Treatment patterns and real world clinical outcomes in ER+/HER2- post-menopausal metastatic breast cancer patients in the United States.

BACKGROUND: With several new therapies becoming available, treatment of metastatic breast cancer (mBC) is evolving. The objective of this study is to describe patient characteristics, treatment patterns and real-world clinical outcomes in post-menopausal women with ER+, HER2- mBC and to obtain insight into patient outcomes and potential unmet needs with current therapies. METHODS: The current study is a physician survey followed by a retrospective chart review of patient medical records by physicians in the US between March and April 2015. One hundred three physicians were asked to complete an online survey aiming to understand their satisfaction and expectations with current available treatments and potential areas of unmet need for mBC patients. Medical records from 178 females were extracted for the chart review. Using these data from medical records, patient characteristics and treatment patterns were analyzed descriptively. Time to progression (TTP) on first line, and progression-free survival (PFS) on second and third line of therapy were analyzed using the Kaplan-Meier method. RESULTS: Sixty-seven percent (n = 119) of patients had metastatic disease at initial diagnosis of breast cancer. Mean age at chart data extraction was 65.8 (SD: 9.4) years. Aromatase inhibitors (AIs) were prescribed for 58% and around 13% of patients in first line and second line, respectively. Chemotherapy was prescribed to 14% in first line and 31% in second line. Median TTP on first line therapy was 12 months for patients receiving AIs as compared to 7.9 months for patients receiving chemotherapy. Across all treatment lines, bone pain and fatigue were reported as the main symptoms associated with disease progression which had an impact on patient quality of life. Physicians expressed that prolonging life was deemed the most important treatment goal, followed by preservation or improvement of quality of life. CONCLUSION: In this study the majority of patients received endocrine therapy as first line treatment and current therapies still resulted in a short time to progression in first line. Results from the chart review and the physician survey highlight a quantitative unmet need for more effective treatments which delay disease progression and improve survival outcomes while maintaining quality of life.

Clinical and economic outcomes by first-line treatment among women with HR+/HER2- metastatic breast cancer in a large US health plan database.

BACKGROUND: Guidelines recommend that women with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) initiate hormonal therapy before chemotherapy. This study compared outcomes of women with mBC who received chemotherapy first vs hormonal therapy. METHODS: A retrospective cohort study of women with mBC was conducted using a large US commercial health plan database between January 1, 2008-April 30, 2013. Subjects had evidence of a HR+/HER2- tumor sub-type in a cancer registry and use of chemotherapy or hormonal therapy in claims. Subjects were continuously enrolled for ≥6 months after metastasis and assigned to cohorts for receiving chemotherapy only or hormonal therapy only during first-line (CT-1L vs HT-1L). Adjusted incidence rates of clinically significant events were compared using a negative binomial model, and adjusted healthcare costs were compared using a generalized linear model. RESULTS: Three hundred and twenty-four women with HR+/HER2- mBC met the selection criteria; 179 (55%) received CT-1L and 145 (45%) received HT-1L. Mortality rates did not differ between cohorts (unadjusted incidence rate ratio (IRR) = 1.67, 95% CI = 0.82-3.46; adjusted IRR = 0.64, 95% CI = 0.32-1.27). Adjusted average total all-cause healthcare costs were $11 090 for women with CT-1L and $6743 for women with HT-1L (cost ratio =1.64, 95% CI =1.36-1.99). CONCLUSIONS: Observed use of first-line chemotherapy (>50%) was higher than expected given the HR + molecular profile of the tumors. Chemotherapy use during first-line did not appear to be associated with a survival benefit, but was associated with significantly higher costs compared with the use of hormonal therapy during first-line; however, this comparison is limited by demographic and baseline characteristic differences between the two cohorts. This study contributes to understanding real-world treatment patterns and the associated clinical and economic outcomes of using chemotherapy vs hormonal therapy as a first-line treatment option for the HR+/HER2- mBC population.

Depth of remission is a prognostic factor for survival in patients with metastatic renal cell carcinoma.

BACKGROUND: Response remains an important endpoint in clinical cancer trials. However, the prognostic utility of best tumor response in metastatic renal cell carcinoma (mRCC) remains vague. OBJECTIVE: To define the prognostic relevance of the depth of remission in mRCC. DESIGN, SETTING, AND PARTICIPANTS: Pooled data from the Pfizer database for 2749 patients from phase 2 and 3 clinical trials in mRCC were analyzed. Tumor shrinkage was categorized according to the best percentage change in the sum of the largest diameter of target lesions. Outcome was computed using Kaplan-Meier curves and correlation was assessed via Cox regression, including a 6-mo landmark. INTERVENTION: Sunitinib, sorafenib, axitinib, temsirolimus, or temsirolimus and interferon-α. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Categorized tumor shrinkage, overall survival (OS), progression free survival (PFS). RESULTS AND LIMITATIONS: Major tumor shrinkage of 60% or more occurred in approximately 10% of patients and was associated with median OS of 54.5 mo. OS expectations steadily decreased with depth of remission (26.4, 16.6, 10.4, and 7.3 mo). The association was maintained when stratified by type of therapy, line of therapy, and performance status. Cox proportional regression analyses for the 6-mo landmark confirmed the prognostic relevance of major tumor shrinkage (hazard ratio 0.29, 95% confidence interval 0.22-0.39; p<0.001). The major limitation of our study is the variability of imaging intervals among studies. CONCLUSIONS: This is the first and largest analysis of best tumor response in mRCC. We demonstrate that depth of remission is an independent prognostic factor in mRCC. PATIENT SUMMARY: It remains unknown whether tumor shrinkage during therapy is needed to achieve clinical activity in metastatic renal cell carcinoma. Our analysis shows that the magnitude of tumor shrinkage correlates with better survival in patients. This observation may be used as a clinical research tool in future trials. TRIAL REGISTRATION: NCT00054886, NCT00077974, NCT00267748, NCT00338884, NCT00137423, NCT00083889, NCT00065468, NCT00678392.

Prognostic significance of bone metastases and bisphosphonate therapy in patients with renal cell carcinoma.

BACKGROUND: Bone metastases (BMs) are frequently present in patients with metastatic renal cell carcinoma (mRCC) and cause significant morbidity. OBJECTIVE: The purpose of this analysis was to assess the impact of BMs and bisphosphonate therapy (BT) on outcomes in mRCC. DESIGN, SETTING, AND PARTICIPANTS: We conducted a pooled analysis of patients with mRCC treated from 2003 to 2011 in phase 2 and 3 trials. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statistical analyses were performed using Cox regression and the Kaplan-Meier method. RESULTS AND LIMITATIONS: We identified 2749 patients treated with sunitinib (n=1059), sorafenib (n=355), axitinib (n=359), temsirolimus (n=208), temsirolimus plus interferon-α (IFN-α) (n=208), or IFN-α (n=560), with 28% (n=781) having BMs. A total of 285 patients (10.4%) received BT. The presence of BMs in patients was associated with shorter overall survival (OS) when compared with patients without BMs (13.2 vs 20.2 mo, respectively; p<0.0001) and shorter progression-free survival (PFS) (5.1 vs 6.7 mo, respectively; p<0.0008). When stratified by risk groups, the presence of BMs was associated with shorter OS in all risk groups. The use of BT in patients with BMs was not associated with improved OS compared with patients who did not receive BT (13.3 vs 13.1 mo, respectively; p=0.3801) or improved PFS (5.1 vs 4.9 mo, respectively; p=0.1785). Bisphosphonate users with BMs did not have a decreased rate of skeletal-related events (SREs) compared with nonusers (8.6% vs 5.8%, respectively; p=0.191). In addition, BT was associated with increased rates of hypocalcemia, renal insufficiency, and osteonecrosis of the jaw (p<0.0001). Data were analyzed retrospectively. CONCLUSIONS: We confirm that the presence of BMs is associated with shorter survival in mRCC. BT did not affect survival or SRE prevention and was associated with increased toxicity. PATIENT SUMMARY: In this analysis, we demonstrate that bone metastases are associated with shorter survival in patients with metastatic renal cell carcinoma. In addition, we call into question the utility of bisphosphonate therapy in this population.