scholarly journals Methods and Designs of Modern Breast Cancer Confirmatory Trials

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2757
Author(s):  
Julien Péron ◽  
Thibaut Reverdy ◽  
Colette Smenteck ◽  
Marion Cortet ◽  
Benoît You ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Data Extraction ◽  
Composite Endpoint ◽  
Breast Cancer Diagnosis ◽  
Evidence Base ◽  
New Drugs ◽  
Phase Iii ◽  
Data Extraction Form ◽  
Confirmatory Trials ◽  
Over Time

Background: The benefit–risk assessments of new drugs for breast cancer (BC) face several challenges, as all stakeholders do not agree on the evidence bar required for market authorization, and by the fragmentation of breast cancer diagnosis. The aim of this study was to describe the changes in methods and designs of breast cancer confirmatory trials. Methods: All phase III randomized trials published between 2001 and 2020 and assessing systemic BC therapies were included. Trials’ main characteristics, endpoints, and statistical methods were collected using a standardized data extraction form. Results: A total of 347 randomized controlled trials (RCTs) met the inclusion criteria. While most older trials (79%) included all subtypes of breast cancer, most recent trials populations were limited to one large intrinsic BC subgroup (69%). The use of gatekeeping testing strategies increased dramatically from 9% to 71%. The use of overall survival (OS) as an endpoint in the trials increased over time, but its use as a primary endpoint remained infrequent. The inclusion of OS testing in a hierarchical sequence in case of positive testing of a tumor-centered or composite endpoint appeared to have become the new standard. Conclusion: Our findings indicate some improvements in the quality of the evidence-base supporting new breast cancer drugs. The rigorous assessment of patient-relevant endpoints has increased over time, but this improvement is mainly related to the analysis of OS as a secondary endpoint analyzed in a hierarchical sequence.

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer

2020 ◽  
pp. 106002802096654
Author(s):  
John M. Seligson ◽  
Alexandra M. Patron ◽  
Michael J. Berger ◽  
R. Donald Harvey ◽  
Nathan D. Seligson
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
English Language ◽  
Triple Negative ◽  
Data Extraction ◽  
Phase Iii ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Topoisomerase 1 ◽  
Antibody Drug

Objective: To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease. Data Sources: A literature search was conducted utilizing PubMed and MEDLINE databases, applicable published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and September 3, 2020. Keywords included sacituzumab govitecan (-hziy), IMMU-132, Trop-2 (trophoblast cell-surface antigen 2), and TACSTD2. Study Selection and Data Extraction: All English-language trials involving sacituzumab govitecan for mTNBC were included and discussed. Data Synthesis: Sacituzumab govitecan is an antibody-drug conjugate targeted for Trop-2 and conjugated to the topoisomerase-1 inhibitor SN-38. It was granted accelerated Food and Drug Administration approval based on a phase I/II single-arm, multicenter study (n = 108), which reported an overall response rate of 33.3% and median duration of response of 7.7 months (95% CI = 4.9-10.8 months). Common adverse reactions include nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, abdominal pain, and respiratory infection. A confirmatory, randomized phase III clinical trial is ongoing (NCT02574455). Relevance to Patient Care and Clinical Practice: This review covers the efficacy, safety, and clinical use of sacituzumab govitecan, a third-line drug with activity in mTNBC. Conclusion: Sacituzumab govitecan is a novel targeted treatment with promising activity in mTNBC.

Phase III Trial of Concurrent or Sequential Adjuvant Chemoradiotherapy After Conservative Surgery for Early-Stage Breast Cancer: Final Results of the ARCOSEIN Trial

2007 ◽  
Vol 25 (4) ◽  
pp. 405-410 ◽  
Author(s):  
Alain Toledano ◽  
David Azria ◽  
Pascal Garaud ◽  
Alain Fourquet ◽  
Daniel Serin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locoregional Recurrence ◽  
Early Stage ◽  
Treatment Protocol ◽  
Disease Free Survival ◽  
New Drugs ◽  
Phase Iii ◽  
Adjuvant Chemoradiotherapy ◽  
Free Survival ◽  
Significant Difference

Purpose In 1996, we initiated the French multicenter phase III randomized trial to compare the effect on disease-free survival (DFS) of concurrent versus sequential chemotherapy (CT) and radiotherapy (RT) after breast-conserving surgery for stages I and II breast cancer. This report presents the clinical results with a median follow-up of 60 months. Patients and Methods Between February 1996 and April 2000, 716 patients were entered onto this trial. Adjuvant treatment began within 6 weeks after surgery. Sequential treatment of CT administered first followed by RT was compared with concurrent treatment of CT administered with RT. The CT regimen consisted of mitoxantrone (12 mg/m2), fluorouracil (500 mg/m2), and cyclophosphamide (500 mg/m2) on day 1, and it was repeated every 21 days for six courses. RT was delivered to the breast and, when indicated, to the regional lymphatics. Results There was no statistically significant difference in treatment in the 5-year DFS (80% in both groups; P = .83), locoregional recurrence-free survival (LRFS; 92% in sequential v 95% in concurrent; P = .76), metastasis-free survival (87% in sequential v 84% in concurrent; P = .55), or overall survival (90% in sequential v 91% in concurrent; P = .76). Nevertheless, in the node-positive subgroup, the 5-year LRFS was statistically better in the concurrent arm (97% in concurrent v 91% in sequential; P = .02), corresponding to a risk of locoregional recurrence decreased by 39% (hazard ratio, 0.61; 95% CI, 0.38 to 0.93). Conclusion This treatment protocol remains an appealing clinical option for many women with operable breast cancer at a high risk of recurrence. Combination treatments with new drugs for breast cancer are warranted.

Trajectories of Objectively Measured Physical Function Among Older Breast Cancer Survivors in Comparison With Cancer-Free Controls

2021 ◽  
Author(s):  
Juhua Luo ◽  
Stephen J. Carter ◽  
Elizabeth M Cespedes Feliciano ◽  
Michael Hendryx
Keyword(s):  
Breast Cancer ◽  
Cancer Survivors ◽  
Physical Function ◽  
Grip Strength ◽  
Cancer Diagnosis ◽  
Gait Speed ◽  
Breast Cancer Survivors ◽  
Breast Cancer Diagnosis ◽  
Quadriceps Strength ◽  
Over Time

Abstract PURPOSE: Aging associated with progressive declines in physical function is well-known; however, little is known about the trajectories of physical function before and after breast cancer diagnosis. The current study examined the trajectories in objective measures of physical function over 20 years for women with breast cancer and matched controls. METHODS: 2712 community-dwelling women (452 breast cancer cases and 1:5 matched cancer-free controls) aged 65 years or older at baseline (1986-1988) within the Study of Osteoporotic Fractures were followed for 20 years. Objective physical function was assessed up to 9 times, including hand-grip strength, timed chair stand, gait speed and quadriceps strength. Linear mixed models were used to model physical function changes in terms of secular time trend, group (cases or controls), period (pre-and post-diagnosis status), and their interaction terms. RESULTS: We observed all measures of physical function declined over time. While no differences in trends between cases and controls during the pre-diagnosis period were observed, after cancer diagnosis, grip strength and gait speed declined significantly faster in cases than controls. Quadriceps strength significantly decreased ~7 pounds shortly after breast cancer diagnosis, and then improved over time. CONCLUSION: Our prospective study revealed that older breast cancer survivors had significantly worse declines in grip strength and gait speed and a sharp, short-term drop followed by gradual improvement over time in quadriceps strength, compared to women without cancer. These findings suggest exercise training targeting muscle strength and mobility would be beneficial among older breast cancer survivors.

scholarly journals Design of Tumor Biomarker–Monitoring Trials: A Proposal by the European Group on Tumor Markers

2013 ◽  
Vol 59 (1) ◽  
pp. 52-59 ◽  
Author(s):  
György Sölétormos ◽  
Michael J Duffy ◽  
Daniel F Hayes ◽  
Catharine M Sturgeon ◽  
Vivian Barak ◽  
...  
Keyword(s):  
Tumor Markers ◽  
Disease Status ◽  
Evidence Base ◽  
Tumor Burden ◽  
New Drugs ◽  
Phase Iii ◽  
Tumor Biomarker ◽  
Long Term Effects ◽  
Major Application ◽  
European Group

Abstract A major application of tumor biomarkers is in serial monitoring of cancer patients, but there are no published guidelines on how to evaluate biomarkers for this purpose. The European Group on Tumor Markers has convened a multidisciplinary panel of scientists to develop guidance on the design of such monitoring trials. The panel proposes a 4-phase model for biomarker-monitoring trials analogous to that in use for the investigation of new drugs. In phase I, biomarker kinetics and correlation with tumor burden are assessed. Phase II evaluates the ability of the biomarker to identify, exclude, and/or predict a change in disease status. In phase III, the effectiveness of tumor biomarker–guided intervention is assessed by measuring patient outcome in randomized trials. Phase IV consists of an audit of the long-term effects after biomarker monitoring has been included into standard patient care. Systematic well-designed evaluations of biomarkers for monitoring may provide a stronger evidence base that might enable their earlier use in evaluating responses to cancer therapy.

Breast Cancer Diagnosis in Women ≤ 40 versus 50 to 60 Years: Increasing Size and Stage Disparity Compared With Older Women Over Time

2006 ◽  
Vol 13 (8) ◽  
pp. 1072-1077 ◽  
Author(s):  
Katherina Zabicki ◽  
James A. Colbert ◽  
Francisco J. Dominguez ◽  
Michele A. Gadd ◽  
Kevin S. Hughes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Women ◽  
Cancer Diagnosis ◽  
Breast Cancer Diagnosis ◽  
Over Time

Endocrine Effects of Adjuvant Letrozole Compared With Tamoxifen in Hormone-Responsive Postmenopausal Patients With Early Breast Cancer: The HOBOE Trial

2009 ◽  
Vol 27 (19) ◽  
pp. 3192-3197 ◽  
Author(s):  
Emanuela Rossi ◽  
Alessandro Morabito ◽  
Francesca Di Rella ◽  
Giuseppe Esposito ◽  
Adriano Gravina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Early Breast Cancer ◽  
Phase Iii ◽  
Endocrine Effects ◽  
Phase Iii Trial ◽  
Treatment Groups ◽  
To Receive ◽  
Ongoing Phase ◽  
Over Time

Purpose We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. Patients and Methods Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. Conclusion Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

scholarly journals The Association of a Breast Cancer Diagnosis With Serum 25-Hydroxyvitamin D Concentration Over Time

2019 ◽  
Vol 188 (4) ◽  
pp. 637-645 ◽  
Author(s):  
Katie M O’Brien ◽  
Dale P Sandler ◽  
Melissa House ◽  
Jack A Taylor ◽  
Clarice R Weinberg
Keyword(s):  
Breast Cancer ◽  
Cancer Diagnosis ◽  
Breast Cancer Diagnosis ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Over Time

Randomized Phase III Study of Docetaxel Compared With Paclitaxel in Metastatic Breast Cancer

2005 ◽  
Vol 23 (24) ◽  
pp. 5542-5551 ◽  
Author(s):  
S.E. Jones ◽  
J. Erban ◽  
B. Overmoyer ◽  
G.T. Budd ◽  
L. Hutchins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Open Label ◽  
Global Quality ◽  
Global Quality Of Life ◽  
Phase Iii Study ◽  
Over Time

PurposeThis randomized, controlled, multicenter, open-label, phase III study compared docetaxel versus paclitaxel in patients with advanced breast cancer that had progressed after an anthracycline-containing chemotherapy regimen.Patients and MethodsPatients (n = 449) were randomly assigned to receive either docetaxel 100 mg/m2(n = 225) or paclitaxel 175 mg/m2(n = 224) on day 1, every 21 days until tumor progression, unacceptable toxicity, or withdrawal of consent.ResultsIn the intent-to-treat population, both the median overall survival (OS, 15.4 v 12.7 months; hazard ratio [HR], 1.41; 95% CI, 1.15 to 1.73; P = .03) and the median time to progression (TTP, 5.7 months v 3.6 months; HR, 1.64; 95% CI, 1.33 to 2.02; P < .0001) for docetaxel were significantly longer than for paclitaxel, and the overall response rate (ORR, 32% v 25%; P = .10) was higher for docetaxel. These results were confirmed by multivariate analyses. The incidence of treatment-related hematologic and nonhematologic toxicities was greater for docetaxel than for paclitaxel; however, quality-of-life scores were not statistically different between treatment groups over time.ConclusionDocetaxel was superior to paclitaxel in terms of OS and TTP. ORR was higher for docetaxel. Hematologic and nonhematologic toxicities occurred more frequently in the docetaxel group. The global quality-of-life scores were similar for both agents over time.

Change in patient-reported outomes over time from breast cancer diagnosis.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 210-210
Author(s):  
C. E. Hill-Kayser ◽  
C. Vachani ◽  
M. K. Hampshire ◽  
G. A. Di Lullo ◽  
J. M. Metz
Keyword(s):  
Breast Cancer ◽  
Cancer Survivors ◽  
Cancer Diagnosis ◽  
Late Effects ◽  
Breast Cancer Survivors ◽  
Breast Cancer Diagnosis ◽  
Survivorship Care ◽  
Convenience Sample ◽  
Patient Reported ◽  
Over Time

210 Background: Breast cancer survivors may be at risk for significant late effects after treatment. Understanding the patterns of change over time of patient reported outcomes (PRO) is often very challenging. Methods: Patient-reported data was gathered via a convenience sample frame from breast cancer survivors utilizing a publically available, free, Internet-based tool for creation of survivorship care plans. Available at www.livestrongcareplan.com and through the OncoLink website, the tool allows survivors to enter data regarding diagnosis, demographics, treatments received, and late effects experienced, and provides them with customized guidelines for future care. All data has been maintained anonymously with IRB approval. Results: 1,145 breast cancer survivors were queried with regard to PRO. Median age at diagnosis (dx) was 49 yrs, and median current age 52 yrs. Of users, 98% reported having had surgery; of these 56% underwent mastectomy and 49% lumpectomy (5% both). Similarly, 59% underwent sentinel LN biopsy, and 47% axilary dissection. Of the same cohort, 88% received chemotherapy and/or hormonal treatment, and 70% radiation therapy. The median time from dx until use of the care plan tool was 2 years (range 0-33 years). Late effects reported by survivors ≤ 2 and > 2 years from diagnosis are shown (see table). Overall, survivors ≤ 2 years from dx were more likely to note changes in skin color or texture; those > 2 years from diagnosis were more likely to note osteopenia, lymphedema, and sexual changes. Patient reported cognitive changes, arm pain/numbness/tingling, and loss of shoulder flexibility did not differ between the two groups. Conclusions: This anonymous tool uses a convenience sample frame to gather PRO after breast cancer diagnosis/ treatment. PRO varied significantly with time since dx, with more late effects reported > 2 years from dx. This information may be of use during patient counseling and survivorship care delivery. [Table: see text]

scholarly journals Endocrine Therapy Initiation From 2001 to 2008 Varies by Age at Breast Cancer Diagnosis and Tumor Size

2012 ◽  
Vol 8 (2) ◽  
pp. 113-120 ◽  
Author(s):  
Erin J. Aiello Bowles ◽  
Diana S.M. Buist ◽  
Jessica Chubak ◽  
Onchee Yu ◽  
Jeanene Johnson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Cancer Diagnosis ◽  
Patient Preferences ◽  
Tumor Size ◽  
Breast Cancer Diagnosis ◽  
Therapy Initiation ◽  
Over Time

Differential initiation over time, as well as by age and tumor size, suggests patient preferences and provider recommendations for endocrine therapy vary, despite guideline recommendations.

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