Disease-free survival as a predictor of overall survival in localized renal cell carcinoma following initial nephrectomy: A retrospective analysis of Surveillance, Epidemiology and End Results-Medicare datac.

OBJECTIVES: This study aimed to assess whether disease-free survival (DFS) may serve as a predictor for long-term survival among patients with intermediate-high risk or high risk renal cell carcinoma (RCC) post-nephrectomy when overall survival (OS) is unavailable. METHODS: The Surveillance, Epidemiology and End Results-Medicare database (2007-2016) was used to identify patients with non-metastatic intermediate-high risk and high risk RCC post-nephrectomy. Landmark analysis and Kendall's τ were used to evaluate the correlation between DFS and OS. Multivariable regression models were used to quantify the incremental OS post-nephrectomy associated with increased time to recurrence among patients with recurrence, adjusting for baseline covariates. RESULTS: A total of 643 patients were analyzed; mean age of 75 years; >95% of patients had intermediate-high risk RCC at diagnosis; 269 patients had recurrence post-nephrectomy. For patients with versus without recurrence at the landmark points of 1, 3, and 5 years post-nephrectomy, the 5-year OS were 37.0% versus 70.1%, 42.3% versus 72.8%, and 53.2% versus 78.6%, respectively. The Kendall's τ between DFS and OS post-nephrectomy was 0.70 (95% CI: 0.65, 0.74; p < 0.001). After adjusting for baseline covariates, patients with one additional year of time to recurrence were associated with 0.73 years longer OS post-nephrectomy (95% CI: 0.40, 1.05; p < 0.001). CONCLUSION: The significant positive association of DFS and OS among patients with intermediate-high risk and high risk RCC post-nephrectomy from this study supports the use of DFS as a potential predictor of OS for these patients when OS data are immature.

Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma.

BACKGROUND: Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence. METHODS: In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year). The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point. RESULTS: A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval [CI], 0.53 to 0.87; P = 0.002 [two-sided]). The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96). Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred. CONCLUSIONS: Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.).

Treatment patterns and survival in metastatic breast cancer patients by tumor characteristics.

OBJECTIVES: Study objectives were to compare the treatment patterns and clinical outcomes among metastatic breast cancer (mBC) patients by receipt of HER2-targeted agents and among subgroups of HER2-targeted agent users. RESEARCH DESIGN AND METHODS: Adult women newly diagnosed with mBC (index date) during 2008-2012 were selected from the Truven MarketScan databases and followed until end of enrollment or inpatient death. Patients with <12 months of data, pre-index primary cancers other than breast cancer, pregnancy, or HIV/AIDS were excluded. Study cohorts were users and nonusers of HER2-targeted agents and women with no treatment; and HER2-targeted agent subgroups by receipt of hormonal therapy (HT), de novo vs. recurrent status, and age group. Pre- and post-index breast cancer treatments were compared across cohorts. Relative risk of progression and death were evaluated among the subset of patients with mortality data. RESULTS: Of 18,059 eligible women selected, 14.6% were users of HER2-targeted agents, 71.1% were nonusers, and 14.3% untreated. HER2-targeted agent users received more aggressive cancer treatments compared to nonusers. HER2-targeted agent users were 33% more likely to progress and had a similar risk of death compared to nonusers. Among HER2-targeted agent subgroups, the risk of progression was 30% lower among HT+ patients vs. HT-, 32% lower for de novo vs. recurrent, and similar across age groups. The risk of death was 52% lower for HT+ vs. HT-, 35% lower for de novo vs. recurrent, and increased with age. LIMITATIONS: Identification of distant metastasis, tumor receptor expression and disease progression were based on claims data rather than on clinical assessment. CONCLUSIONS: Receipt of HER2-targeted agents (vs. non-HER2-targeted agents) was significantly associated with receipt of pre- and post-index breast cancer treatments. HER2-targeted agent users were more likely to progress but had a similar risk of death during follow-up. Among HER2-targeted agent subgroups, HT+ and de novo status were associated with a reduced risk of progression and death.

Healthcare Resource Use and Expenditures among Metastatic Breast Cancer Patients Treated with HER2-Targeted Agents.

Objective. To compare healthcare utilization (HCU) and costs of women newly diagnosed with metastatic breast cancer (mBC) by receipt of HER2-targeted agents (H2T) and among H2T subgroups. Methods. Adult women newly diagnosed with mBC (index date) during 2008-2012 were followed until enrollment end or inpatient death. Study cohorts were antineoplastic ± H2Ts, and no treatment; and subgroups of H2T patients stratified by receipt of hormonal therapy (HT+/HT-), by de novo versus recurrent disease status, and by age group. All-cause (ALL) and breast cancer related (BCR) HCU and costs (in 2012 dollars) were estimated using a generalized linear model. Results. Of 18,059 women, 14.6% were H2T users 71.1% nonusers, and 14.3% untreated. No treatment patients had the highest ALL and BCR inpatient HCU, and ALL emergency room HCU. H2Ts users had the highest ALL and BCR office visits, lab and diagnostic radiology, radiation treatments, other outpatient services, and prescription antineoplastics. Adjusted ALL and BCR costs were the highest for H2T users and, in H2T subgroups, higher for HT-versus HT+ and de novo versus recurrent, and declined with older age. Conclusions. Receipt of H2Ts was associated with greater levels of ALL and BCR HCU and costs. H2T subgroups of HT-, de novo, and younger age had higher HCU and costs, possibly indicating more aggressive treatments.