PERFORM: a non-interventional study assessing the patients' treatment starting with 1L palbociclib in HR+/HER2- ABC.

The prospective, non-interventional PERFORM study describes and analyzes the effectiveness of palbociclib in combination with endocrine therapy (aromatase inhibitor or fulvestrant) as first-line treatment for patients with locally advanced or metastatic HR+/HER2- breast cancer in the real-world setting in Germany and Austria. PERFORM will reflect current patient characteristics and routine treatment patterns including treatment sequences and time to subsequent (chemo)therapy. Besides, second-line treatment effectiveness and patient-relevant end points such as longitudinal patient-reported outcome measurements beyond disease progression will be analyzed. Accounting for the heterogenous real-world patient population, data on clinicopathologic subgroups underrepresented in clinical trials such as elderly or male will be analyzed. Taken together, PERFORM will close knowledge gaps from clinical trials in real world.

Palbociclib in combination with endocrine therapy is the standard first-line treatment for patients with advanced HR+/HER2- breast cancer. Data from clinical trials have shown high response rates and good tolerability. To support these data and close potential knowledge gaps, we conduct the multicenter, observational PERFORM study to evaluate the effectiveness and patient-reported outcomes in patients with advanced HR+/HER2- breast cancer treated with endocrine-based palbociclib therapy in routine clinical practice in Germany. Clinical Trial Registration: NCT04767594 (ClinicalTrials.gov) Sponsor: Pfizer Pharma GmbH, Linkstraße 10, D-10785 Berlin, Germany.

Mortality risk in a historical cohort of nuclear power plant workers in Germany: results from a second follow-up.

Possible health effects of low and protracted doses of ionizing radiation are relevant for persons who are exposed to an occupational context like nuclear industry workers. A historical cohort study was therefore conducted to examine mortality risks following occupational radiation exposure among 4,844 German nuclear power plant workers. This cohort included workers from ten nuclear power plants with an observational period from 1991 until 1997. The results of an enlarged cohort with 8,972 workers from all 17 nuclear power plants in West Germany are now available. During the extended follow-up period from 1991 to 2008, a total of 310 deaths among men were observed. The standardized mortality ratio (SMR) from all causes of deaths was estimated at 0.50 [95 % confidence interval (CI) 0.45-0.56]. A total of 126 deaths due to cancer occurred (SMR = 0.65; 95 % CI 0.51-0.82) and seven deaths due to leukemia (SMR = 1.23; 95 % CI 0.42-2.84). Overall, a reduced mortality compared to the general population of West Germany was observed indicating a healthy worker effect. In the dose-response analysis, no statistically significant risk due to ionizing radiation was seen. The hazard ratio (HR/mSv) for leukemia excluding chronic lymphocytic leukemia was estimated at 1.004 (95 % CI 0.997-1.011). In conclusion, the cohort is small and made up of young workers, most of whom were still employed at the end of the observational period in 2008. Results of the external analysis are difficult to interpret as influenced by a healthy worker effect. In the internal analysis, no excess of risk due to radiation was detected.

Assessment of prognosis by established prognosis scores and physicians' judgement in mRCC patients: an analysis of the STAR-TOR registry.

BACKGROUND: Temsirolimus is a mTOR inhibitor approved for the first-line treatment of advanced or metastatic renal cell carcinoma (a/mRCC) with poor prognosis. In treatment of a/mRCC several prognostic scoring systems are used. We assessed the prognostic value of these scores in a large temsirolimus treated cohort and compared the results with the physician's prognosis. METHODS: A German multicenter registry (STAR-TOR) for a/mRCC patients (NCT00700258) was established to evaluate the efficacy and safety of temsirolimus 25 mg weekly in a routine clinical setting. These prospective data were systematically analyzed and followed-up by an independent clinical research organization to compare established prognostic scores (MSKCC, IMDC and Hudes) with the risk assessment by treating physicians based on their medical expertise and match them with survival outcomes. RESULTS: This interim analysis included 547 patients between 02/2008 and 05/2015 in 87 centers. Either prognostic tool resulted in significant and clinically meaningful differentiation between good, intermediate and poor prognosis. However, physician's prognosis identified more patients with good prognosis (9.1% vs. 1.3%). In patients with good physician's prognosis and intermediate prognosis by MSKCC, overall survival was nearly doubled compared to consensual intermediate prognosis (26.6 vs. 13.6 months), albeit without reaching statistical significance (P=0.09). For poor prognosis assessed by the physician, MSKCC performed statistically better for differentiation between poor and intermediate prognosis with a median overall survival of 10.3 vs. 5.5 months (P<0.01). CONCLUSIONS: Physician's prognosis may be able to identify a subset of patients treated with temsirolimus with good prognosis when MSKCC-determines intermediate prognosis while the MSKCC score could identify patients which were falsely placed in the poor risk group by physicians.