A population model to predict progression free survival in breast cancer patients treated with neoadjuvant chemotherapy ñ vaccines based on tumour growth inhibition metrics.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12114-e12114
Author(s):  
Belen P.Solans ◽  
Diego Salas ◽  
Marta Abengozar ◽  
Luis Javier Pina ◽  
Arlette Elizalde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Neoadjuvant Therapy ◽  
Tumor Size ◽  
Clinical Benefit ◽  
Progression Free Survival ◽  
Free Survival

e12114 Background: Breast cancer (BC) is the most commonly diagnosed malignancy in women. Neoadjuvant chemotherapy selects patients with optimal pathological responses and increases tumorectomy versus total mastectomy. Changes in tumor size (CTS) are related to an early clinical benefit and to Progression Free Survival (PFS) and Overall Survival (OS) in BC patients. Thus, the identification of new prognostic factors in the neoadjuvant scenario is crucial. Objectives:To assess the link between tumor growth inhibition metrics (TGI) and progression free survival (PFS) based on data obtained from BC patients with neoadjuvant therapy Methods: Data were obtained from 218 patients with BC treated at the University Clinic of Navarra, diagnosed from January 2008 to February 2016, with a median age of 49 years (range 25 to 84). Classification of molecular subtypes was based on IHC and found as follows: Her2 (6%), LA ( 23%), LB ( 36%), LB-Her2 (10%) and TN ( 25%). Patients were treated with ddECx 4 followed Docetaxel x 4. Her2 patients had therapy with Trastuzumab. 18% of the patients (LB and TN) received vaccination with dendritic cells. Data were analysed under the population approach with NONMEN 7.3. A model accounting for the dynamics of tumor growth and antitumor effect of the neoadjuvant therapy was developed. The model describes tumor size as the sum of the longest diameters of target lesions as a function of time and drug exposure. A PFS model was developed to describe the PFS time distribution as a function of covariates Results: The TGI was able to individually and accurately describe the tumor shrinkage. Vaccinated patients had an increased shrinkage rate of 36% (p < 0.001) than those who were not (p < 0.001). PFS (months) was best described by a Weibull model, and greater tumor size at diagnosis (p < 0.05), smaller CTS (p < 0.05) and TN subtype (p < 0.001) were identified as poor prognostic factors Conclusions: A PFS model that uses a model-based estimate of tumor growth to predict the PFS of BC patients receiving neoadjuvant therapy has been developed. This model helps to gain early understanding of potential clinical benefit to facilitate go/no-go decision making.

scholarly journals Single arm, phase two study of low-dose metronomic eribulin in metastatic breast cancer

2021 ◽  
Author(s):  
Pavani Chalasani ◽  
Kiah Farr ◽  
Vicky Wu ◽  
Isaac Jenkins ◽  
Alex Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Peripheral Neuropathy ◽  
Clinical Benefit ◽  
Low Dose ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival

Abstract Background Treatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician’s choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile. Methods We conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m2 administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy. Findings We consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients. Interpretation Metronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.

Association of non-disruptive P53 mutations with poor progression-free survival (PFS) in resected breast cancer treated with neoadjuvant chemotherapy.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 1042-1042
Author(s):  
Alejandro Martinez-Bueno ◽  
Sonia Baulies ◽  
Miguel Angel Molina-Vila ◽  
Jordi Bertran-Alamillo ◽  
Maria Gonzalez Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Progression Free Survival ◽  
P53 Mutations ◽  
Free Survival

Prognostic Factors Influencing Progression-Free Survival Determined From a Series of Sporadic Desmoid Tumors: A Wait-and-See Policy According to Tumor Presentation

2011 ◽  
Vol 29 (26) ◽  
pp. 3553-3558 ◽  
Author(s):  
Sébastien Salas ◽  
Armelle Dufresne ◽  
Binh Bui ◽  
Jean-Yves Blay ◽  
Philippe Terrier ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Tumor Size ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Surgical Margins ◽  
Desmoid Tumors ◽  
Tumor Site ◽  
Free Survival ◽  
Wait And See

Purpose Desmoid tumors are mesenchymal fibroblastic/myofibroblastic proliferations with locoregional aggressiveness and high ability to recur after initial treatment. We present the results of the largest series of sporadic desmoid tumors ever published to determine the prognostic factors of these rare tumors. Patients and Methods Four hundred twenty-six patients with a desmoid tumor at diagnosis were included, and the following parameters were studied: age, sex, delay between first symptoms and diagnosis, tumor size, tumor site, previous history of surgery or trauma in the area of the primary tumor, surgical margins, and context of abdominal wall desmoids in women of child-bearing age during or shortly after pregnancy. We performed univariate and multivariate analysis for progression-free survival (PFS). Results In univariate analysis, age, tumor size, tumor site, and surgical margins (R2 v R0/R1) had a significant impact on PFS. PFS curves were not significantly different for microscopic assessment of surgical resection quality (R0 v R1). In multivariate analysis, age, tumor size, and tumor site had independent values. Three prognostic groups for PFS were defined on the basis of the number of independent unfavorable prognostic factors (0 or 1, 2, and 3). Conclusion This study clearly demonstrates that there are different prognostic subgroups of desmoid tumors that could benefit from different therapeutic strategies, including a wait-and-see policy.

Conditional survival of patients with nonmetastatic bone osteosarcoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23511-e23511
Author(s):  
Ruoyu Miao ◽  
Haotong Wang ◽  
Edwin Choy ◽  
Gregory Michael Cote ◽  
Kevin Raskin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Survival Time ◽  
Disease Progression ◽  
Tumor Size ◽  
Resection Margin ◽  
Progression Free Survival ◽  
Conditional Survival ◽  
Histologic Subtype ◽  
Free Survival

e23511 Background: Conditional survival provides a dynamic prediction of prognosis for patients surviving a defined period of time after diagnosis. This study aimed to determine the conditional survival and prognostic factors over time among patients with non-metastatic bone osteosarcoma. Methods: We reviewed 714 bone osteosarcoma patients treated from 1985 to 2016. Patients with metastatic disease at diagnosis or limited follow up were excluded, resulting in 587 cases for analysis. Clinical and pathological variables were recorded. Predictive variables included age at diagnosis, gender, previous radiation history, tumor site, tumor size, histologic subtype, histologic grade, resection margin, chemotherapy, and radiation therapy. The multivariate Cox proportional hazards regression was used to analyze prognostic factors of conditional overall survival and progression-free survival at baseline and 5 years after diagnosis. Results: The estimated 5-year conditional overall survival increased from 71.0% (95% CI: 67.5%-75.0%) at baseline to 86.9% (95% CI: 82.6%-90.5%) at 5 years, which means if a patient with non-metastatic bone osteosarcoma survived 5 years, the chance of surviving another 5 years was 86.9%. If the patient was progression-free for 5 years, the 5-year conditional overall survival was even higher, 93.2% (95% CI: 89.5%-96.4%), and the 5-year conditional progression-free survival improved from 57.1% (95% CI: 53.3%-61.0%) at baseline to 91.2% (95% CI: 87.5%-94.6%) at 5 years. Prognostic factors for mortality and disease progression change as survival time increases. At baseline, age (p < 0.001 and p = 0.003), histologic subtype (p < 0.001 and p = 0.001), grade (p < 0.001 and p < 0.001), tumor size (p = 0.002 and p = 0.002), resection margin (p < 0.001 and p < 0.001) and chemotherapy (p = 0.001 and p = 0.001) were predictive of both overall survival and progression-free survival. However, only age (p < 0.001) and histologic subtype (p = 0.015) remained significant for mortality and resection margin (p = 0.001) for disease progression at 5 years. Conclusions: The survival probability of osteosarcoma improves as survival time increases. Estimates of conditional survival can provide useful information for individualized surveillance strategies, risk evaluation, patient counseling, and making clinical decisions.

scholarly journals Association of PTP1B with Outcomes of Breast Cancer Patients who Underwent Neoadjuvant Chemotherapy

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S40934 ◽  
Author(s):  
Monica M. Rivera Franco ◽  
Eucario Leon Rodriguez ◽  
Braulio Martinez Benitez ◽  
Luisa G. Villanueva Rodriguez ◽  
Maria De La Luz Sevilla Gonzalez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Limited Sample ◽  
Free Survival ◽  
Epidermal Growth

PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR). Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5%) and overexpression (≥5%). Patients' responses were graded according to the Miller-Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR (P = 0.2). However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens (P = 0.02). Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B overexpression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded.

scholarly journals A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1148 ◽  
Author(s):  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Li Yan ◽  
John M.L. Ebos ◽  
Omar M. Rashid ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Marker Genes ◽  
Gene Score ◽  
Primary Tumors ◽  
Predictive Values ◽  
Free Survival ◽  
Response To Neoadjuvant Chemotherapy

We generated a 4-gene score with genes upregulated in LM2-4, a metastatic variant of MDA-MB-231 (DOK 4, HCCS, PGF, and SHCBP1) that was strongly associated with disease-free survival (DFS) in TCGA cohort (hazard ratio [HR]>1.2, p < 0.02). The 4-gene score correlated with overall survival of TCGA (HR = 1.44, p < 0.001), which was validated with DFS and disease-specific survival of METABRIC cohort. The 4-gene score was able to predict worse survival or clinically aggressive tumors, such as high Nottingham pathological grade and advanced cancer staging. High score was associated with worse survival in the hormonal receptor (HR)-positive/Her2-negative subtype. High score enriched cell proliferation-related gene sets in GSEA. The score was high in primary tumors that originated, in and metastasized to, brain and lung, and it predicted worse progression-free survival for metastatic tumors. Good tumor response to neoadjuvant chemotherapy or hormonal therapy was accompanied by score reduction. High scores were also predictive of response to neoadjuvant chemotherapy for HR-positive/Her2-negative subtype. High score tumors had increased expression of T cell exhaustion marker genes, suggesting that the score may also be a biomarker for immunotherapy response. Our novel 4-gene score with both prognostic and predictive values may, therefore, be clinically useful particularly in HR-positive breast cancer.

scholarly journals Celecoxib With Neoadjuvant Chemotherapy for Breast Cancer Might Worsen Outcomes Differentially by COX-2 Expression and ER Status: Exploratory Analysis of the REMAGUS02 Trial

2019 ◽  
Vol 37 (8) ◽  
pp. 624-635 ◽  
Author(s):  
Anne-Sophie Hamy ◽  
Sandrine Tury ◽  
Xiaofei Wang ◽  
Junheng Gao ◽  
Jean-Yves Pierga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cell Lines ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Breast Cancer Cell Lines ◽  
Free Survival ◽  
Distant Relapse ◽  
Cox 2 ◽  
Group B

PURPOSE The overexpression of cyclooxygenase 2 (COX-2) gene, also known as prostaglandin-endoperoxide synthase 2 ( PTGS2), occurs in breast cancer, but whether it affects response to anticox drugs remains unclear. We investigated the relationships between PTGS2 expression, celecoxib use during neoadjuvant chemotherapy (NAC), and both event-free survival (EFS) and overall survival (OS). MATERIALS AND METHODS We analyzed a cohort of 156 patients with human epidermal growth factor receptor 2 –negative breast cancer from the REMAGUS02 (ISRCTN Registry No. 10059974) trial with pretreatment PTGS2 expression data. Patients were treated by sequential NAC (epirubicin plus cyclophosphamide followed by docetaxel with or without celecoxib). Experimental validation was performed on breast cancer cell lines. The Cancer and Leukemia Group B (CALGB) 30801 ( ClinicalTrials.gov identifier: NCT01041781) trial that tested chemotherapy with or without celecoxib in patients with lung cancer served as an independent validation cohort. RESULTS After 94.5 months of follow-up, EFS was significantly lower in the celecoxib group (hazard ratio [HR], 1.7; 95% CI, 1 to 2.88; P = .046). A significant interaction between PTGS2 expression and celecoxib use was detected ( Pinteraction = .01). In the PTGS2-low group (n = 100), EFS was lower in the celecoxib arm (HR, 3.01; 95% CI, 1.45 to 6.24; P = .002) than in the standard treatment arm. Celecoxib use was an independent predictor of poor EFS, distant relapse–free survival, and OS. Celecoxib in addition to docetaxel enhanced cell viability in PTGS2-low cell lines but not in PTGS2-high cell lines. In CALGB 30801, a trend toward poorer progression-free survival was observed in the patients with low urinary metabolite of prostaglandin E2 who received celecoxib (HR = 1.57; 95% CI, 0.87 to 2.84; P = .13). CONCLUSION Celecoxib use during chemotherapy adversely affected survival in patients with breast cancer, and the effect was more marked in PTGS2-low and/or estrogen receptor–negative tumors. COX-2 inhibitors should preferably be avoided during docetaxel use in patients with breast cancer who are undergoing NAC.

scholarly journals Efficacy and safety of cisplatin and paclitaxel (PlaTax regimen) in the neoadjuvant treatment of patients with stage II–III triple-negative breast cancer

2020 ◽  
Vol 16 (2) ◽  
pp. 25-37
Author(s):  
O. O. Gordeeva ◽  
I. V. Kolyadina ◽  
L. G. Zhukova ◽  
I. P. Ganshina ◽  
G. V. Vyshinskaya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Progression Free Survival ◽  
Stage Ii ◽  
Efficacy And Safety ◽  
Treatment Results ◽  
Free Survival

Background. Treatment results for the patients with stage II–III triple negative breast cancer (TN BC) have to be improved. Not only the new treatment regimens, but new predictive and prognostic factors should to be developed.Materials and methods. We included 98 patients with stage II–III TN BC in our study. We studied efficacy and safety of PlaTax regimen (cisplatin 75 mg / m2 day 1 + paclitaxel 80 mg / m2 days 1, 8, 15, course every 4 weeks) in this cohort of patients. We assessed pathologic response, survival and factors, which were relevant for predicting response and prognose survival.Results. PlaTax regimen is characterized by high efficacy and tolerable toxicity. Clinical efficacy was 85.8 %, pCR achievement was 60.5 %, tpCR achievement was 58.1 %. The regimen has low haematological toxicity (neutropenia III–IV grades – 4.1 %); the most frequent adverse events were polyneuropathy (18.5 %) and decreased renal function (24.5 %). 3-year progression-free survival was 68.4 %, most of the relapses (92 %) occurred during first 2 years. 3 year overall survival was 77.6 %. The most relevant predictive factor was level of Ki-67 ≥50 % (pCR 38.5 % vs. 68.7 %, p = 0.038). pCR achievement was the most important prognostic factor, resulting in improved 3-year progressionfree survival (44.3 % vs. 89.1 %, p <0.0001), and 3-year overall survival (61.5 % vs. 91.6 %, p = 0.001). Not only the residual disease, but also the size of residual tumor was important from prognostic point of view. Other important prognostic factors were size of the tumor, status of regional lymph nodes, grade. Delay in surgical treatment more than a month lead to decreased 3-year progression-free survival: 87.1 % vs. 62.5 % (p = 0.047).Conclusions. Our data suggest that studied regimen could be an option for patients with stage II–III TN BC. The assessment of the predictive and prognostic factors will help improve the treatment results for patients with stage II–III TN BC.

scholarly journals Outcomes in Clinically Relevant Patient Subgroups From the EMBRACA Study: Talazoparib vs Physician’s Choice Standard-of-Care Chemotherapy

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Hope S Rugo ◽  
Johannes Ettl ◽  
Sara A Hurvitz ◽  
Anthony Gonçalves ◽  
Kyung-Hun Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Confidence Interval ◽  
Clinical Benefit ◽  
Odds Ratio ◽  
Objective Response ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
Duration Of Response ◽  
Patient Subgroups

Abstract Background Talazoparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that causes death in cells with breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations. Methods EMBRACA (NCT01945775) was a randomized phase III study comparing efficacy, safety, and patient-reported outcomes (PROs) of talazoparib (1 mg) with physician’s choice of chemotherapy (PCT: capecitabine, eribulin, gemcitabine, vinorelbine) in locally advanced or metastatic breast cancer with a germline BRCA1/2 (gBRCA1/2) mutation. Prespecified patient subgroups were analyzed for progression-free survival, objective response, clinical benefit, duration of response, and safety. PROs were evaluated in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) or triple-negative breast cancer (TNBC) subgroups. Results Of 431 patients, 287 were randomly assigned to talazoparib and 144 to PCT. Prespecified subgroup analyses showed prolonged progression-free survival with talazoparib (HR+/HER2−: hazard ratio = 0.47, 95% confidence interval = 0.32 to 0.71; TNBC: hazard ratio = 0.60, 95% confidence interval = 0.41 to 0.87) and greater objective response rate (odds ratio = 1.97 to 11.89), clinical benefit rate (odds ratio = 2.05 to 7.77), and duration of response with talazoparib in all subgroups. PROs in HR+/HER2− and TNBC subgroups showed consistent overall improvement and delay in time to definitive clinically meaningful deterioration with talazoparib vs PCT. Across subgroups, common adverse events included anemia, fatigue, and nausea with talazoparib and neutropenia, fatigue, and nausea with PCT. Seven patients (2.4%) receiving talazoparib had grade II alopecia and 22.7% had grade I alopecia. Conclusions Across all patient subgroups with gBRCA-mutated advanced breast cancer, talazoparib demonstrated clinically significant superiority in outcomes compared with PCT.

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