scholarly journals Systemic immunity markers associated with lymphocytes predict the survival benefit from paclitaxel plus bevacizumab in HER2 negative advanced breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shogo Nakamoto ◽  
Masahiko Ikeda ◽  
Shinichiro Kubo ◽  
Mari Yamamoto ◽  
Tetsumasa Yamashita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Multivariable Analysis ◽  
Absolute Lymphocyte Count ◽  
Predictive Markers ◽  
Advanced Breast ◽  
Chemotherapeutic Regimen ◽  
Systemic Immunity ◽  
Lymphocyte Ratio ◽  
Lymphocyte To Monocyte Ratio

AbstractAlthough paclitaxel plus bevacizumab (PB) therapy is an effective chemotherapeutic regimen for HER2-negative advanced breast cancer (ABC), predictive markers for its effectiveness remain undefined. We investigated the usefulness of systemic immunity markers associated with lymphocytes as predictive markers for PB therapy in patients with HER2-negative ABC. We retrospectively reviewed data from 114 patients with HER2-negative ABC who underwent PB therapy from November 2011 to December 2019. We calculated the absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) as representative systemic immunity markers. The time to treatment failure (TTF) and overall survival (OS) of the patients with high ALC, low NLR, and high LMR were significantly longer compared with those of the patients with low ALC, high NLR, and low LMR. A multivariable analysis revealed that high ALC, low NLR, and low PLR were independent predictors for TTF and high ALC, low NLR, and high LMR were independent predictors for OS. Systemic immunity markers were significantly associated with longer TTF and OS in patients who underwent PB therapy and may represent predictive markers for PB therapy in patients with HER2-negative ABC.

The Systemic Immune Markers at Diagnosis Can Predict the Survival Benefit in Advanced Breast Cancer

2021 ◽  
Vol 1 (5) ◽  
pp. 471-478
Author(s):  
SHOGO NAKAMOTO ◽  
MASAHIKO IKEDA ◽  
SHINICHIRO KUBO ◽  
MARI YAMAMOTO ◽  
TETSUMASA YAMASHITA ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Prognostic Markers ◽  
Absolute Lymphocyte Count ◽  
Advanced Breast ◽  
City Hospital ◽  
Immune Markers ◽  
First Line ◽  
Lymphocyte To Monocyte Ratio ◽  
Time To Treatment Failure

Background/Aim: It has been difficult to establish prognostic markers for overall survival (OS) in patients with advanced breast cancer (ABC). Although systemic immune markers were reported as prognostic markers in several cancers, their utility in ABC remains unclear. Patients and Methods: We retrospectively analyzed 331 ABC patients, who received treatment at Fukuyama City Hospital between April 2009 and December 2020. Results: Patients with high absolute lymphocyte count (ALC), low neutrophil-to-lymphocyte ratio (NLR), and high lymphocyte-to-monocyte ratio (LMR) had significantly longer OS (p=0.025, p=0.010, and p<0.001, respectively). High ALC and high LMR were independently associated with longer OS (p=0.020 and p=0.015, respectively). High ALC was also independently associated with longer time to treatment failure (p=0.014). Conclusion: These systemic immune markers at diagnosis can predict not only a better OS but also a better TTF after first-line treatment.

The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict efficacy of CDK 4/6 inhibitors in women with hormone receptor-positive/HER2-negative advanced breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13032-e13032
Author(s):  
Emma Zattarin ◽  
Chiara Fabbroni ◽  
Francesca Ligorio ◽  
Federico Nichetti ◽  
Riccardo Lobefaro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Hormone Receptor ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
Immunomodulatory Activity ◽  
Lymphocyte Ratio ◽  
Hormone Receptor Positive ◽  
The Impact

e13032 Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors combined with endocrine therapies (ETs) are a mainstay of treatment for patients (pts) with hormone receptor-positive advanced breast cancer (HR+ aBC). Preclinical evidence indicates that their ability to stimulate antitumor immunity may crucially contribute to their anticancer activity. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) reflect systemic inflammation and immune system functional status and could be associated with CDK 4/6 inhibitor efficacy in pts with HR+ aBC. Methods: A retrospective, monocentric study was performed to investigate the association between NLR or PLR, as measured at baseline and after the first three treatment cycles, and progression free survival (PFS) in HR+ aBC pts treated with CDK 4/6 inhibitors. The thresholds for NLR and PLR were defined using the maximally selected rank statistics. Cox proportional hazard model was used to evaluate the impact of these parameters on PFS at univariate and multivariable analysis. Results: We evaluated a total number of 162 pts. Of them 142 were treated with palbociclib, 17 with ribociclib and 3 with abemaciclib plus ETs between January 2017 and December 2019 at our Institution. NLR and PLR at baseline were not associated with PFS. Conversely, high NLR ( > 3) and high PLR ( > 323.6) after three treatment cycles were associated with significantly lower PFS (p = 0.011 and p = 0.013, respectively). Multivariable analysis confirmed an independent association between high NLR or PLR and lower PFS (aHR 3.66, 95% CI 1.44-9.33, p = 0.007 and aHR 2.79, 95% CI 1.36-5.70, p = 0.005, respectively). Conclusions: To the best of our knowledge this is the first study to show a significant association between high NLR or PLR values and lower PFS in HR+ aBC pts treated with CDK 4/6 inhibitors. The association was not present with baseline values but only when NLR or PLR were measured after three treatment cycles, suggesting potential immunomodulatory activity of CDK 4/6 inhibitors.

Alpelisib and fulvestrant efficacy in HR-positive HER2-negative PIK3CA-mutant advanced breast cancer: Data from the French early access program.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1064-1064
Author(s):  
Diana Bello ◽  
Alexandre Bertucci ◽  
Thibault De La Motte Rouge ◽  
Cyriac Blonz ◽  
Sarra Akla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Advanced Breast ◽  
Prior Treatment ◽  
Cancer Data ◽  
Early Access ◽  
Systemic Treatments ◽  
Access Program

1064 Background: In 11.2018, the PIK3CA-inhibitor alpelisib was made available in France through an early access program (EAP), in combination with fulvestrant in pre-treated PIK3CA-mutant, HR-positive, HER2-negative advanced breast cancer (ABC) patients. Patients had to received two or more prior systemic treatments for ABC, including an aromatase inhibitor and a CDK4/6 inhibitor in the absence of contraindications. This retrospective real-life, EAP-based study aimed to assess the efficacy and safety of alpelisib/fulvestrant combination in the post CDK4/6 inhibitor setting. Methods: The IRB-approved protocol and call for data were sent on 10.2020 to the cancer centers which participated the most in the EAP prospective registry. Eligible patients were women who started alpelisib/fulvestrant between 11. 2018 and 10.2020 as part of the EAP (which excluded patients with visceral crisis or inflammatory BC). Alpelisib and fulvestrant were used at standard doses. Primary endpoint was PFS by local investigators using RECIST1.1. Secondary endpoints included objective response rate and safety (NCI CTCAE v5.0). Results: 10 centers provided individual data regarding 209 consecutive patients. Patients had received a median number of 4 (1-14) previous systemic treatments for ABC, including CDK4/6 inhibitors, chemotherapy, fulvestrant (alone or in combination) and everolimus for 206 (98.8%), 159 (76.1%), 163 (78%) and 123 (58.8%) patients, respectively. With a median FU of 7.0 months, median PFS was 4.0 months (95%CI [3.5;5.0]) and 35.4% of 164 evaluable patients had an objective response. After stratification on the number of prior lines of treatment, prior exposure to everolimus had no impact on PFS (mPFS in the 123 patients pretreated with everolimus: 4.0m, 95%CI [3.5-5.5]). Of note, this population was enriched in patients who had a long disease control by everolimus (median time spent on everolimus: 7.0m, range (6.5-9.0)). In multivariable analysis, characteristics significantly associated with longer PFS were PS < 3 (HR = 0.03, 95%CI [0.02-0.29]) and prior treatment with fulvestrant (HR = 0.53, 95%CI [0.32-0.89]). N = 81(38.8%) patients discontinued alpelisib due to adverse events (AEs). Most frequent grade 3/4 AEs were hyperglycemia, skin rash, diarrhea and fatigue occurring in 13.4, 8.1, 4.8 and 1.9 % of patients, respectively. Conclusions: Despite heavy pre-treatments, alpelisib +fulvestrant had a clinically relevant efficacy in the French EAP population. Interestingly, prior treatment with either everolimus or fulvestrant did not overtly impair alpelisib-fulvestrant efficacy. The best treatment sequence for PI3KCA/mTOR inhibitors could be examined in future trials in PIK3CA-mutant ER+/HER2- ABC patients.

Genomic markers of early progression on fulvestrant with or without palbociclib for ER+ advanced breast cancer in the PALOMA-3 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1010-1010 ◽  
Author(s):  
Ben O'Leary ◽  
Ros Cutts ◽  
Xin Huang ◽  
Sarah Hrebien ◽  
Yuan Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Tp53 Mutation ◽  
Dna Analysis ◽  
Multivariable Analysis ◽  
Gene Panel ◽  
Advanced Breast ◽  
Phase Iii ◽  
Tumor Purity ◽  
Early Progression

1010 Background: Markers of early progression on endocrine therapy in combination with CDK4/6 inhibitors remain limited despite the key role of these combinations in treating of ER+ advanced breast cancer (ABC). We investigated genomic aberrations in patients treated with fulvestrant, with and without palbociclib, with a circulating tumor DNA analysis of baseline plasma in the PALOMA-3 trial. Methods: PALOMA-3 was a phase III trial that randomized 521 patients with ER+/HER2- ABC 2:1 to palbociclib plus fulvestrant (P+F) or placebo plus fulvestrant (F). Using baseline plasma samples, somatic mutations were assessed with a 17 gene panel. Copy number aberrations (CNA) were characterized with a 14 gene panel including ~800 SNPs in 8 commonly altered regions for estimation of tumor purity, the percentage of plasma DNA that was derived from tumor cells. Results for mutations and CNAs were available in 310 pts (203 P+F, 107 F) and were associated with clinical characteristics and progression free survival (PFS) using univariable and multivariable Cox proportional hazards models, including tumor purity and treatment as variables. Results: In the multivariable analysis of the whole cohort, higher baseline tumor purity in plasma was associated with worse PFS (HR 1.20, 95% CI 1.09 – 1.32, p = 0.0001, HR per 10% increase in purity). Baseline TP53 mutation was also associated with shorter PFS (HR 1.84, 95%CI 1.27 – 2.65, p = 0.0011), as was baseline FGFR1 amplification (HR 2.91, 95%CI 1.61 – 5.25, p = 0.0004). PIK3CA and ESR1 mutations had no significant association with PFS in the multivariable model. Palbociclib treatment effect was comparable with the overall trial result (HR 0.43, 95%CI 0.32 - 0.57, p < 0.0001). TP53 mutations were significantly associated with visceral (q = 0.046) and soft tissue/LN metastases (q = 0.042) and the number of disease sites (q = 0.0086) after correction for multiple testing. Conclusions: TP53 mutation, FGFR1 amplification , and tumor purity in plasma identified patients at risk of early progression In PALOMA-3. If validated these results could inform future clinical trials of CDK4/6 inhibitors combinations.

Prognostic Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio in Different Phenotypes of Locally Advanced Breast Cancer During Neoadjuvant Systemic Treatment

2020 ◽  
Vol 20 (4) ◽  
pp. 307-316.e1 ◽  
Author(s):  
Wendy Muñoz-Montaño ◽  
Paula Cabrera-Galeana ◽  
Alberto Alvarado-Miranda ◽  
Cynthia Villarreal-Garza ◽  
Alejandro Mohar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Prognostic Value ◽  
Systemic Treatment ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio
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