Jenny J. Ko

The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study

BACKGROUND Previous prognostic models for second-line systemic therapy in patients with metastatic renal cell carcinoma have not been studied in the setting of targeted therapy. We sought to validate the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in patients with metastatic renal cell carcinoma receiving next-line targeted therapy after progression on first-line targeted therapy. METHODS In this population-based study, we analysed patients who received second-line targeted therapy for metastatic renal cell carcinoma at 19 centres in Canada, USA, Greece, Japan, Singapore, South Korea, and Denmark. The primary endpoint was overall survival since the initiation of second-line therapy. We compared the prognostic performance of the IMDC model with the three-factor MSKCC model used for previously treated patients for overall survival since the start of second-line targeted therapy. FINDINGS Between Jan 1, 2005, and Nov 30, 2012, we included 1021 patients treated with second-line targeted therapy. Median overall survival since the start of second-line targeted therapy was 12·5 months (95% CI 11·3-14·3). Five of six predefined factors in the IMDC model (anaemia, thrombocytosis, neutrophilia, Karnofsky performance status [KPS] <80, and <1 year from diagnosis to first-line targeted therapy) were independent predictors of poor overall survival on multivariable analysis. The concordance index using all six prognostic factors (ie, also including hypercalcaemia) was 0·70 (95% CI 0·67-0·72) with the IMDC model and was 0·66 (95% CI 0·64-0·68) with the three-factor MSKCC model. When patients were divided into three risk categories using IMDC criteria, median overall survival was 35·3 months (95% CI 28·3-47·8) in the favourable risk group (n=76), 16·6 months (14·9-17·9) in the intermediate risk group (n=529), and 5·4 months (4·7-6·8) in the poor risk group (n=261). INTERPRETATION The IMDC prognostic model can be applied to patients previously treated with targeted therapy, in addition to previously validated populations in first-line targeted therapy. The IMDC prognostic model in the second-line targeted therapy setting has an improved prognostic performance and is applicable to a more contemporary patient cohort than that of the three-factor MSKCC model. FUNDING DF/HCC Kidney Cancer SPORE P50 CA101942-01, Kidney Cancer Research Network of Canada, Canadian Institute for Health Research, Trust Family, Loker Pinard, Michael Brigham, and Gerald DeWulf.

First-, second-, third-line therapy for mRCC: benchmarks for trial design from the IMDC.

Background:Limited data exist on outcomes for metastatic renal cell carcinoma (mRCC) patients treated with multiple lines of therapy. Benchmarks for survival are required for patient counselling and clinical trial design.Methods:Outcomes of mRCC patients from the International mRCC Database Consortium database treated with 1, 2, or 3+ lines of targeted therapy (TT) were compared by proportional hazards regression. Overall survival (OS) and progression-free survival (PFS) were calculated using different population inclusion criteria.Results:In total, 2705 patients were treated with TT of which 57% received only first-line TT, 27% received two lines of TT, and 16% received 3+ lines of TT. Overall survival of patients who received 1, 2, or 3+ lines of TT were 14.9, 21.0, and 39.2 months, respectively, from first-line TT (P<0.0001). On multivariable analysis, 2 lines and 3+ lines of therapy were each associated with better OS (HR=0.738 and 0.626, P<0.0001). Survival outcomes for the subgroups were as follows: for all patients, OS 20.9 months and PFS 7.2 months; for those similar to eligible patients in the first-line ADAPT trial, OS 14.7 months and PFS 5.6 months; for those similar to patients in first-line TIVO-1 trial, OS 24.8 months and PFS 8.2 months; for those similar to patients in second-line INTORSECT trial, OS 13.0 months and PFS 3.9 months; and for those similar to patients in the third-line GOLD trial, OS 18.0 months and PFS 4.4 months.Conclusions:Patients who are able to receive more lines of TT live longer. Survival benchmarks provide context and perspective when interpreting and designing clinical trials.

Assessing the need for a nurse-led breast cancer telephone follow-up clinic in Alberta, Canada.

111 Background: Routine follow-up of breast cancer (BC) patients is largely transferred to primary care due to limited tertiary care resources and evidence supporting the acceptability and safety of this approach. It is unknown how BC survivors are faring in the community with treatment and surveillance goals, and if there is an unmet need for access to specialist care. Objectives of this cross-sectional study of BC survivors were to examine: concordance with endocrine therapy and follow-up recommendations; perceived need for help with achieving these recommendations; and, perceived need for a telephone follow-up clinic. METHODS Eligible participants were women with stage I-III BC diagnosed June 2006-September 2009 who had been seen in consultation at a tertiary cancer centre (TCC) in Alberta, Canada. 960 potentially eligible women were invited to participate via mail-out from the Alberta Cancer Registry. Consenting participants completed a structured telephone interview. Further patient, disease, endocrine therapy and surveillance data were obtained from the electronic chart and pharmacy databases. RESULTS 240 participants completed the telephone interview. 68.8% had been discharged from a TCC. 87.1% reported having had a clinical breast examination, and 97.1% with remaining breast tissue reported having had a surveillance mammogram within the past year. Concordance with endocrine therapy varied between pharmacy dispensing records (95.4%) versus self-report (82.0%). Top participant-identified gaps in post-treatment services were: side effect management, achieving body weight and physical activity goals, psychosocial health, and sexual health. 71.7% of participants reported that they would have used a telephone follow-up clinic. Factors associated with telephone follow-up clinic use included younger age, no endocrine therapy, fatigue, and non-urban residence. CONCLUSIONS Concordance with measurable follow-up goals (exam, mammography, endocrine therapy) was better than expected. Despite this, interest in a nurse-led BC telephone follow-up clinic was high. Perceived needs included management of symptoms plus support for life-style behavior change.