Julia J. Perkins

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.

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

Abstract 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

Association Between Breast Cancer Disease Progression and Workplace Productivity in the United States

11 090 for women with CT-1L and

Abstract P1-11-07: The relationship between breast cancer progression and workplace productivity in the US

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.

Abstract P3-07-23: Patient characteristics, clinical and economic outcomes of women with first-line therapy for HR+/HER2- metastatic breast cancer in a large US managed care health plan: Chemotherapy first vs. no chemotherapy first

Objective: Determine workplace productivity losses attributable to breast cancer progression. Methods: Longitudinal analysis linking 2005 to 2012 medical and pharmacy claims and workplace absence data in the US patients were commercially insured women aged 18 to 64 diagnosed with breast cancer. Productivity was measured as employment status and total quarterly workplace hours missed, and valued using average US wages. Results: Six thousand four hundred and nine women were included. Breast cancer progression was associated with a lower probability of employment (hazard ratio [HR] = 0.65, P < 0.01) and increased workplace hours missed. The annual value of missed work was

Abstract P3-07-24: Clinical characteristics and treatment utilization by tumor subtype among metastatic breast cancer patients in a large US managed care health plan

24,166 for non-metastatic and

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

30,666 for metastatic patients. Thus, progression to metastatic disease is associated with an additional

Clinical Characteristics, Treatment Patterns And Health Care Utilization In Er+/Her2- Metastatic Postmenopausal Breast Cancer Patients: Results From A Retrospective Medical Record Review In The United States

6500 in lost work time (P < 0.05), or 14% of average US wages. Conclusions: Breast cancer progression leads to diminished likelihood of employment, increased workplace hours missed, and increased cost burden.

Treatment and Patient Burden in ER+ HER2- Metastatic Breast Cancer: Results From a Physician Survey in the United States

Background: A significant proportion of women with breast cancer leave employment due to their disease. Little is known about the effects of breast cancer progression on productivity among those who remain employed. We sought to determine the effect of disease progression on workplace productivity among women with breast cancer. Methods: By linking health insurance claims data to workplace productivity data, a longitudinal dataset of women with breast cancer was constructed. The study cohort consisted of commercially insured women aged 18 to 64 in the US who were treated for any type of breast cancer between 2005 and 2012. Disease stage was measured through diagnosis codes and treatments observed, to classify women into the following breast cancer groups in each 90-day quarter: local; locally advanced; other non-metastatic; metastatic, 1st line therapy; metastatic, 2nd line therapy; metastatic, ≥ 3rd line therapy; metastatic, end-of-life care. Progression was defined as movement to a more advanced disease stage. Workplace productivity was measured as employment status and total hours away from work per quarter. Covariates included employer industry, comorbidities, age, region of residence, and a time trend. Reduced workplace productivity was valued using average U.S. wages by industry. Kaplan Meier analysis was used to test whether women whose cancer progressed were more likely to drop out of our employment-based sample. Linear and Heckman models were used to measure the effect of disease progression on workplace hours missed. The Heckman model was used to correct for selection bias, given that healthier women may be more likely to remain in our employment-based dataset. Results: The study cohort included 6,409 women. Mean patient age was 52.0 years (SD: 7.7). The mean number of Charlson comorbidities was 0.52 per patient (SD: 2.9). The majority of our employment-based sample had non-metastatic breast cancer (90.7%). Breast cancer progression was associated with a lower probability of employment (hazard ratio = 0.65, P Conclusions: Breast cancer progression leads to increased workplace hours missed, with greater hours missed among those with more advanced disease. Avoiding or delaying disease progression could bring productivity gains to the workplace in addition to the benefits to the patient. Support: This study was funded by Pfizer Inc. Citation Format: Yin W, Horblyuk R, Perkins JJ, Sison S, Smith G, Snider JT, Wu Y, Philipson TJ. The relationship between breast cancer progression and workplace productivity in the US. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-11-07.