Trastuzumab deruxtecan for HER2+ advanced breast cancer

2021 ◽  
Author(s):  
Jiyun Lee ◽  
Yeon Hee Park
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancer Patients ◽  
Antibody Drug Conjugate ◽  
Metastatic Setting ◽  
Clinical Benefits

Trastuzumab deruxtecan (T-DXd, DS-8201), an anti-HER2 antibody–drug conjugate, has shown significant clinical benefits in HER2+ metastatic breast cancer patients. In the phase 2 DESTINY-Breast01 trial, T-DXd demonstrated an objective response of 60.9% and median progression-free survival of 16.4 months, laying the foundation for accelerated approval in HER2+ metastatic breast cancer patients who have received two or more prior anti-HER2-based regimens in the metastatic setting. Moreover, T-DXd exhibited promising antitumor efficacy against HER2-low-expressing metastatic breast cancer. Its distinctive side effect was pneumonitis, with a 13.6% incidence. It is approved in the US with boxed warnings for interstitial lung disease and embryo–fetal toxicity. This review focuses on preclinical, pharmacokinetic and pharmacodynamic data on T-DXd and clinical evidence of its antitumor activity (both as monotherapy and in combination) and tolerability in metastatic breast cancer.

The combination of capecitabine and cyclophosphamide for metastatic breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12025-e12025
Author(s):  
M. Suzuki ◽  
I. Kimijima ◽  
M. Ishii
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Medical Center ◽  
Objective Response ◽  
Metastatic Breast ◽  
Complete Response ◽  
Preclinical Study ◽  
Synergistic Activity ◽  
Breast Cancer Patients

e12025 Background: Capecitabine (X) is converted into 5-FU by thymidine phospholylase (TP). Cyclophosphamide (C) has been shown to make TP higher in the preclinical study. Therefore, the combination of capecitabine and cyclophosphamide (XC) is thought to have a synergistic activity. We explored the efficacy of XC for metastatic breast cancer patients. Methods: 50 metastatic breast cancer patients were treated with XC in our medical center between April 2004 and December 2008. Median patient age was 58 years old (range: 34–79 years old). 36 patients were postmenopausal. X was 1675mg/m2 days 1–21 and C was 67mg/m2 days 1–14 on a 28-day cycle in all-oral combination. This therapy was continued until progression of disease or unacceptable toxicities occurring. Results: Median time to treatment failure was 28 weeks (range: 2–158 weeks). 9 patients were not evaluable for tumor response. Among 41 evaluable patients, complete response (CR) was observed in 2.4% (1 patient) and partial response (PR) was 29.2% (12 patients). Stable disease (SD) was 41.4% (17 patients) and progression of the disease (PD) was 26.8% (11 patients). The objective response rate (CR+PR) was 31.7% and the overall clinical benefit (CR+PR+SDÅÜ24 weeks) was 53.6%. Significant toxicities were uncommon: grade 3 toxicities were encountered for neutropenia in 1 patient, anorexia in 1 patient and hand-foot syndrome in 2 patients. Conclusions: XC is an effective regimen in metastatic breast cancer, and this therapy is of an easy administration and very well tolerated. No significant financial relationships to disclose.

Outcome of palbociclib based therapy in hormone receptor positive metastatic breast cancer patients after treatment with everolimus.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1054-1054 ◽  
Author(s):  
Ajay Dhakal ◽  
Christina Matthews ◽  
Fan Zhang ◽  
Ellis Glenn Levine ◽  
Stephen B. Edge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Clinical Benefit ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive ◽  
Metastatic Setting

1054 Background: Resistance mechanisms to CDK 4/6 inhibition are not well defined. Outcome data on hormone receptor positive (HR+) metastatic breast cancer patients (MBCP) treated with palbociclib (PA) after treatment with everolimus (EV) are lacking. The PALOMA 3 trial (P3) showing benefit of PA plus fulvestrant (FU) compared to FU in HR+ MBCP after progression on endocrine therapy excluded women previously treated with EV. The aim of our study was to investigate the outcomes of HR+ MBCP with prior EV treatment on PA based therapy. Methods: This is a retrospective, single institute review of HR+, HER 2 nonamplified MBCP from Jan 2014 - Nov 2016 treated with PA after treatment with EV. Women who received EV for < 1 month or PA < 14 days were excluded. Progression free survival (PFS) was defined as the time from the initiation of PA to the date of progression as determined by treating physician based on radiological, biochemical and/or clinical criteria. Response rates were determined based on available radiological data. Clinical benefit was defined as a complete response (CR), partial response (PR) or stable disease of at least 24 weeks. Results: 23 patients with mean age 67 years (42 to 81) were identified. 95% were postmenopausal, 81% had ECOG performance status 0 or 1, 83% had visceral metastases, 95% had > 2 lines of prior endocrine therapy (ET), 82% shown prior sensitivity to ET, 82% received prior chemotherapy, of which 84% were in metastatic setting. Kaplan Meier estimate showed median PFS of 2.9 months (95% CI 2.0-4.2); median PFS of P3 PA cohort was 9.5 months (95% CI 9.2-11.0). Fisher’s exact test comparing study cohort with P3 PA cohort showed statistically significant differences in objective response (CR or PR) rates of 0/23 (0%) vs. 66/347 (19%, p = 0.02) & clinical benefit ratio of 4/23 (17.4%) vs. 231/347 (66.5%, p = 0.00). Conclusions: Outcomes with PA in HR+ EV treated MBCP were worse when compared to the P3 PA cohort data. Treatment with EV may lead to resistance to CDK inhibition. Though limited by size, our data suggests that use of PA after EV is associated with low response & clinical benefit rates. Further studies are necessary to confirm the findings to determine sequencing of targeted therapies.

Gemcitabine and Vinorelbine Combination Chemotherapy in Taxane-Pretreated Patients with Metastatic Breast Cancer: A Phase II Study of the Kinki Multidisciplinary Breast Oncology Group (KMBOG) 1015

Chemotherapy ◽  
2017 ◽  
Vol 62 (5) ◽  
pp. 307-313 ◽  
Author(s):  
Jun Yamamura ◽  
Norikazu Masuda ◽  
Daigo Yamamoto ◽  
Shigeru Tsuyuki ◽  
Masahide Yamaguchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival

Background: This phase II study was conducted to evaluate the efficacy and safety of the chemotherapy combination of gemcitabine and vinorelbine in taxane-pretreated Japanese metastatic breast cancer patients. Methods: In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2-negative breast cancer were administered gemcitabine (1,200 mg/m2) and vinorelbine (25 mg/m2) intravenously on days 1 and 8 every 3 weeks. The primary endpoint was the objective response rate, and other endpoints included progression-free survival, overall survival, and safety. Results: A total of 42 patients were enrolled in this study. The objective response rate and clinical benefit rate were 24 and 43%, respectively. The median progression-free survival was 4.0 months. The median overall survival was 11.1 months. Grade 3/4 neutropenia was the most common hematologic toxicity, occurring in 22 patients (54%). Nonhematologic toxicity was moderate and transient, with fatigue (48%) being the most common condition and no severe adverse event reported. Conclusion: The combination of gemcitabine and vinorelbine is an effective and tolerable regimen for HER2-negative, taxane-pretreated, metastatic breast cancer patients in Japan.

The impact of waist-to-hip ratio (WHR) on survival in metastatic breast cancer patients treated with aromatase inhibitors (AIs)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1070-1070
Author(s):  
M. Artac ◽  
M. Samur ◽  
H. Bozcuk ◽  
B. Afacan ◽  
M. Ozdogan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Fat Distribution ◽  
Abdominal Fat ◽  
Rank Statistic ◽  
Breast Cancer Patients ◽  
Free Survival

1070 Background: Aromatase inhibitors represent a novel hormonal therapy for breast cancer. Aromatase is expressed in the ovaries, brain, bone and, adipose and breast tissue. Elevated WHR, representing a higher abdominal fat distribution, has been associated with both the development of and mortality from breast cancer. Therefore, we aimed to identify whether abdominal fat distribution could affect the outcome in metastatic breast cancer patients treated with AIs. Methods: A total of 46 metastatic breast cancer patients treated with first line hormonal therapy were enrolled in this study. Pretreatment body weight, height, BMI and WHR were measured. Estrogen, progesteron and c- erb-B2 receptor status were also evaluated in analyses. Univariate and multivariate Cox regression analyses, and Kaplan Meier survival curves subjected to log rank testing were utilized for the survival analyses. Forward likelihood ratio was used for the multivariate selection process. A P value < 0.05 was considered to be significant. Results: Median age was 51 years (range 28 - 75). 36 patients were treated with letrozole and 10 patients with anastrozole. Median body weight, height, WHR and BMI were found to be 68.5 kg (range 46 - 115), 156 cm (range 137 - 167), 0.91 (range 0.7 - 1.2), and 28.7 (range 18 - 45), respectively. Factors associated with overall survival in the univariate analysis were age, c-erb-B2 expression intensity (+++ versus others by immunohistochemistry), and WHR, whereas only WHR retained significance in the multivariate analysis. Likewise, predictors of progression free survival were c-erb-B2 expression intensity and WHR. However, none of these factors was significant in the multivariate analysis. Median overall survival figures were 472 days versus unreached for patients with a WHR of <0.92 and =0.92 (Log rank statistic = 9.76, P = 0.002). Similarly, the corresponding progression free survival figures for patients with a WHR of <0.92 and =0.92 were 423 versus 1,004 days (Log rank statistic = 6.37, P = 0.012). Conclusions: This is the first report examining and suggesting the value of abdominal fat distribution in relation with benefit from AIs in metastatic breast cancer. Our results should be validated in larger series. No significant financial relationships to disclose.

scholarly journals Untargeted Assessment of Tumor Fractions in Plasma for Monitoring and Prognostication from Metastatic Breast Cancer Patients Undergoing Systemic Treatment

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1171 ◽  
Author(s):  
Christoph Suppan ◽  
Iva Brcic ◽  
Verena Tiran ◽  
Hannah D Mueller ◽  
Florian Posch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Effective Means ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Close Correlation ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Z Scores

The aim of this study was to assess the prognostic and predictive value of an untargeted assessment of tumor fractions in the plasma of metastatic breast cancer patients and to compare circulating tumor DNA (ctDNA) with circulating tumor cells (CTC) and conventional tumor markers. In metastatic breast cancer patients (n = 29), tumor fractions in plasma were assessed using the untargeted mFAST-SeqS method from 127 serial blood samples. Resulting z-scores for the ctDNA were compared to tumor fractions established with the recently published ichorCNA algorithm and associated with the clinical outcome. We observed a close correlation between mFAST-SeqS z-scores and ichorCNA ctDNA quantifications. Patients with mFAST-SeqS z-scores above three (34.5%) showed significantly worse overall survival (p = 0.014) and progression-free survival (p = 0.018) compared to patients with lower values. Elevated z-score values were clearly associated with radiologically proven progression. The baseline CTC count, carcinoembryonic antigen (CEA), and cancer antigen (CA)15-5 had no prognostic impact on the outcome of patients in the analyzed cohort. This proof of principle study demonstrates the prognostic impact of ctDNA levels detected with mFAST-SeqS as a very fast and cost-effective means to assess the ctDNA fraction without prior knowledge of the genetic landscape of the tumor. Furthermore, mFAST-SeqS-based ctDNA levels provided an early means of measuring treatment response.

Efficacy and Safety of Vinorelbine-Capecitabine Oral Metronomic Combination in Elderly Metastatic Breast Cancer Patients: VICTOR-1 Study

2017 ◽  
Vol 103 (1) ◽  
pp. e4-e8 ◽  
Author(s):  
Marina E. Cazzaniga ◽  
Valter Torri ◽  
Francesca Riva ◽  
Luca Porcu ◽  
Federica Cicchiello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Clinical Benefit ◽  
Objective Response ◽  
Metastatic Breast ◽  
Efficacy And Safety ◽  
Breast Cancer Patients ◽  
Oral Vinorelbine ◽  
Metastatic Sites

Purpose Elderly patients with metastatic breast cancer are expected to derive similar benefits from chemotherapy as younger patients, but are more likely to experience therapy-related toxicity. Data from the VICTOR-1 study showed that metronomic therapy with vinorelbine and capecitabine was effective and well tolerated in patients with metastatic breast cancer. This analysis determined the efficacy and safety of the metronomic combination of oral vinorelbine and capecitabine in a subgroup of VICTOR-1 study patients aged ≥70 years. Methods Eighteen of the 32 patients enrolled in VICTOR-1 were aged ≥70 years. Objective response and clinical benefit rates were calculated and toxicity was determined using the NCI-CTCAE criteria. Results All patients had at least 1 comorbidity (4 had 2 comorbidities), and 77.7% were taking concomitant medication. Eight patients (44%) had received ≥1 chemotherapy regimens for metastatic disease and most (78%) had ≥2 metastatic sites. Grade 1-2 adverse events occurred in 45.8% of cycles, whereas the incidence of grade 3 and grade 4 events was very low (1.5% and 0.7%, respectively). Median time to progression was 10.5 months (range 1-40). The objective response rate was 33% and the clinical benefit rate was 67%. Conclusions The all-oral metronomic combination of vinorelbine and capecitabine had an acceptable efficacy profile and appears to be better tolerated than standard treatment schedules in elderly metastatic breast cancer patients (age ≥70 years).

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