scholarly journals Neoadjuvant Therapy of Cyclin-Dependent Kinase 4/6 Inhibitors Combined with Endocrine Therapy in HR+/HER2− Breast Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-11
Author(s):  
Kai Hong ◽  
Lingli Yao ◽  
Xianneng Sheng ◽  
Dan Ye ◽  
Yu Guo
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Endocrine Therapy ◽  
Meta Analysis ◽  
Complete Response ◽  
Cochrane Library ◽  
Cyclin Dependent Kinase ◽  
Residual Cancer Burden ◽  
Her2 Breast Cancer

<b><i>Background:</i></b> Cyclin-dependent kinase (CDK) 4/6 inhibitors have been advocated for adjuvant therapy of metastatic hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)− breast cancer (BC). However, the efficiency of adding CDK 4/6 inhibitors to neoadjuvant therapy was not unequivocal. <b><i>Objective:</i></b> The aim of the study was to evaluate the efficiency and toxicity of neoadjuvant CDK 4/6 inhibitors + endocrine therapy (ET) versus neoadjuvant endocrine monotherapy or standard neoadjuvant chemotherapy in HR+/HER2− BC. <b><i>Method:</i></b> We searched PubMed, the Cochrane Library, Web of Science, and Embase online databases for randomized controlled trials and single-arm studies written in English until April 2021. <b><i>Results:</i></b> Five studies comparing CDK 4/6 inhibitors + ET as neoadjuvant treatments to ET alone and 2 studies comparing neoadjuvant CDK 4/6 inhibitors + ET to neoadjuvant chemotherapy were analysed. Neoadjuvant CDK 4/6 inhibitors + ET improved the rate of complete cell cycle arrest (CCCA: central Ki67 &#x3c; 2.7%, odds ratio [OR] = 7.91, 95% confidence interval [CI] = 4.81–13.03, <i>p</i> &#x3c; 0.001), increased the risk of adverse events (AEs; especially ≥3 AEs; AEs of all grades: OR = 9.10, 95% CI = 2.39–34.58, <i>p</i> = 0.001; AEs ≥3: OR = 12.24, 95% CI = 4.17–35.88, <i>p</i> &#x3c; 0.001), led to no significant differences in pathological complete response (pCR) in patients with BC (OR = 0.34, 95% CI = 0.04–2.85, <i>p</i> = 0.318) compared to endocrine monotherapy. Moreover, subgroup analysis showed that the 3 types of CDK 4/6 inhibitors all improved the rate of CCCA (ribociclib: OR = 10.31, 95% CI = 3.59–29.61, <i>p</i> &#x3c; 0.001; palbociclib: OR = 7.39, 95% CI = 1.26–43.40, <i>p</i> = 0.027, and abemaciclib: OR = 8.28, 95% CI = 3.41–20.11, <i>p</i> &#x3c; 0.001). Compared to neoadjuvant chemotherapy, neoadjuvant CDK 4/6 inhibitors plus ET decreased the risk of AEs ≥3 (OR = 0.50, 95% CI = 0.29–0.87, <i>p</i> = 0.015) and showed similar ability to reach pCR (OR = 0.50, 95% CI = 0.12–2.07, <i>p</i> = 0.342) and reduce the residual cancer burden (RCB, RCB 0–1: OR = 0.47, 95% CI = 0.18–1.22, <i>p</i> = 0.121; RCB 2–3: OR = 2.30, 95% CI = 0.89–5.91, <i>p</i> = 0.084). <b><i>Conclusions:</i></b> The results suggested that combination therapy had increased efficacy and toxicity compared to endocrine monotherapy and showed similar efficacy to and better safety than neoadjuvant chemotherapy.

Multi-gene prognostic assays and age-related differences in prediction of pathologic complete response to neoadjuvant chemotherapy and survival in breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 591-591
Author(s):  
Kent Hanson ◽  
Kent Hoskins ◽  
Naomi Yu Ko ◽  
Gregory Sampang Calip
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Genomic Testing ◽  
Younger Women ◽  
Her2 Breast Cancer ◽  
Response To Neoadjuvant Chemotherapy ◽  
Overall Mortality

591 Background: Multi-gene testing of primary breast tumors in early-stage breast cancer is used to classify the risk of developing distant metastases and predict the benefit of adjuvant chemotherapy. The association between the tumor genomic prognostic score (GPS) and response to neoadjuvant chemotherapy (NACT) and survival is not well characterized. Our objective was to describe the association between GPS and rates of pathologic complete response (PCR) and subsequent overall survival among women with or without PCR. Methods: We utilized the National Cancer Database to perform a hospital-based, retrospective cohort study of breast cancer patients ages 18 years and older. We included women diagnosed with first primary stages I-III hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer who received NACT and surgery between 2010 and 2017. Women were categorized as having low (0-10 or 200), intermediate (11-25 or 300), or high-risk (25-199 or 400) GPS based on OncotypeDX or MammaPrint scores. Multivariable modified Poisson regression models with robust error variance were used to estimate the crude and adjusted relative risk and 95% confidence intervals (CI) for PCR associated with GPS groups. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) and 95% CI for associations between the GPS and overall survival (OS) in women who did and did not have PCR. Results: A cohort of 3,446 women (mean [SD] age, 56.7 [12.0] years; median [interquartile range] follow-up of 47 [31-68] months) who received genomic testing and neoadjuvant chemotherapy were included in our analysis, of which 935 (27%) were low risk, 1,357 (39%) intermediate risk, and 1,154 (34%) high risk GPS. The relative risk of PCR for all women with high GPS was 1.81 (95% CI, 1.47-2.22; p < 0.001) in crude models and 1.49 (95% CI, 1.16-1.92; p = 0.002) after full adjustment compared to low GPS. Across all models, having a high GPS was significantly associated with achieving PCR in younger women ( < 65 years). In women ages ≥65 years, the association between GPS and PCR was not predictive nor statistically significantly. Among women with no response or partial response to NACT, high GPS was associated with a significantly increased risk of overall mortality (HR 2.41; 95% CI, 1.61-3.60; p < 0.001) compared to low GPS. Conversely, in women who did achieve PCR, GPS was not predictive of overall mortality across all age groups. Conclusions: In women with HR+/HER2- breast cancer, high risk GPS was predictive of PCR following NACT, primarily in younger women ( < 65 years). Our findings also indicated GPS was associated with lower OS in high-risk patients who do not achieve PCR and unpredictive of OS in those without PCR. The utility of tumor genomic testing in the neoadjuvant setting needs further investigation.

scholarly journals Platinum-based neoadjuvant chemotherapy for triple-negative breast cancer: a systematic review and meta-analysis

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096434
Author(s):  
Zhen-Yu Li ◽  
Zhen Zhang ◽  
Xiao-Zhong Cao ◽  
Yun Feng ◽  
Sha-Sha Ren
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Meta Analysis ◽  
Complete Response ◽  
Extensive Literature ◽  
Extensive Literature Search ◽  
Positive Breast Cancer

Background Triple-negative breast cancer (TNBC) is associated with higher aggressiveness and mortality than hormone-positive breast cancer because of the lack of approved therapeutic targets. Patients with TNBC who attain a pathological complete response (pCR) after neoadjuvant chemotherapy have improved survival. Platinum-based agents show promising activity in TNBC; however, their use remains controversial. We conducted a meta-analysis to assess the role of platinum-based agents in neoadjuvant chemotherapy in patients with TNBC. Methods We performed an extensive literature search of the Pubmed, Embase, and Cochrane databases. We calculated pooled odds ratios (OR) with 95% confidence intervals (CI) for the identified studies. Results Eight randomized controlled trials with 1345 patients were included in the analysis. The addition of platinum-based agents improved pCR compared with neoadjuvant therapy based on anthracyclines, cyclophosphamide, taxanes, and fluorouracil (49.1% vs. 35.9%; OR: 1.87, 95% CI: 1.23–2.86). Hematological adverse events were similar in both groups, except for more thrombocytopenia in the platinum-based group (OR: 7.96, 95% CI: 3.18–19.93). Conclusion The addition of platinum-based agents to neoadjuvant chemotherapy improved pCR rates in patients with TNBC, with a slight increase in hematological toxicities. Platinum-based agents might thus be an accessible and economically viable option in patients with TNBC.

A meta-analysis of platinum-based neoadjuvant chemotherapy versus standard neoadjuvant chemotherapy for triple-negative breast cancer

2019 ◽  
Vol 15 (23) ◽  
pp. 2779-2790 ◽  
Author(s):  
Dong Wang ◽  
Jiafu Feng ◽  
Bei Xu
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Randomized Clinical Trials ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Meta Analysis ◽  
Complete Response ◽  
Breast Cancers ◽  
Dna Damaging Agents ◽  
Platinum Agents

Aim: Platinum agents are DNA damaging agents with promising activity in breast cancers, especially in triple-negative subgroup. This meta-analysis was conducted to compare the treatments of platinum-based neoadjuvant chemotherapy (NAC) and standard NAC for triple-negative breast cancers (TNBCs). Materials & methods: Diverse electronic databases were searched to identify the randomized clinical trials that directly compared the treatments of platinum-based NAC versus NAC in TNBC patients. Toxicity of platinum-based regimens was further evaluated. Results: Addition of platinum agents significantly improved the pathological complete response rates in TNBC patients compared with the standard NAC. Unfortunately, platinum-based regimens were more likely to develop higher incidence of hematologic toxicities. Conclusion: Platinum-based NAC regimens could achieve significant pathological complete response improvement with well-tolerated toxicity in TNBC patients.

Neoadjuvant chemotherapy regimens for triple-negative breast cancer: Insights from network meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12635-e12635
Author(s):  
Hirotaka Miyashita ◽  
Christina Cruz ◽  
Stephen C. Malamud
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Gastrointestinal Complications ◽  
Therapy Regimen ◽  
Neoadjuvant Systemic Therapy ◽  
Grade 3

e12635 Background: The best regimen for neoadjuvant chemotherapy for triple-negative breast cancer (TNBC) is unknown. Recent studies have shown promising data that adding carboplatin improves the rate of pathological complete response (pCR) in TNBC). Therefore, we performed a network meta-analysis to define the overall most effective neoadjuvant systemic therapy for TNBC. Methods: We searched MEDLINE, Cochrane Library, and EMBASE from inception to December 2019 for studies comparing the efficacy of different neoadjuvant regimens in patients with TNBC. We performed a network meta-analysis comparing the regimens in the selected studies using the random-effects model. We focused on anthracycline (A), bevacizumab (B), everolimus (E), and platinum salts (Pl) because these are the medications commonly added to taxane based regimens. All studies contained a taxane regimen. We analyzed the rate of pCR (ypT0/is, N0) and the incidence of grade 3-4 neutropenia, thrombocytopenia, nausea/vomiting, and diarrhea. Results: We identified a total of 13 randomized control trials for this analysis. We compared eight different classes of regimens. We found that regimens containing Pl were significantly superior to Pl non-containing regimens for the rate of pCR. (risk ratio (RR) for pCR [95% confidence interval (CI)]: 1.66 [1.19-2.31], 1.37 [1.14-1.64], and 1.36 [1.14-1.62] for no medications of special interest vs Pl, A vs A+Pl, and A+B vs A+B+Pl, respectively). Regimens containing B were associated with a significantly better rate of pCR. (RR for pCR [95% CI]: 1.24 [1.06-1.46] and 1.23 [1.01-1.51] for A vs A+B and A+Pl vs A+B+Pl, respectively) In contrast, adding A into the regimen did not improve the rate of pCR. In the safety analysis, regimens containing Pl were associated with a significantly higher incidence of grade 3-4 neutropenia and thrombocytopenia. Regimens containing B showed a higher incidence of grade 3-4 nausea/vomiting, and diarrhea. Conclusions: For TNBC, adding Pl or B into the neoadjuvant therapy regimen brings about a higher pCR rate, though they are associated with an increase in hematologic or gastrointestinal complications. The benefit of adding A to the neoadjuvant chemotherapy regimen for TNBC is not apparent.

Locoregional recurrence following pathologic complete response in patients with T1-3 N0 breast cancer treated with neoadjuvant chemotherapy, breast conserving surgery and whole breast radiation: Is a trial of omission of radiation warranted?

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12625-e12625
Author(s):  
Elena Parvez ◽  
Thierry Muanza
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Locoregional Recurrence ◽  
Prospective Trial ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Breast Conserving Surgery ◽  
Study Objective

e12625 Background: Pathologic complete response(pCR) after neoadjuvant chemotherapy(NAC) in patients with breast cancer(BC) is associated with decreased recurrence and improved survival. In NSABP B18 and B27, 10-yr locoregional recurrence(LRR) after pCR in patients with Stage I-III BC undergoing breast conserving surgery(BCS) and whole breast RT(WBRT) was 5.2-6.9%. However, LRR may be overestimated as Her2 therapy was not used and only some eligible patients received endocrine therapy. A retrospective study using modern protocols found a 5-yr LRR of up to 2.6%. We hypothesize that LRR in N0 patients is even lower, and de-escalation of therapy should be examined. The study objective is to assess if a prospective trial of omission of WBRT after BCS in patients with N0 BC and pCR after NAC is warranted and to assess feasibility. Methods: Patients with T1-T3 N0 invasive BC diagnosed between Dec 2011-2017 treated with NAC and BCS were identified from a hospital BC registry. Health records were retrospectively reviewed to identify patients with pCR, defined as absence of residual invasive or in-situ disease(ypT0N0). Incidents of locoregional and distant recurrence were recorded. Results: Of 89 patients with T1-3 N0 invasive BC treated with NAC and BCS, 29(32.6%) had pCR. Median follow-up was 61.1 months. Median age was 55 yrs and median tumour size was 2.4cm. Receptor status was 16(55.2%) HR-Her2-, 4(13.8%) HR-Her2+, 7(24.1%) HR+Her2+ and 2(6.9%) HR+Her2-. NAC protocols consisted of an anthracycline and/or a taxane in 27(90%) patients, and 6 patients were treated on NAC trials. All patients with Her2+ disease received Her2 targeted therapy. Adjuvant endocrine therapy was taken by 8 of 9 patients with HR+ disease. All patients received WBRT without nodal RT. RT plan was available for 26(86.7%) patients. RT dose ranged from 40-50Gy, and all but 4 received tumour bed boost. There were no local or regional recurrence events at last follow-up. One patient developed brain metastases at 15.7 months. Conclusions: Over 6 years, 29 patients were identified that would be eligible for a prospective trial evaluating omission of WBRT after pCR in N0 patients treated with NAC and BCS. At median 5-yr follow-up, there were no locoregional recurrences in our cohort, demonstrating that the absolute benefit provided by WBRT is likely small. Our results indicate a prospective trial is warranted and will require multi-institution participation to accrue.

Docetaxel and cyclophosphamide as neoadjuvant chemotherapy in ER+ HER2- breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 590-590
Author(s):  
Hiroshi Yagata ◽  
Hideko Yamauchi ◽  
Atsushi Yoshida ◽  
Naoki Hayashi ◽  
Yuka Kajiura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Clinical Response ◽  
Complete Response ◽  
Operable Breast Cancer ◽  
Nuclear Grade ◽  
Standard Regimen ◽  
Her2 Breast Cancer ◽  
Grade 3 ◽  
Mib 1

590 Background: Recently, docetaxel plus cyclophosphamide (TC) has been established as a standard regimen for adjuvant chemotherapy in operable breast cancer. However, the efficacy of TC as neoadjuvant chemotherapy remains unclear, especially in hormone-responsive breast cancer. We prospectively evaluated the response to TC neoadjuvant chemotherapy in patients with ER+ HER2- operable breast cancer. Methods: Eligible patients had ER+ and HER2- invasive breast cancer that measured more than 2 cm in diameter or was node-positive clinically between March 2009 and February 2011. Four cycles of TC (75 and 600 mg/m2) were administered intravenously every 3 weeks as neoadjuvant chemotherapy, followed by breast and axillary surgery. We investigated the clinical response on MRI and the pathological complete response (pCR) of primary invasive breast tumors. Results: We enrolled 43 patients in 45 lesions. Allred score of ER was 7 to 8 in 40 lesions, 6 in 3 lesions and 4 in 2 lesions. PgR was 7 to 8 in 31 lesions, 5 to 6 in 6 lesions, 3 to 4 in 5 lesions, and 0 in 3 lesions. Nuclear grade was 1 in 31 lesions, 2 in 7 lesions, and 3 in 7 lesions. MIB-1 index was median 22% (range, 6 to 71%) in 40 measurable lesions. Clinical response (CR and PR) was observed in 33 lesions (73%) and SD in 12 lesions without any lesions of clinical PD. pCR was achieved in only 1 lesions (ER 8, PgR 3, Nuclear grade 3, MIB-1 index 32.6%). Conclusions: Neoadjuvant TC produced a good clinical response in ER+ HER2- operable breast cancer, while the pCR rate was very low, regardless of the characteristics of cancer cells. Therefore, pCR is not an appropriate prognostic factor in women with ER+ HER2- operable breast cancer who receive neoadjuvant TC. Whether clinical response is related to survival should be addressed in future studies. The efficacy of neoadjuvant TC in ER+ HER2- operable breast cancer is very limited, and more effective regimens are needed to achieve higher pCR rates.

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