scholarly journals Efficacy and Safety of Anti-PD-1/ PD-L1 Monotherapy for Metastatic Breast Cancer: Clinical Evidence

2021 ◽  
Vol 12 ◽  
Author(s):  
Yihang Qi ◽  
Lin Zhang ◽  
Zhongzhao Wang ◽  
Xiangyi Kong ◽  
Jie Zhai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Rate ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Global Analysis ◽  
Objective Response ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Breast Cancer Patients

Background: Success has been reported in PD-1/PD-L1 blockade via pembrolizumab, atezolizumab, or avelumab monotherapy in manifold malignancies including metastatic breast cancer. Due to lack of large-scale study, here we present interim analyses to evaluate the safety and efficacy of these promising strategies in patients with advanced breast cancer.Methods: Six studies including 586 advanced breast cancer patients treated with anti-PD-1/PD-L1 monotherapy agents before July 1, 2020, were included. The anti-PD-1/PD-L1 agents include pembrolizumab, atezolizumab, land avelumab. Statistics was analyzed by R software and IBM SPSS Statistics 22.Results: Global analysis showed that for this monotherapy, the complete response was 1.26%, partial response was 7.65%, objective response rate (ORR) was 9.85%, and disease control rate (DCR) was 18.33%. 1-year overall survival rate and 6-month progression-free survival rate were 43.34 and 17.24%. Overall incidence of adverse events (AEs) was 64.18% in any grade and 12.94% in severe grade, while the incidence of immune-related AEs (irAEs) was approximately 14.75%: the most common treatment-related AEs of any grade that occurred in at least 5% of patients were arthralgia and asthenia; the most common severe treatment-related AEs occurred in at least 1% of patients were anemia and autoimmune hepatitis; the most common irAEs were hypothyroidism. Besides, the incidence of discontinue and death due to treatment-related AEs was about 3.06 and 0.31%, respectively. Additionally, by comparing efficacy indicators between PD-L1–positive and PD-L1–negative groups, an implicated correspondence between efficacy and the expression of PD-L1 biomarker was found: the PR was 9.93 vs 2.69%; the ORR was 10.62 vs. 3.07%; the DCR was 17.95 vs. 4.71%.Conclusion: Anti–PD-1/PD-L1 monotherapy showed a manageable safety profile and had a promising and durable anti-tumor efficacy in metastatic breast cancer patients. Higher PD-L1 expression may be closely correlated to a better clinical efficacy.

scholarly journals Pembrolizumab Plus Gemcitabine in the Subset of Triple-Negative Advanced Breast Cancer Patients in the GEICAM/2015-04 (PANGEA-Breast) Study

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5432
Author(s):  
Luis de la Cruz-Merino ◽  
María Gion ◽  
Josefina Cruz-Jurado ◽  
Vanesa Quiroga ◽  
Raquel Andrés ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Treatment Efficacy ◽  
Triple Negative ◽  
Objective Response ◽  
Suppressor Cells ◽  
Primary Objective ◽  
Advanced Breast ◽  
Breast Cancer Patients

The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon’s design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months.

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.

Plasma PIK3CA Mutation Testing in Advanced Breast Cancer Patients for Personalized Medicine: A Value Proposition

2020 ◽  
Vol 5 (5) ◽  
pp. 1076-1089
Author(s):  
Andrea Ferreira-Gonzalez
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Pik3ca Mutation ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Value Proposition ◽  
Breast Cancer Patients ◽  
A Value

Abstract Background Even though endocrine therapy is often initially successful in treating advanced breast cancer, most patients inevitably face disease progression. In advanced hormone receptor–positive (HR+) breast cancer, activation of the PI3K downstream pathway is a critical feature of the mechanism of endocrine resistance. A significant recent advance in treating HR+ advanced breast cancer has been the recent introduction of PI3K inhibitor (PI3Ki) for the treatment of patients with HR+, HER2-negative (HER2−) advanced or metastatic breast cancer that harbors PIK3CA mutations. A value proposition concept was applied to assess the potential benefits of cell-free tumor DNA (ctDNA) testing to identify patients who might respond to PI3Ki treatment. Content By applying the framework of the value proposition to >35 publications, in addition to recommendations from professional organizations, it was evident that robust clinical evidence exists to support the role of ctDNA PIK3CA mutation evaluation in identifying patients with advanced breast cancer who could benefit from PI3Ki treatment. Summary Detection of PIK3CA gene mutations in HR+HER2− advanced breast cancer patients allows for the identification of patients who might benefit from more effective personalized treatment with molecularly targeted drugs.

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.

scholarly journals Elevated plasma levels of TGF-beta1 in patients with locally advanced breast cancer related to other clinical stages

2003 ◽  
Vol 11 (3) ◽  
pp. 131-133 ◽  
Author(s):  
Natasa Todorovic-Rakovic ◽  
Vesna Ivanovic ◽  
Miroslav Demajo ◽  
Zora Neskovic-Konstantinovic ◽  
Dragica Nikolic-Vukosavljevic
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Disease Course ◽  
Breast Cancer Patients ◽  
Healthy Donors

Background: The application of plasma tumor markers is mainly during the follow-up of cancer patients and especially in monitoring of advanced disease. These biomarkers do not require surgical intervention and provide relatively simple monitoring at any time during the disease course. TGF-beta1 is a pluripotent cytokine, with diverse effects in normal physiology and a role in both normal mammary gland development and progression of breast cancer. In early stages of breast carcinomas TGF-beta1 acts as tumor suppressor, while in later stages, when tumor cells become resistant to growth inhibition by TGF-beta1, it acts as tumor promoter. For that reason, the aim of this study was to assess the stage-related TGF-beta1 elevation in circulation of breast cancer patients, during disease progression. Methods: We analyzed 52 breast cancer patients of different stages (I/II, III, IV) and 36 healthy donors. TGF-beta1 levels were determined by enzyme-linked immunosorbent assay (ELISA, R&D). Results Although there was no increase in plasma TGF-beta1 in stage I/II patients (n =10, median value = 0.89 ng/ml), statistically significant elevation of plasma TGF-beta1 was found in locally advanced breast cancer (stage III, n = 9, median value = 2.30 ng/ml) and also in metastatic breast cancer (stage IV, n = 33, median value = 2.46 ng/ml) in relation to healthy donors and stage I/II. Conclusion: This elevation of plasma TGF-beta1 in locally advanced breast cancer is probably the result of increased tumor mass and tumor-stromal interactions in this stage, as well as a possible cause of greater metastatic potential of tumor cells which lead to metastatic breast cancer. Prognostic role of TGF-beta1 is not fully understood, but from these results we could say that it could be a marker for monitoring patients disease course, as well as for understating the biology of breast cancer.

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).

Nanoparticle albumin-bound paclitaxel/liposomal-encapsulated doxorubicin in HER2-negative metastatic breast cancer patients

2020 ◽  
Author(s):  
Alessandra Fabi ◽  
Gianluigi Ferretti ◽  
Paola Malaguti ◽  
Simona Gasparro ◽  
Cecilia Nisticò ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Objective Response ◽  
Metastatic Breast ◽  
Maximum Tolerated Dose ◽  
Breast Cancer Patients ◽  
Primary Endpoints ◽  
Metastatic Sites ◽  
Mild Toxicity

Aim: To investigate the toxicity of nab-paclitaxel (wNP)/nonpegylated liposome-encapsulated doxorubicin (wNPLD) combination in HER2-negative metastatic breast cancer (MBC) patients as first-line treatment. Materials & methods: Phase I, single-arm study in metastatic breast cancer patients naive to previous chemotherapy for advanced disease. A 3 + 3 dose-escalation design was used to determine the safety. Primary endpoints were the identification of dose-limiting toxicity and maximum tolerated dose. Results: In total, 12 patients (mean age: 52 years; median metastatic sites: 2) were enrolled and 97 cycles were completed. Maximum tolerated dose was wNP + wNPLD 25 mg/m2. The most common adverse events were neutropenia, nausea, diarrhea and mucositis. The objective response rate was 68% (response mean duration: 12.6 months). Conclusion: wNP/wNPLD combination constitutes an active regimen with mild toxicity.

scholarly journals NGlycolylGM3/VSSP Vaccine in Metastatic Breast Cancer Patients: Results of Phase I/IIa Clinical Trial

2012 ◽  
Vol 6 ◽  
pp. BCBCR.S8488
Author(s):  
Ana de la Torre ◽  
Julio Hernandez ◽  
Ramón Ortiz ◽  
Meylán Cepeda ◽  
Kirenia Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Cancer Patients ◽  
Objective Response ◽  
Metastatic Breast ◽  
Treatment Schedule ◽  
Breast Cancer Patients

Patients treated with vaccines based on NGlycolil gangliosides have showed benefit in progression free survival and overall survival. These molecules, which have been observed in breast cancer cells, are minimally or not expressed in normal human tissue and have been considered as antigen tumor-specific. For this reason they are very attractive to immunotherapy. A phase I/II clinical trial was carried out in metastatic breast cancer patients with the NGlycolylGM3/VSSP vaccine administered by subcutaneous route. Selecting the optimal biological doses of the vaccine in these patients was the principal objective based on the immunogenicity, efficacy and safety results. Six levels of doses of vaccine were studied. Treatment schedule consisted of five doses every two weeks and then monthly until reaching a fifteenth doses. Doses levels studied were 150, 300, 600, 900, 1200 and 1500 μg. Five patients in each level were included except at the 900 μg dose, in which ten patients were included. Immunogenicity was determined by levels of antibodies generated in patients after vaccination. The response criteria of evaluation in solid tumors (RECIST) was used to evaluate antitumoral effect. Safety was evaluated by Common Toxicity Criteria of Adverse Event (CTCAE). The vaccine administration was safe and immunogenic in all does levels. Most frequent adverse events related to vaccination were mild or moderate and were related to injection site reactions and “flu-like” symptoms. Vaccination induced specific anti-NeuGcGM3 IgM and IgG antibodies responses in all patients. Disease control (objective response or stable disease) was obtained in 72.7% of evaluated patients. Median overall survival was 15.9 months. Two patients of two different dose levels achieved overall survival values of about six years. The dose of 900 μg was selected as biological optimal dose in which overall survival was 28.5 months.

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