scholarly journals Physicians’ Perception of the Evidence in Relation to Primary Endpoints of Clinical Trials on Breast Cancer

Breast Care ◽  
2021 ◽  
pp. 1-8
Author(s):  
Yi Zhang ◽  
Miao Liu ◽  
Houpu Yang ◽  
Shu Wang
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Local Treatment ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Absolute Difference ◽  
Chinese Society ◽  
Free Survival

<b><i>Objective:</i></b> To investigate physicians’ perception of the evidence of clinical trials on breast cancer. <b><i>Methods:</i></b> A survey was conducted by the Chinese Society of Breast Surgeons. We investigated the physicians’ perception of meaningful endpoints, appropriate follow-up duration, and clinically acceptable benefit through online questionnaires. <b><i>Results:</i></b> Among 278 validated questionnaires, the majority of the questions had no consistent answer. For local treatment, 30.6, 28.8, and 28.4% of participants regarded locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) as the most meaningful endpoint, respectively, 47.5% believed that 5-year follow-up can alter clinical practice, and 34.5% thought it should be &#x3e;10 years. In the adjuvant setting, 45.7, 38.5, and 12.9% regarded DFS, OS, and LRR as the most meaningful endpoint, respectively, 52.5% thought that 10-year follow-up was solid, while 37.4% thought that 5-year follow-up was enough. In the advanced setting, 49.6, 24.1, and 23.7% considered progression-free survival, quality of life, and OS the most meaningful endpoint, respectively, and 39.6 and 28.8% considered that a follow-up of 1 year and 3 years, respectively, was meaningful. Similarly, the clinically acceptable absolute difference was inconsistent. <b><i>Conclusion:</i></b> Most Chinese oncologists advocated that surrogate endpoints could be used in certain circumstances, though OS was the most reliable one in breast cancer studies. Doctors’ perceptions of follow-up time and magnitude of benefit vary widely, reflecting the fact that there are many unanswered questions about supporting the use of new cancer treatments; a common understanding needs to be reached, such as a very consensual surrogate endpoint and a meaningful sufficiently large therapeutic benefit.

Validation of MAF biomarker for response prediction to adjuvant bisphosphonates in 2 clinical trials: AZURE and NSABP-B34.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 513-513
Author(s):  
Alexander H. G. Paterson ◽  
Stewart J. Anderson ◽  
Roger Gomis ◽  
Joel [email protected] ◽  
Juan-Carlos Tercero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Disease Free Survival ◽  
Collaborative Group ◽  
Secondary Outcome ◽  
Control Group ◽  
Free Survival ◽  
Disease Free

513 Background: An Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis indicates that adjuvant bisphosphonates increase time to bone recurrence and survival in postmenopausal breast cancer patients, but results of individual trials have been inconclusive. Retrospective analyses of AZURE, a trial of adjuvant zoledronic acid, showed MAF (a transcription factor of the AP-1 family) amplification status predicted bisphosphonate benefit independently of menopause for invasive disease-free survival (IDFS) and overall survival (OS). Validation of MAF amplification status as a potential companion diagnostic for adjuvant bisphosphonates was confirmed using NSABP-B34 specimens. Methods: The randomized, placebo-controlled NSABP B-34 study of women with stage 1-3 breast cancer were assigned to adjuvant systemic therapy plus oral clodronate 1600 mg daily or placebo for 3 years. The primary endpoint was disease-free survival (DFS) with overall survival (OS) as a secondary outcome. MAF amplification was assessed by fluorescence in-situ hybridization on anonymized sections of breast tumor tissue in all patients with tumor samples and performed in a laboratory blind to treatment assignment. Protocol and analysis plans were pre-specified. Disease outcomes were analysed using intention to treat principles. Results: 2496 B-34 patients contributed tumor samples (from 2001-2004), of whom 1883 (75%) were evaluable (947 placebo and 936 clodronate). 1515 (80%) tumors were MAF negative (766 placebo and 749 clodronate) and 368 were MAF positive. At median follow-up of 108 months, MAF was prognostic for DFS, OS and bone-metastasis-free survival in the control group (MAF-positive vs MAF-negative: HRDFS=1·39, 95%CI 1·01-1·92; p=0.045; HROS=1·59, 95%CI 1·08-2·33; p=0.018; HRBM=2·03, 95%CI 1·13-3·68; p=0.016). In patients with MAF-negative tumors, clodronate gave higher DFS and OS than controls at 60 months (HRDFS=0·70, 95%CI 0·51-0·94; p=0.020 and HROS=0·59, 95%CI 0·37-0·93; p=0.024), the latter maintained through follow-up (HROS=0·74, 95%CI 0·54-1.00; p=0.047), but not in patients with MAF-positive tumors - consistent with previous AZURE results. Conclusions: MAF benefit prediction from adjuvant bisphosphonates was confirmed using specimens from 2 randomized clinical trials (AZURE and NSABP-B-34) conducted and analyzed in similar manner using the same validated tests and clinical endpoints. These results are evidence towards introducing MAF testing into clinical practice.

Overview of randomized perioperative polychemotherapy trials in women with early-stage breast cancer.

1997 ◽  
Vol 15 (7) ◽  
pp. 2526-2535 ◽  
Author(s):  
P C Clahsen ◽  
C J van de Velde ◽  
A Goldhirsch ◽  
J Rossbach ◽  
M R Sertoli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Free Survival ◽  
Node Negative ◽  
Disease Free

PURPOSE To determine whether perioperative polychemotherapy (PeCT) can significantly prolong the overall survival of women with early-stage breast cancer. METHODS A meta-analysis that used updated individual patient data from all available randomized trials of PeCT, both published and unpublished, was conducted. Data on 6,093 patients (1,124 deaths and 1,912 recurrences) from five clinical trials were available (median follow-up duration, 5.3 years; maximum, 11.3 years). RESULTS No significant effect of PeCT on overall survival was observed. However, patients who received PeCT had a significantly longer disease-free survival (hazards ratio [HR], 0.89; 95% confidence interval [CI], 0.82 to 0.98; P = .02). Time to local recurrence was significantly prolonged in the PeCT arm (HR, 0.68; 95% CI, 0.58 to 0.80; P < .0001). Likewise, there was a borderline significant difference in favor of PeCT in terms of time to distant metastases (HR, 0.90; 95% CI, 0.81 to 1.00; P = .05). Subgroup analyses suggest that node-negative women benefited the most from treatment. CONCLUSION At present, there is no evidence that PeCT is able to prolong overall survival in patients with early-stage breast cancer; however, further follow-up evaluation is required. PeCT significantly prolongs disease-free survival, especially in node-negative women, which emphasizes once more the need for clinical trials in this subgroup.

scholarly journals Indicadores (Outcomes) Primários e Secundários em Ensaios Clínicos Oncológicos: Definição e Usos

2014 ◽  
Vol 27 (4) ◽  
pp. 498
Author(s):  
António Vaz-Carneiro ◽  
Ricardo Da Luz ◽  
Margarida Borges ◽  
João Costa
Keyword(s):  
Clinical Trials ◽  
Methodological Issue ◽  
Objective Response ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patient Reported ◽  
Oncology Clinical Trials ◽  
Alternative Drug ◽  
Selection Of

<strong>Introduction:</strong> The proof of efficacy from a therapeutic intervention in oncology must be defined through well conducted clinical trials. One of the most important methodological issue is the outcome selection needed to calculate measures of association allowing definition of clinical efficacy.<br /><strong>Material and Methods:</strong> We designed a narrative revision based on some of the international regulatory instructions from drug agencies, as well as consensus papers from scientific oncology societies, listing and critically assessing each outcome used in oncology clinical trials.<br /><strong>Results:</strong> We identified as being the most important outcomes in oncology trials the overall survival, the progression free survival/ disease-free survival, the toxicity, the quality of life/patient- reported outcomes and the objective response rate.<br /><strong>Discussion:</strong> The selection of the primary outcome must be based on therapeutic efficacy as well as toxicity, expected survival, alternative drug regimens and even disease prevalence.<br /><strong>Conclusion:</strong> The selection of efficacy outcomes for clinical trials in oncology is very important and its selection must be well justified, and depends on the type of disease, the patients and the drug being studied.<br /><strong>Keywords:</strong> Clinical Trials as Topic; Neoplasms; Medical Oncology; Treatment Outcome.

scholarly journals Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor–Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial

2019 ◽  
Vol 37 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Thomas Ruhstaller ◽  
Anita Giobbie-Hurder ◽  
Marco Colleoni ◽  
Maj-Britt Jensen ◽  
Bent Ejlertsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Contralateral Breast Cancer ◽  
Disease Free Survival ◽  
Luminal Breast Cancer ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Disease Free

Purpose Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. Patients and Methods BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. Results Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. Conclusion Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

Re-Evaluating Disease-Free Survival as an Endpoint vs Overall Survival in Stage III Adjuvant Colon Cancer Trials

2021 ◽  
Author(s):  
Jun Yin ◽  
Mohamed E Salem ◽  
Jesse G Dixon ◽  
Zhaohui Jin ◽  
Romain Cohen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Surrogate Endpoint ◽  
Free Survival ◽  
A Value ◽  
Deficient Mismatch Repair ◽  
Disease Free

Abstract Background Disease-free survival with a 3-year median follow-up (3-year DFS) was validated as a surrogate for overall survival with a 5-year median follow-up (5-year OS) in adjuvant chemotherapy colon cancer (CC) trials. Recent data show further improvements in OS and survival after recurrence, in patients who received adjuvant FOLFOX. Hence, re-evaluation of the association between DFS and OS and determination of the optimal follow-up duration of OS to aid its utility in future adjuvant trials are needed. Methods Individual patient data from nine randomized studies conducted between 1998 and 2009 were included; three trials tested biologics. Trial-level surrogacy examining the correlation of treatment effect estimates of 3-year DFS with 5 to 6.5-year OS was evaluated using both linear regression (R2WLS) and Copula bivariate (R2Copula) models and reported with 95% confidence intervals (CIs). For R2, a value closer to 1 indicates a stronger correlation. Results Data from a total of 18,396 patients were analyzed (median age = 59 years; 54.0% male), with 54.1% having low-risk tumors (pT1-3 & pN1), 31.6% KRAS mutated, 12.3% BRAF mutated, and 12.4% microsatellite instability high/deficient mismatch repair tumors. Trial level correlation between 3-year DFS and 5-year OS remained strong (R2 =0.82, 95% CI = 0.67 to 0.98; R2 =0.92, 95% CI = 0.83 to 1.00) and increased as the median follow-up of OS extended. Analyses limited to trials that tested biologics showed consistent results. Conclusion Three-year DFS remains a validated surrogate endpoint for 5-year OS in adjuvant CC trials. The correlation was likely strengthened with 6 years of follow-up for OS.

Tamoxifen therapy in primary breast cancer: biology, efficacy, and side effects.

1989 ◽  
Vol 7 (6) ◽  
pp. 803-815 ◽  
Author(s):  
R R Love
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Primary Breast Cancer ◽  
Cancer Biology ◽  
Biological Effects ◽  
Disease Free Survival ◽  
Free Survival ◽  
Beneficial Effects ◽  
Tamoxifen Citrate ◽  
Disease Free

Since its introduction into clinical use in the early 1970s, the synthetic antiestrogen tamoxifen citrate has been shown to contribute to the control of human breast cancer in increasingly significant ways. While its mechanisms of action and pharmacology are incompletely understood, tamoxifen appears to act predominantly by blocking the action of estrogen by binding to the estrogen receptor. Clinical trials of tamoxifen for 1 to 2 years in primary breast cancer demonstrate consistent beneficial effects on disease-free survival, but only suggested beneficial effects on survival. Routine use of adjuvant tamoxifen for 5 years or more will depend on the results of ongoing large clinical trials of efficacy and detailed studies of unknown biological effects on other tissues.

scholarly journals Association of Cardiovascular Risk Factors With Cardiac Events and Survival Outcomes Among Patients With Breast Cancer Enrolled in SWOG Clinical Trials

2018 ◽  
Vol 36 (26) ◽  
pp. 2710-2717 ◽  
Author(s):  
Dawn L. Hershman ◽  
Cathee Till ◽  
Sherry Shen ◽  
Jason D. Wright ◽  
Scott D. Ramsey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Overall Survival ◽  
Clinical Trials ◽  
Survival Outcomes ◽  
Cardiac Events ◽  
Free Survival ◽  
Increased Risk

Background Cardiovascular disease is the primary cause of death among patients with breast cancer. However, the association of cardiovascular-disease risk factors (CVD-RFs) with long-term survival and cardiac events is not well studied. Methods We examined SWOG (formerly the Southwest Oncology Group) breast cancer trials from 1999 to 2011. We identified baseline diabetes, hypertension, hypercholesterolemia, and coronary artery disease by linking trial records to Medicare claims. The primary outcome was overall survival. Patients with both baseline and follow-up claims were examined for cardiac events. Cox regression was used to assess the association between CVD-RFs and outcomes. Results We identified 1,460 participants older than 66 years of age from five trials; 842 were eligible for survival outcomes analysis. At baseline, median age was 70 years, and median follow-up was 6 years. Hypertension (73%) and hypercholesterolemia (57%) were the most prevalent conditions; 87% of patients had one or more CVD-RF. There was no association between any of the individual CVD-RFs and overall survival except for hypercholesterolemia, which was associated with improved overall survival (hazard ratio [HR], 0.73; 95% CI, 0.57 to 0.93; P = .01). With each additional CVD-RF, there was an increased risk of death (HR, 1.23; 95% CI, 1.08 to 1.40; P = .002), worse progression-free survival (HR, 1.12; 95% CI, 1.00 to 1.25; P = .05), and marginally worse cancer-free survival (HR, 1.15; 95% CI, 0.99 to 1.34; P = .07). The relationship between baseline CVD-RFs and cardiac events was analyzed in 736 patients. A strong linear association between the number of CVD-RFs and cardiac event was observed (HR per CVD-RF, 1.41; 95% CI, 1.17 to 1.69; P < .001). Conclusion Among participants in clinical trials, each additional baseline CVD-RF was associated with an increased risk of cardiac events and death. Efforts to improve control of modifiable CVD-RFs are needed, especially among those with multiple risk factors.

scholarly journals Phyllodes tumor of the breast: a clinic-pathologic study of 77 cases in a Hispanic cohort

2015 ◽  
pp. 104-108 ◽  
Author(s):  
Carlos Andres Ossa Gomez ◽  
Fernando Herazo ◽  
Monica Gil ◽  
Carolina Echeverry ◽  
Gonzalo Angel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Phyllodes Tumor ◽  
Cancer Registries ◽  
Local Relapse ◽  
Free Survival ◽  
Phyllodes Tumors ◽  
Mean Size ◽  
Reported Data

Introduction: Breast Phyllodes tumors are rare breast tumors present in less than 1% of new cases of breast cancer, usually occurring among middle-aged women (40-50 yrs). Objective: This study shows diagnostic experience, surgical management and follows up of patients with this disease during a period of ten years in a oncology referral center. Methods: Retrospectively, breast cancer registries at the institution were reviewed, identifying 77 patients with Phyllodes tumors between 2002 and 2012, who had been operated on at the Instituto de Cancerología - Clínica Las Américas, in Medellín (Colombia). Clinical and histopathological data belonging to these cases was captured and analyzed and descriptive statistics were used. Results: The follow up median was 22.5 months (IQR: 10.5-60.0), average age was 47.2 yrs (SD: 12.4), mean tumor size was 3.6 cm (SD: 4.6), 88.3% of the patients (68 cases) presented negative margins and none of them received adjuvant chemotherapy. Of the patients with Phyllodes tumors; 33.8% had benign, 31.2% had borderline and 35.0% had malignant tumor. Disease-free survival was 85.8% and overall survival was 94.5%. Discussion: Reported data in this article is in accordance with what has been reported in worldwide literature. In our cohort even the high mean size of the tumors, the risk of local relapse and metastatic disease is low than previously reported in literature. Trials with longer follow up and molecular trials in Phyllodes tumors are necessary to understand the behavior of these tumors in Hispanics population.

5-Year Results of Dose-Intensive Sequential Adjuvant Chemotherapy for Women With High-Risk Node-Positive Breast Cancer: A Phase II Study

1999 ◽  
Vol 17 (4) ◽  
pp. 1118-1118 ◽  
Author(s):  
C. Hudis ◽  
M. Fornier ◽  
L. Riccio ◽  
D. Lebwohl ◽  
J. Crown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Pilot Study ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Free Survival ◽  
Dose Dense ◽  
Disease Free

PURPOSE: We conducted a phase II pilot study of dose-intensive adjuvant chemotherapy with doxorubicin followed sequentially by high-dose cyclophosphamide to determine the safety and feasibility of this dose-dense treatment and to estimate the disease-free and overall survival in breast cancer patients with four or more involved axillary lymph nodes. PATIENTS AND METHODS: Seventy-three patients received adjuvant treatment with four cycles of doxorubicin 75 mg/m2 as an intravenous bolus every 21 days, followed by three cycles of cyclophosphamide 3,000 mg/m2 every 14 days with granulocyte colony-stimulating factor support. RESULTS: Seventy-one patients were assessable, and all but two completed all planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. Median disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and overall survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSION: Our pilot study of doxorubicin followed by cyclophosphamide demonstrates the safety and feasibility of the sequential dose-dense plan. Long-term follow-up, although noncomparative, is promising. However, this regimen is associated with a higher incidence of toxicity (and also higher costs) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose-dense approach have been completed but not yet reported. Because the sequential plan can decrease overlapping toxicities, it is an appropriate platform for the addition of newer active agents, such as taxanes or monoclonal antibodies.

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