Faculty Opinions recommendation of Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer.

2008 ◽  
Author(s):  
Debu Tripathy
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Control ◽  
Tumor Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Time To Progression ◽  
End Points ◽  
Free Survival

scholarly journals Evaluation of Tumor Response, Disease Control, Progression-Free Survival, and Time to Progression As Potential Surrogate End Points in Metastatic Breast Cancer

2008 ◽  
Vol 26 (12) ◽  
pp. 1987-1992 ◽  
Author(s):  
Tomasz Burzykowski ◽  
Marc Buyse ◽  
Martine J. Piccart-Gebhart ◽  
George Sledge ◽  
James Carmichael ◽  
...  
Keyword(s):  
Disease Control ◽  
Tumor Response ◽  
Rank Correlation ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Time To Progression ◽  
First Line ◽  
End Points ◽  
Free Survival ◽  
Hazard Ratios

Purpose Overall survival (OS) can be observed only after prolonged follow-up, and any potential effect of first-line therapies on OS may be confounded by the effects of subsequent therapy. We investigated whether tumor response, disease control, progression-free survival (PFS), or time to progression (TTP) could be considered a valid surrogate for OS to assess the benefits of first-line therapies for patients with metastatic breast cancer. Patients and Methods Individual patient data were collected on 3,953 patients in 11 randomized trials that compared an anthracycline (alone or in combination) with a taxane (alone or in combination with an anthracycline). Surrogacy was assessed through the correlation between the end points as well as through the correlation between the treatment effects on the end points. Results Tumor response (survival odds ratio [OR], 6.2; 95% CI, 5.3 to 7.0) and disease control (survival OR, 5.5; 95% CI, 4.8 to 6.3) were strongly associated with OS. PFS (rank correlation coefficient, 0.688; 95% CI, 0.686 to 0.690) and TTP (rank correlation coefficient, 0.682; 95% CI, 0.680 to 0.684) were moderately associated with OS. Response log ORs were strongly correlated with PFS log hazard ratios (linear coefficient [ρ], 0.96; 95% CI, 0.73 to 1.19). Response and disease control log ORs and PFS and TTP log hazard ratios were poorly correlated with log hazard ratios for OS, but the confidence limits of ρ were too wide to be informative. Conclusion No end point could be demonstrated as a good surrogate for OS in these trials. Tumor response may be an acceptable surrogate for PFS.

Phase III Double-Blind Trial of Arzoxifene Compared With Tamoxifen for Locally Advanced or Metastatic Breast Cancer

2007 ◽  
Vol 25 (31) ◽  
pp. 4967-4973 ◽  
Author(s):  
VijayaLaxmi Deshmane ◽  
S. Krishnamurthy ◽  
Allen S. Melemed ◽  
Patrick Peterson ◽  
Aman U. Buzdar
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Response ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Response Duration ◽  
Median Response ◽  
Free Survival ◽  
Time To Treatment Failure

Purpose To compare the efficacy of arzoxifene with tamoxifen for the treatment of locally advanced or metastatic breast cancer. Patients and Methods Women with estrogen- or progesterone-receptor–positive breast cancer who had not received prior systemic therapy, or who had relapsed more than 12 months after stopping adjuvant hormonal therapy, were randomly assigned to receive 20 mg arzoxifene or 20 mg tamoxifen daily. Each treatment arm was to have 240 patients enrolled. The primary end point was progression-free survival. Secondary end points included other measures of tumor response, overall survival, and safety. Results Enrollment was stopped when a planned interim analysis of the first 200 patients suggested arzoxifene to be significantly inferior to tamoxifen. The median progression-free survival for the 352 patients who had been randomly assigned when enrollment was stopped was 4.0 months (95% CI, 3.4 to 5.6 months) for the arzoxifene group and 7.5 months (95% CI, 5.9 to 8.8 months) for the tamoxifen group. On-study progression-free survival (P = .011) and time to treatment failure (P = .029) also favored tamoxifen. Overall tumor response rate and median response duration were comparable between the groups. Adverse events were similar between the treatments, except for nausea (more frequent with arzoxifene) and vaginal discharge (more frequent with tamoxifen). Conclusion Tamoxifen produced significantly longer progression-free survival and time to treatment failure compared with arzoxifene in the treatment of locally advanced and metastatic breast cancer. There were no significant differences between tumor response rate, clinical benefit rate, or median response duration.

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.

Phase III Study of Intravenous Vinorelbine in Combination With Epirubicin Versus Epirubicin Alone in Patients With Advanced Breast Cancer: A Scandinavian Breast Group Trial (SBG9403)

2004 ◽  
Vol 22 (12) ◽  
pp. 2313-2320 ◽  
Author(s):  
Bent Ejlertsen ◽  
Henning T. Mouridsen ◽  
Sven T. Langkjer ◽  
Jorn Andersen ◽  
Johanna Sjöström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Complete Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Severe Toxicity ◽  
Free Survival

Purpose To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer. Patients and Methods A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, or epirubicin 90 mg/m2 IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1,000 mg/m2 (950 mg/m2 from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses. Results Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P = .15). The complete response rate was significantly superior in the combination arm (17% v 10%; P = .048) as was median duration of progression-free survival (10.1 months v 8.2 months; P = .019). Median survival was similar in the two arms (19.1 months v 18.0 months; P = .50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms. Conclusion Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival.

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