Effectiveness of 1st-line treatment options in mRCC – a German RCC-Registry evaluation Goebell, P.J.1, Müller, L.2, Lück, A.3, Overkamp, F.4, Vogt M.5, Marschner N.6 for the RCC Registry group

1Urologische Universitätsklinik im Waldkrankenhaus St. Marien, Erlangen, Germany, 2Onkologische Schwerpunktpraxis Leer Emden, Leer, Germany, 3Zentrum für Urologie und Onkologie, Rostock, Germany, 4Praxis und Tagesklinik für Onkologie, Recklinghausen, Germany, 5iOMEDICO, Freiburg, Germany, 6Praxis für interdisziplinäre Onkologie & Hämatologie, Freiburg, Germany

Introduction: nd st Over the last few years, several efficacious therapeutic options Table 1 Patients Characteristics – 1st-line Figure 1 Treatments per year – 1st-line treatment censored at the start of 2 -line therapy, end of 1 -line therapy or at last contact or last documentation. have been developed for patients with metastatic renal cell carcinoma a For those patients whose 70% Patients Characteristics Sunitinib Sorafenib Total (mRCC). Due to the variety of multiple new targeted therapeutic respective parameters have 2007 been documented. 60% a For the matched-pair analysis, patients treated with sorafenib were options head-to-head comparisons based solely on randomized Number of patients (n[%]) 555 (55.2%) 82 (8.2%) 1006 b At the start of 1st-line 2008 treatment. 2009 matched to patients treated with sunitinib and having a comparable clinical trials are lacking. Registry data complement data from Gender 50% 31.7 31.7 31.9 c The Charlson Comorbidity- 2010 (female (%)) disease-free interval. PFS was calculated for all patients who had clinical trials by providing insight into the treatment and outcome Score indicates, to what 2011 st in routine practice. However, outcome data provided by registries Age (years) b (mean value [±Std]) 67.3 [±10.5] 67.0 [±10.1] 67.4 [±10.2] extend patients are affected 40% 2012 completed 1 -line treatment. by comorbidities at the start 2013 may be skewed by many factors such as patient characteristic of 1st-line treatment. BMI b (mean value [±Std]) 26.7 [±4.3] 28.1 [±5.3] 26.9 [±4.7] 30% and comorbidities. Such factors have to be adjusted for to obtain d Time from primary diagnosis to start of 1st-line treatment. Results: meaningful analyses. Matched-pair analyses provide an interesting Motzer‘s-Score b (mean value [±Std]) 0.8 [±0.9] 0.8 [±0.9] 0.9 [±1.0] e 20% At primary diagnosis. st tool to compare the effectiveness of different treatment options. Sunitinib is the most commonly used 1 -line treatment but [0] low risk (patients, %) 42.6 41.1 38.4 10% with decreasing frequency

Methods: [1-2] intermediate risk (patients, %) 52.6 54.8 54.4 0% From 2007 to 2013, 55% of all patients recruited received sunitinib. Figure 1 demonstrates that during this time, the proportion of The open, longitudinal, multicenter, clinical registry on renal [3-5] high risk (patients, %) 4.8 4.1 7.2

Other sunitinib treatments continuously decreased. Pazopanib, approved cell carcinoma (RCC Registry, ClinicalTrials.gov registry: Charlson Comorbidity Index b,c 1.0 1.5 1.1 Sunitinib in 2010, has been used more frequently in recent years. Overall, Sorafenib

(mean value) Interleukin NCT00610012) prospectively collects data on the treatment of Pazopanib st d 8% of patients received sorafenib as 1 -line treatment.

Disease free interval (b) Interferon Temsirolimus Bevacizumab +Interferon (c) +Interferon

46.0 [±66.9] 42.9 [±58.5] 42.8 [±68.4] (a) +Interferon patients with advanced or metastatic renal cell carcinoma (mRCC) (mean value [±Std]) Number of lymph nodes affected e as administered by a network of German office-based medical 0.6 [±2.2] 1.0 [±3.4] 0.8 [±2.5] Patients receiving sunitinib and sorafenib in routine (mean value [±Std]) Observation period January 1, 2007 – November 15, 2013. Number of treatments = 1067. oncologists and uro-oncologists. Since the start of the registry a Including bevacizumab monotherapy. practice differ in December 2007, 114 sites (currently 270 oncologists and uro- Nephrectomy (patients, %) 78.0 72.0 75.6 b Interferon alpha monotherapy, Interferon alpha with and without 5-FU +/- folic acid, Interferon alpha plus vinblastine were pooled. Table 1 shows that patients treated with sorafenib are more often oncologists) have actively recruited a total of 1114 patients. c With and without 5-FU +/- folic acid. affected by comorbidities, have a shorter disease-free interval and had less often undergone nephrectomy than patients treated with Patients receive standard treatments according to physician‘s st sunitinib. choice. At time of enrolment, data on patient‘s demography, tumor Figure 2 Kaplan-Meier Curves for PFSREG – 1 -line treatment with sunitinib and sorafenib

characteristics, clinical parameters, comorbidities and previous Figure 3 Matched-Pair PFS analysis 1st-line treatment – matched for disease free interval The RCC Registry represents REG This difference in patient selection most likely affects the outcome 100% |||||| Sunitinib (n = 324) routine practice and it is treatments are documented. During the course of therapy, all | || || 30 SUN: Sunitinb | || Soraf enib (n = 38) not specified when, how seen for these two substances in routine practice. Estimated PFS systemic treatments as well as outcome parameters including date |||| often and according to SOR: Sorafenib 90% |||| for all patients is 9.0 months for sunitinib (62.7% events) and 5.9 ||| which criteria the treating of progression(s) and death are documented. Patients are followed | 25 | physician monitors the course months for sorafenib (52.6 % events, Figure 2). However, when PFS until death or for a maximum of three years. 80% || ||| of disease. The “registry is analysed for patients with similar disease-free interval (matched- | PFS” (PFS ) presented || | censored REG 20 70% should be considered the pair analysis), PFS is comparable for sunitinib and sorafenib ||| Automated plausibility and completeness checks with subsequen- || best approximation and || ||| not identical with the PFS (Figure 3). tly generated queries by the electronic data capture system ensure 60% | 15 | determined in clinical trials. | data reliability. In addition, data managers regularly check for |||| Differences in PFS | | REG 50% | between the treatments do Conclusions: plausibility and issue queries. | | 10 ||| not directly imply differences | || in effectiveness, but could 40% Registry data can be used to assess real life effectiveness of Patients with histologically confirmed mRCC can be included if they | || be due to differing patient 5 characteristics. treatments in routine practice. Differences in patient characteristics | | | || | signed informed consent no longer than 1 year after the start of 30% | The permanent black line which reflect treatment decision making, have to be considered st || marks the median. systemic 1 -line treatment. Outcome data, such as progression-free | || | 0 when such analyses are performed. When patient numbers are 20% || time to progression/ death [months] survival (PFS) are analysed for all patients who signed informed Patientsalive without progression(first-line) || | not sufficient for multivariate regression models, matched-pair st || consent no longer than six weeks after the start of 1 -line treatment. | | -5 10% | | analyses can be used to adjust to differences in characteristics. The restriction is important to avoid an overestimation of outcome | | | | | SUN SOR data. 0% median 25%-75% area without outlier Registry data can be used to perform head-to-head comparisons 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 outliers of treatments and thereby generate hypothesis into their effective- PFS was estimated with the Kaplan-Meier method. Patients alive Progression-f ree surv iv al f irst-line [months] ness in routine practice. Randomised controlled trials would be or lost to follow-up were censored at last contact or last docu- desirable to validate such results. mentation. Patients without progression under 1st-line therapy were

Acknowledgement: The RCC Registry group thanks all patients participating in the RCC-Registry. The Registry is conducted by iOMEDICO in collaboration with the Arbeitskreis Klinische Studien in onkologischen und hämatologischen Praxen e.V. as well as the Bund der Urologen e.G. The registry is funded by iOMEDICO. iOMEDICO has received grants for the Registry from ASCO GU San Francisco 2014 Bayer Vital GmbH, GlaxoSmithKline GmbH & Co. KG, Novartis Pharma GmbH, Pfizer Pharma GmbH and Roche Pharma AG. Abstract Number: 429