women with breast cancer are not treated too aggressively unless there is unequivocal statistical evidence that breast cancer is more aggressive in patients under 40 years of age.

scholarly journals The Deubiquitinating Enzyme UCHL1 Induces Resistance to Doxorubicin in HER2+ Breast Cancer by Promoting Free Fatty Acid Synthesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Guangxian Lu ◽  
Jianhua Li ◽  
Leyun Ding ◽  
Chenping Wang ◽  
Lian Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Poor Prognosis ◽  
Acid Synthesis ◽  
Rank Test ◽  
Deubiquitinating Enzyme ◽  
Her2 Breast Cancer ◽  
Kaplan Meier ◽  
Mcf 7

Ubiquitin C-terminal hydrolase L1 (UCHL1), which is a deubiquitinating enzyme, is known to play a role in chemoresistance in cancers. However, its potential roles and mechanisms in the chemoresistance of breast cancer (BC) remain unclear. In this study, we examined its expression in patients with BC and employed Kaplan–Meier analysis and the log-rank test for survival analyses. It was found that up-regulated UCHL1 expression was positively associated with both chemoresistance and poor prognosis, especially in patients with HER2+ BC. Moreover, UCHL1 expression was elevated in HER2+ BC cells (SK-BR-3 and BT474). Similarly, doxorubicin (DOX)-resistant BC cells (MCF-7/DOX) had higher UCHL1 levels than MCF-7 cells. CCK-8 assay showed that BC cells with higher UCHL1 levels were more resistant to DOX. Furthermore, by inhibiting UCHL1 in BC cells with elevated UCHL1 expression, we demonstrated that UCHL1 promoted DOX-resistance in BC. Mechanistically, UCHL1 probably promoted DOX-resistance of BC by up-regulating free fatty acid (FFA) synthesis, as exhibited by reduced FFA synthase expression and resurrected DOX-sensitivity upon UCHL1 inhibition. Overall, UCHL1 up-regulation is associated with DOX-resistance and poor prognosis in patients with HER2+ BC. UCHL1 induces DOX-resistance by up-regulating FFA synthesis in HER2+ BC cells. Thus, UCHL1 might be a potential clinical target for overcoming DOX resistance in patients with HER2+ BC.

Phase II study of adjuvant endocrine therapy with CDK 4/6 inhibitor, ribociclib, for localized ER+/HER2- breast cancer (LEADER).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 531-531
Author(s):  
Laura Spring ◽  
Colleen Griffin ◽  
Steven J. Isakoff ◽  
Beverly Moy ◽  
Seth Andrew Wander ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Endocrine Therapy ◽  
Phase Ii ◽  
Adjuvant Endocrine Therapy ◽  
Adjuvant Setting ◽  
Her2 Breast Cancer ◽  
Number Of Patients ◽  
Grade 3 ◽  
One Year

531 Background: Given the success of CDK 4/6 inhibitors for ER+/HER2- metastatic breast cancer, there is much interest in exploring these agents in early breast cancer to potentially reduce recurrence risk. However, tolerability and adherence are important considerations in the adjuvant setting. We evaluated the tolerability and adherence of adjuvant endocrine therapy with the CDK 4/6 inhibitor, ribociclib, in two different schedules, in a prospective phase II clinical trial. Methods: Eligible patients were those with localized stage I-III ER+ (≥ 10%), HER2- breast cancer who had completed surgery and were on adjuvant endocrine therapy with at least one year or more of treatment remaining. Patients were randomized to receive continuous ribociclib (400 mg daily of 28-day cycle; arm 1) or intermittent ribociclib (600 mg daily on days 1-21 of 28-day cycle; arm 2) for one year, in addition to an aromatase inhibitor (plus GnRH agonist if premenopausal). Toxicities were evaluated using CTCAE version 4.03. Adherence was monitored by review of patient diaries and pill count. Results: Of the 81 patients enrolled, 24 discontinued early. The table shows the current status of the patients based on treatment arm (data cut-off as of 1/31/20; updated results will be presented at meeting). A total of 8 serious adverse events (AEs) have occurred thus far: grade 3 transaminitis (1), grade 4 transaminitis (3), grade 3 colitis (1), grade 3 infection (2), and grade 4 lymphopenia (1). The most common grade 3 or greater AEs leading to study discontinuation thus far were transaminitis (8.6%), neutropenia (2.5%), and fatigue (2.5%). No patients discontinued early due to prolonged QTc. Adherence results will be reported at the meeting. Conclusions: Interim results demonstrate that while serious AEs with one year of adjuvant ribociclib are low, a number of patients discontinued adjuvant CDK 4/6 inhibitor. Tolerability and adherence patterns will need to be carefully considered with CDK 4/6 inhibitors in the adjuvant setting. Clinical trial information: NCT03285412 . [Table: see text]

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