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The NASA Double Asteroid Redirection Test (DART) mission performed a kinetic impact on asteroid Dimorphos, the satellite of the binary asteroid (65803) Didymos, at 23:14 UTC on September 26, 2022 as a planetary defense test. DART was the first hypervelocity impact experiment on an asteroid at size and velocity scales relevant to planetary defense, intended to validate kinetic impact as a means of asteroid deflection. Here we report the first determination of the momentum transferred to an asteroid by kinetic impact. Based on the change in the binary orbit period, we find an instantaneous reduction in Dimorphos's along-track orbital velocity component of 2.70 +/- 0.10 mm/s, indicating enhanced momentum transfer due to recoil from ejecta streams produced by the impact. For a Dimorphos bulk density range of 1,500 to 3,300 kg/m$^3$, we find that the expected value of the momentum enhancement factor, $\beta$, ranges between 2.2 and 4.9, depending on the mass of Dimorphos. If Dimorphos and Didymos are assumed to have equal densities of 2,400 kg/m$^3$, $\beta$= 3.61 +0.19/-0.25 (1 $\sigma$). These $\beta$ values indicate that significantly more momentum was transferred to Dimorphos from the escaping impact ejecta than was incident with DART. Therefore, the DART kinetic impact was highly effective in deflecting the asteroid Dimorphos., Comment: accepted by Nature

Given the numerous possibilities that formation flying space missions can enable, being able to design and govern relative trajectories in this scenario is fundamental. Particularly interesting, due to the installation and operation of the Lunar Gateway, which will represent the next human outpost in the cislunar environment, will be the exploitation of formation flying missions in the vicinity of this lunar station. The nonlinear dynamics by which the Earth-Moon system is characterised offers the possibility to find bounded relative trajectories which can be used to design the formation. In order to best exploit the formation potential, some reconfiguration manoeuvres can be used, which by changing the relative geometry can increase the versatility and adaptation of the mission. In this paper, a Model Predictive Guidance and Control strategy is proposed and applied to perform rephasing manoeuvres in the harsh environment of the Near Rectilinear Halo Orbits. By including first a limited thrust constraint and then a collision avoidance, a more mission-oriented approach is provided to the system. To further increase the robustness of the on-board algorithms, an adaptive logic is provided to the different tuning weights involved in the Model Predictive Control scheme. In this way, a more flexible system is obtained, which is capable of optimally working also in the presence of a high-fidelity simulation scenario, including discrepancies with the simplified on-board dynamical model.

Aim: Assessing treatment patterns, outcomes and clinical characteristics in advanced renal cell carcinoma clinical practice. Materials & methods: A US cross-sectional physician survey conducted February–September 2019. Results: Surveyed physicians reported first-line treatment of 445 patients involving tyrosine kinase inhibitor monotherapy (51.0%), immuno-oncology (IO/IO combination) therapy (25.8%) or other regimens (23.1%). A total of 60.9% had physician-assessed IMDC risk. Of these 61.9, 50.9 and 27.6% of patients with favorable, intermediate and poor risk, respectively, received tyrosine kinase inhibitor monotherapy. A total of 16.7, 26.9 and 34.5% of patients with favorable, intermediate or poor risk received IO/IO combination therapy. Complete/partial responses (∼35% patients) remained comparable across first-line treatments. Conclusion: Guideline-recommended therapies are not widely prescribed. Many patients experienced poor clinical outcomes highlighting a need for more effective treatments.

Light Italian Cubesat for Imaging of Asteroids (LICIACube) is an Italian mission managed by the Italian Space Agency (ASI) and part of the NASA Double Asteroid Redirection Test (DART) planetary defense mission. Its main goals are to document the effects of the DART impact on Dimorphos, the secondary member of the (65803) Didymos binary asteroid system, characterizing the shape of the target body and performing dedicated scientific investigations on it. Within this framework, the mission Science Operations Center will be managed by the Space Science Data Center (ASI-SSDC), which will have the responsibility of processing, archiving, and disseminating the data acquired by the two LICIACube onboard cameras. In order to better accomplish this task, SSDC also plans to use and modify its scientific webtool Multi-purpose Advanced Tool for Instruments for the solar system Exploration (MATISSE), making it the primary tool for the LICIACube data analysis, thanks to its advanced capabilities for searching and visualizing data, particularly useful for the irregular shapes common to several small bodies.

The Light Italian Cubesat for Imaging of Asteroids (LICIACube) is part of the NASA Double Asteroid Redirection Test (DART), the first mission aiming to demonstrate the applicability of the kinetic impactor method for planetary defense. The mission was launched on 2021 November 24 to perform the impact experiment on Dimorphos, the small secondary of the binary asteroid (65803) Didymos. The 6U LICIACube, stored as a piggyback of the DART spacecraft, is the first Italian mission operating in deep space managed by the Italian Space Agency that will witness the effects of the DART impact on Dimorphos. On board LICIACube, there is a suite of cameras that will perform imaging of Didymos and Dimorphos to investigate the DART impact effects and study the binary system. Among them, the LICIACube Unit Key Explorer (LUKE), a wide-angle camera coupled to an RGB Bayer pattern filter, will be pivotal to constrain the surface composition and heterogeneity of the binary system due to differences in surface properties linked with possible space weathering effects and/or the presence of exogenous material. Multiband photometric analysis of LUKE data and laboratory experiments in support of data interpretation will provide new insights on the binary asteroid nature and evolution. Moreover, photometric phase curve analysis will reveal the scattering properties of the granular surface medium providing important constraints for the microphysical properties of the Didymos–Dimorphos system. In this work, we will present the state of the art of the LUKE scientific activities with an overview of the instrument setup, science operations, and expected results.

Background It is unclear whether patients with renal cell carcinoma (RCC) are routinely assessed for recurrence risk post‐nephrectomy and whether patients at high recurrence risk are seen by providers who can evaluate candidacy for adjuvant systemic therapy (AST) and clinical trials. Materials and Methods We identified all patients with locoregional RCC who underwent nephrectomy via an institutional database within Duke University Health System between 1 April 2015 and 31 December 2019. Medical records were reviewed to identify patient characteristics, post‐nephrectomy referrals, treatment, and follow‐up. Patients with tumor stage ≥3 and grade ≥2, regional lymph node metastasis, or both, were classified as high recurrence risk. Results Of 618 patients with locoregional RCC who underwent nephrectomy, 136 (22%) had high recurrence risk. Of those, 25 patients with high‐risk disease (18%) were referred to medical oncology for discussion of AST; 23 (92%) of these referrals took place in 2018–2019. One patient received adjuvant sunitinib and two patients participated in adjuvant immunotherapy trials. The decision not to receive AST was primarily made by the oncologist in 10 (46%), the patient in 8 (36%), and unrecorded in 4 (18%) of 22 cases, for multiple reasons. Individual surgeons referred high‐risk patients for discussion of AST with varying frequency, ranging from 0% to 100% in 2019. Conclusions Despite increasing number of patients with locoregional RCC at high recurrence risk referred to medical oncologists after nephrectomy, few patients received AST, including participation in clinical trials. With increasing AST options and ongoing clinical trials in this space, these findings highlight the need for continued efforts at identifying effective AST and referring patients most likely to benefit to medical oncologists. ClinicalTrials.gov, NCT04309617., We identified all patients with locoregional renal cell carcinoma who underwent nephrectomy between 1 April 2015 and 31 December 2019 to characterize patient characteristics, patients at high recurrence risk, post‐nephrectomy referrals, treatment, and follow‐up. Despite increasing number of patients with locoregional RCC at high recurrence risk referred to medical oncologists after nephrectomy (23 of 25 referrals taking place in 2018‐2019), few patients (n=3) received adjuvant systemic therapy, including participation in clinical trials.

Background International Metastatic Renal Cell Carcinoma (mRCC) Database Consortium (IMDC) risk groups are important when considering therapeutic options for first-line treatment. Materials and Methods Adult patients with clear cell mRCC initiating first-line sunitinib between 2010 and 2018 were included in this retrospective database study. Median time to treatment discontinuation (TTD) and overall survival (OS) were estimated using Kaplan-Meier analysis. Outcomes were stratified by IMDC risk groups and evaluated for those in the combined intermediate and poor risk group and separately for those in the intermediate risk group with one versus two risk factors. Results Among 1,769 patients treated with first-line sunitinib, 318 (18%) had favorable, 1,031 (58%) had intermediate, and 420 (24%) had poor IMDC risk. Across the three risk groups, patients had similar age, gender, and sunitinib initiation year. Median TTD was 15.0, 8.5, and 4.2 months in the favorable, intermediate, and poor risk groups, respectively, and 7.1 months in the combined intermediate and poor risk group. Median OS was 52.1, 31.5, and 9.8 months in the favorable, intermediate, and poor risk groups, respectively, and 23.2 months in the combined intermediate and poor risk group. Median OS (35.1 vs. 21.9 months) and TTD (10.3 vs. 6.6 months) were significantly different between intermediate risk patients with one versus two risk factors. Conclusion This real-world study found a median OS of 52 months for patients with favorable IMDC risk treated with first-line sunitinib, setting a new benchmark on clinical outcomes of clear cell mRCC. Analysis of intermediate risk group by one or two risk factors demonstrated distinct clinical outcomes. Implications for Practice This analysis offers a contemporary benchmark for overall survival (median, 52.1 months; 95% confidence interval, 43.4–61.2) among patients with clear cell metastatic renal cell carcinoma who were treated with sunitinib as first-line therapy in a real-world setting and classified as favorable risk according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group classification. This study demonstrates that clinical outcomes differ between IMDC risk groups as well as within the intermediate risk group based on the number of risk factors, thus warranting further consideration of risk group when counseling patients about therapeutic options and designing clinical trials.

The optimal dosing schedule to maintain the effectiveness of sunitinib for metastatic renal cell carcinoma – while reducing toxicity – remains an important clinical question. A meta-analysis of randomized trials and observational studies assessed the relative treatment effects of 4/2, 2/1 and transitional-2/1 schedules on outcomes and adverse events using Bayesian network meta-analysis methods. Treatment with 2/1 reduced the risk of disease progression or death by 25% and had lower odds of hand-and-foot syndrome compared with the 4/2. A numerical but not ‘statistical’ benefit in progression-free survival was observed with the transitional-2/1 compared with 4/2. Alternative schedules with the 2/1 and transitional-2/1 may be more clinically beneficial in metastatic renal cell carcinoma than the 4/2 schedule.

Um tema clássico na interpretação de Hegel é o da relação entre “método” e “sistema”, elementos formais e estruturais, por um lado, e conteúdos particulares, por outro. Esse problema adquire uma relevância especial nas tentativas de crítica filosófica: se em Hegel há algo falso, o erro é de método, de conteúdo, ou ambos? Neste artigo são examinadas duas críticas exemplares à dialética hegeliana, a do jovem Marx na Crítica de 1843 e nos Manuscritos econômico-filosóficos, e a de Adorno nos Três estudos sobre Hegel e na Dialética negativa. As duas convergem na premissa – a reivindicação do momento objetivo na subjetividade – e na conclusão – a denúncia do caráter apologético da filosofia hegeliana. Contudo, enquanto a tese marxiana de uma redução, em Hegel, da objetividade à “consciência-de-si” não consegue, em última análise, dar conta da estrutura geral do idealismo objetivo hegeliano, mas apenas de algumas contradições específicas no sistema, a estratégia adorniana de uma dialética da identidade mostra-se mais adequada à exigência de uma crítica do método hegeliano como crítica imanente.

BACKGROUND: Immuno-oncology (IO) therapies have changed the treatment standards of metastatic renal cell carcinoma (mRCC). However, the effectiveness of targeted therapy following discontinuation of IO therapy in real-world settings has not been well studied.OBJECTIVE: To describe treatment sequence and assess clinical effectiveness of targeted therapy for mRCC patients who received prior IO therapy.DESIGN, SETTING, AND PARTICIPANTS: A retrospective, longitudinal cohort study using data from eight international cancer centers was conducted. Patients with mRCC were ≥18yr old, received IO therapy in any line, and initiated targeted therapy following IO therapy discontinuation.INTERVENTION: Patients were treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) or mammalian target of rapamycin inhibitors (mTORIs).OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were time to treatment discontinuation (TTD), overall survival (OS), and objective response rate (ORR). Crude and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. Models were adjusted for age, sex, therapy line, and International Metastatic RCC Database Consortium risk group.RESULTS AND LIMITATIONS: Among 314 patients, 276 (87.9%) and 38 (12.1%) were treated with VEGFR-TKI and mTORI therapy, respectively. The most common tyrosine kinase inhibitor treatments were axitinib, cabozantinib, and sunitinib following IO therapy. In adjusted models, patients treated with VEGFR-TKI versus mTORI therapy had lower hazard of TTD after IO treatment (aHR=0.46; 95% CI: 0.30-0.71; p < 0.01). One-year OS probability (65% vs 47%, p < 0.01) and proportion of ORR (29.8% vs 3.6%, p < 0.01) were significantly greater for patients treated with VEGFR-TKIs versus those treated with mTORIs.CONCLUSIONS: Targeted therapy has clinical activity following IO treatment. Patients who received VEGFR-TKIs versus mTORIs following IO therapy had improved clinical outcomes. These findings may help inform treatment guidelines and clinical practice for patients post-IO therapy.PATIENT SUMMARY: Patients may continue to experience clinical benefits from targeted therapies after progression on immuno-oncology treatment.

HERMES-TP/SP (High Energy Rapid Modular Ensemble of Satellites Technologic and Scientific Pathfinder) is a constellation of six 3U nano-satellites hosting simple but innovative X-ray detectors, characterized by a large energy band and excellent temporal resolution, and thus optimized for the monitoring of Cosmic High Energy transients such as Gamma Ray Bursts and the electromagnetic counterparts of Gravitational Wave Events, and for the determination of their positions. The projects are funded by the Italian Ministry of University and Research and by the Italian Space Agency, and by the European Union Horizon 2020 Research and Innovation Program under Grant Agreement No. 821896. HERMES-TP/SP is an in-orbit demonstration, that should be tested starting from 2022. It is intrinsically a modular experiment that can be naturally expanded to provide a global, sensitive all sky monitor for high-energy transients., Comment: 15 pages, 3 figures, Proceedings of SPIE Astronomical Telescopes and Instrumentation 2020

The HERMES-TP/SP (High Energy Rapid Modular Ensemble of Satellites -- Technologic and Scientific Pathfinder) is an in-orbit demonstration of the so-called distributed astronomy concept. Conceived as a mini-constellation of six 3U nano-satellites hosting a new miniaturized detector, HERMES-TP/SP aims at the detection and accurate localisation of bright high-energy transients such as Gamma-Ray Bursts. The large energy band, the excellent temporal resolution and the wide field of view that characterize the detectors of the constellation represent the key features for the next generation high-energy all-sky monitor with good localisation capabilities that will play a pivotal role in the future of Multi-messenger Astronomy. In this work, we will describe in detail the temporal techniques that allow the localisation of bright transient events taking advantage of their almost simultaneous observation by spatially spaced detectors. Moreover, we will quantitatively discuss the all-sky monitor capabilities of the HERMES Pathfinder as well as its achievable accuracies on the localisation of the detected Gamma-Ray Bursts., 19 pages, 13 figures, Proceedings of SPIE Astronomical Telescopes and Instrumentation 2020

Objectives: Scant research exists on evolving real world treatment patterns given new immuno-oncology (IO) combination regimens added to the National Comprehensive Cancer Network (NCCN) guidelines for advanced renal cell carcinoma (aRCC) This study describes real-world (RW) treatment patterns in a large US claims database toward understanding new standards of care in aRCC treatment Methods: Using Optum Clinformatics Claims data, patients ≥18 with ≥ 2 RCC diagnoses 30-days apart, who subsequently start first-line (1L) aRCC treatment (study index date) during April 2018 to March 2019 were all followed-for 9 months Patients had ≥2 secondary malignancy codes in the 12 months prior/30 days post-index date and 9-months of continuous enrollment pre- and post-index Results: Study identified 415 1L aRCC patients The most common 1L regimen was monotherapy tyrosine kinase inhibitors (mono TKIs) representing 43 13% (N=179) Combination IO (combo IO), monotherapy IO (mono IO), IO + TKI, and Other, represented 28 43% (N=118), 25 30% (N=105), 0 96% (N=4) and 3 13% (N=13) respectively Combo IO patients were younger, mean age 66 58, compared to mono TKI and mono IO patients, mean age 70 15 (p=0 003) and 72 72 (p

Aim: To understand the treatment patterns and outcomes for stage IV squamous cell carcinoma of the head and neck, patients receiving second-line or later drug therapy. Materials & methods: Real-world data were collected from 1152 patients in the USA, France, Germany and the UK through a retrospective chart analysis and patient-reported outcomes were collected using validated questionnaires in a subgroup of patients. Results: Forty-four percent of patients had stage IVA/B disease. A total of 77, 19 and 3% of patients had received two, three and four plus lines of active drug treatment. Platinum- and cetuximab-based regimens were common at early treatment lines. Time to progression was short (5.2 months post first line), survival rates low and patient-reported health status poor. Conclusion: Novel therapies that could improve clinical and patient-reported outcomes would address a significant unmet need.

Advanced breast cancer (abc) represents a substantial burden for patients and caregivers. In the present study, we aimed to estimate quality of life (qol), utility, productivity loss, pain, health care resource utilization, and costs for patients with abc, and qol, utility, and productivity loss for their caregivers. This multicentre prospective non-interventional study was conducted in Canada. Eligible participants were postmenopausal women with estrogen receptor&ndash, positive, her2-negative unresectable abc and their caregivers. Validated questionnaires were used to measure qol, utility, productivity loss, and pain. Patients and caregivers were classified into 4 health states typically used in oncology economic modelling: first-line progression-free (1l-pf), first-line progressive disease (1l-pd), second- or subsequent-line progression-free (&ge, 2l-pf), and second- or subsequent-line progressive disease (&ge, 2l-pd). Most patients and caregivers accepted to participate, with total recruitment of 202 patients and 78 caregivers. Compared with patients in pf, patients in pd had lower mean qol scores (52.9 &plusmn, 29.9 for 1l-pd vs. 68.2 &plusmn, 23.2 for 1l-pf, and 54.0 &plusmn, 23.6 for &ge, 2l-pd vs. 66.0 &plusmn, 22.1 for &ge, 2l-pf), lower mean utility values (0.64 &plusmn, 0.22 for 1l-pd vs. 0.73 &plusmn, 0.20 for 1l-pf, and 0.65 &plusmn, 0.25 for &ge, 2l-pd vs. 0.74 &plusmn, 0.18 for &ge, 2l-pf), and greater productivity loss (39.4 &plusmn, 27.7 for 1l-pd vs. 27.5 &plusmn, 30.1 for 1l-pf, and 37.6 &plusmn, 29.2 for &ge, 2l-pd vs. 32.0 &plusmn, 29.0 for &ge, 2l-pf). Compared with caregivers of patients in pf, caregivers of patients in pd had lower qol scores and utility values, and greater productivity loss. Study results indicate that, for patients and caregivers, pd health states are associated with a deterioration of qol and utility and a decrease in productivity in both 1l and &ge, 2l.

Purpose To describe treatment patterns and clinical outcomes among postmenopausal women with metastatic ER+/HER-2− breast cancer treated with ≥ 2 lines of endocrine therapy or chemotherapy in the metastatic setting. Patients and Methods Retrospective medical record review was conducted in Canada, the United Kingdom, Belgium, the Netherlands, Germany, Spain, and France. Baseline characteristics were assessed at the date of metastatic diagnosis. Time to progression (TTP) and overall survival (OS) were estimated by Kaplan-Meier analyses. Multivariable models were used to evaluate factors associated with disease progression. Results Among 901 patients, the mean (standard deviation) age at metastatic diagnosis was 62.7 (9.7) years; 67.26% were initially diagnosed with metastatic disease, 66.37% had visceral disease, and 25.86% had bone metastasis only. Two-thirds of patients received endocrine therapy for first-line treatment. Fifty-nine percent received endocrine therapy, and 37.18% received chemotherapy for second-line treatment. The most common reason for stopping treatment was disease progression. Median (95% confidence interval [CI]) TTP on first-line endocrine treatment was 11.3 (10.7-12.2) months and 7.0 (6.3-7.9) months on chemotherapy. Median (95% CI) TTP on second-line endocrine therapy was 8.1 (7.5-9.1) months and 6.1 (5.4-6.8) months on chemotherapy. Median (95% CI) OS was 68.6 (52.2-83.7) months after first-line endocrine therapy and 39.7 (34.5-48.7) months after chemotherapy. Conclusion Patients prescribed endocrine therapy had longer TTP and OS than patients prescribed chemotherapy in the first- and second-line settings. Disease progression was less than a year regardless of treatment type and line of therapy, indicating a need for treatments that delay progression without affecting quality of life among these patients.

Background Rapidly evolving understanding of cancer biology has presented novel opportunities to translate that understanding into clinically relevant therapy. Palbociclib, a novel, first-in-class cyclin-dependent kinase (CDK) 4/6 inhibitor was approved in the USA in February 2015 for the treatment of advanced/metastatic breast cancer. We examined real-world evidence in the first year post approval to understand the clinical and demographic characteristics of patients treated with palbociclib in community oncology practices and the dosing, treatment, and complete blood count (CBC) monitoring patterns. Methods This was a retrospective observational study of structured data from a US electronic medical record (EMR) database. Female patients receiving palbociclib after 31 January 2015 were followed through 31 March 2016. Our methodological rules were constructed to aggregate drugs received according to the order in which they are given, i.e., identify the line of therapy as first, second, or third line, etc., using treatment order and course description fields from the EMR. Results There were 763 patients initiating palbociclib who met the selection criteria. Of those, 612 (80.2%) received palbociclib concomitantly with letrozole. Mean follow up was 6.4 months and mean age at palbociclib initiation was 64 years. Of patients with a known starting dose (n = 417), 79.9% started on palbociclib 125 mg. Dose reductions were observed in 20.1% of patients. Percentages of patients according to line of therapy at initiation of palbociclib were first-line, 39.5%; second-line, 15.7%; third-line, 13.1%; and fourth-line therapy or later, 31.7%. On average, two CBC tests were conducted during the first cycle of palbociclib treatment. Overall, 74.6% of patients had a neutropenic event during follow up including 47.3% and 8.0% of patients with a grade 3 or 4 occurrence, respectively. Conclusions Real-world palbociclib use one year post US approval demonstrates a more heterogeneous patient population than that studied in the clinical trials with more than half of the patients receiving palbociclib plus letrozole in later lines of therapy. CBC testing rates suggested good provider compliance with monitoring guidelines in the USA prescribing information. The occurrence of grade 3 and 4 neutropenia (based on laboratory results) was consistent with the rates of grade 3 and 4 neutropenia in two phase-III studies (PALOMA-2, 56% and 10%; PALOMA-3, 55% and 11%, respectively). Understanding palbociclib utilization in real-world patients and how drug dosing and monitoring are performed aids in the understanding of safe and effective use of the drug. Electronic supplementary material The online version of this article (10.1186/s13058-018-0958-2) contains supplementary material, which is available to authorized users.

314 Background: The combination of axitinib plus pembrolizumab (AXI+PEM) is a standard of care in the first-line (1L) treatment of patients with advanced clear cell renal cell carcinoma (RCC). This analysis describes the demographic and clinical characteristics, treatment and outcomes of patients receiving 1L AXI+PEM in a real-world setting. Methods: Medical record data were extracted from the Flatiron Health Database, which includes ̃280 cancer clinics across 800 sites in the US. Patients had confirmed Stage IV or metastatic RCC and initiated 1L AXI+PEM on or after 1/1/2018 to 3/31/2021. Tumor response is reported as best overall response to 1L therapy; real-world progression-free survival (rwPFS) and overall survival (rwOS) are reported as patients without a clinical event (rwPFS; progression/death; rwOS; death) at landmark time periods (3, 6, 9, and 12 months); denominators include censored patients. Other data are reported as medians (min, max) unless otherwise noted. Results: Three hundred and fifty-five patients received 1L AXI+PEM, with follow-up of 9.7 (0.1–24.3) months. Most patients were male (69.6%), and age was 68.0 (21.0–84.0) years. At diagnosis, 55.5% of patients had Stage IV RCC and 77.2% of patients had clear cell histology. IMDC Risk Score was favorable, intermediate, and poor in 27 (7.6%), 126 (35.5%), and 76 (24.4%) patients, respectively. At the time of analysis, 270 patients (76.1%) received only 1L therapy with AXI+PEM, while 85 patients (24.3%) received ≥1 subsequent line of treatment. VEGF-R inhibitors were the most commonly used second-line (2L) treatment (51 patients, 60.0%), with cabozantinib as the most frequently used VEGF-R inhibitor (40 patients, 47.1%). rwPFS at 3 months and 1 year was achieved by 248 patients (69.9%) and 77 patients (21.7%), respectively. rwOS ranged from 293 patients (82.5%) surviving at 3 months to 142 patients (40.0%) surviving at 1 year. Best overall response rate to 1L was 47.9% (complete or partial response observed in 170/355 patients). Conclusions: This study provides real-world evidence for the use and effectiveness of 1L AXI+PEM in patients with advanced RCC. AXI+PEM was used across all IMDC risk groups. While these initial finding support the use of AXI+PEM, additional follow-up is warranted to provide further understanding of the clinical outcomes and treatment patterns of patients with advanced RCC in the US receiving 1L AXI+PEM.

HERMES (High Energy Rapid Modular Ensemble of Satellites) Technological and Scientific pathfinder is a space borne mission based on a LEO constellation of nano-satellites. The 3U CubeSat buses host new miniaturized detectors to probe the temporal emission of bright high-energy transients such as Gamma-Ray Bursts (GRBs). Fast transient localization, in a field of view of several steradians and with arcmin-level accuracy, is gained by comparing time delays among the same event detection epochs occurred on at least 3 nano-satellites. With a launch date in 2022, HERMES transient monitoring represents a keystone capability to complement the next generation of gravitational wave experiments. In this paper we will illustrate the HERMES payload design, highlighting the technical solutions adopted to allow a wide-energy-band and sensitive X-ray and gamma-ray detector to be accommodated in a CubeSat 1U volume together with its complete control electronics and data handling system., Comment: 12 pages, 13 figures. Proceedings of SPIE "Astronomical Telescopes and Instrumentation" 2020

BACKGROUND: The present retrospective, longitudinal cohort study assessed the association between the first-line sunitinib treatment duration and clinical outcomes with second-line immuno-oncology (IO) therapy among patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: A total of 161 patients with mRCC who had been treated with first-line sunitinib and subsequent IO therapy from select International mRCC Database Consortium centers were included. The overall survival, time to next therapy, time to treatment discontinuation, and real-world physician-assessed best response measured from IO therapy initiation were analyzed and compared between patients treated with first-line sunitinib for ≥ 6 months and those treated for < 6 months. RESULTS: The 116 patients treated with sunitinib for ≥ 6 months tended to be older and to have a better International mRCC Database Consortium risk than the 45 patients treated for < 6 months (favorable, 36% vs. 8%, P = .001; intermediate, 59% vs. 70%, P = .21; poor, 5% vs. 22%, P = .007). The receipt of sunitinib for ≥ 6 months versus < 6 months was associated with longer survival (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.21-0.87; P = .02). No significant association was observed between the first-line sunitinib duration and second-line IO outcomes, including the time to next therapy (HR, 0.89; 95% CI, 0.52-1.51; P = .66), time to treatment discontinuation (HR, 0.85; 95% CI, 0.54-1.34; P = .49), and tumor response (odds ratio, 0.73; 95% CI, 0.22-2.49; P = .62). CONCLUSIONS: We found no statistically significant association between the first-line sunitinib duration and clinical outcomes with second-line IO therapy. Patients receiving first-line sunitinib for ≥ 6 months compared with < 6 months was associated with better overall survival, although potential unadjusted confounders could have been present. These findings support the paradigm that previous therapy will not dictate the effectiveness of subsequent immunotherapy. ispartof: CLINICAL GENITOURINARY CANCER vol:18 issue:4 pages:E350-E359 ispartof: location:United States status: published

Objectives This study developed, and established the content validity, of a conversation aid tool (CAT) for use in clinical practice with renal cell carcinoma (RCC) patients who receive a curative nephrectomy and are at high-risk of recurrence. The CAT was pilot tested in a sample of RCC patients to establish whether the CAT increases knowledge of RCC, treatment options (such as adjuvant therapy), and care options. Methods A cross-sectional, mixed methods design was used involving initial, exploratory interviews with RCC patients, RCC specialists and a steering group. Further content validation interviews were conducted with RCC patients and specialists. A web-based survey was conducted with RCC patients (N = 60), to compare the CAT versus a standard of care (SOC) consultation comparator tool on patient knowledge. Results Findings from exploratory interviews were used to develop the CAT. Content validation interviews demonstrated that the CAT was well understood and relevant to RCC patients. The web-based survey demonstrated that viewing the CAT significantly improved participants knowledge of RCC, and care options, when compared to the SOC. Conclusion The findings highlight that the CAT is a relevant, comprehensive and well-understood tool for use in the post-nephrectomy consultation. Practice implications Use of the CAT may increase patient knowledge of RCC and care options.

Background Palbociclib was approved in the U.S. in February 2015 for the treatment of advanced/metastatic breast cancer (MBC) in combination with letrozole as initial endocrine based therapy for post-menopausal women with ER+/HER2- disease. We examined the demographic, clinical characteristics and treatment patterns of patients initiating palbociclib (PAL) + letrozole (LET) in real-world, community oncology practices. Methods This was a retrospective observational study of female breast cancer patients identified in the Navigating Cancer (NC) EMR database. The NC database collects EMR data, in both structured and unstructured fields (patient/clinical progress notes), from over 975 oncology and hematology providers across more than 50 locations in 25 states. Female patients with record of treatment with PAL after 01/31/2015 were selected. Combination treatment with LET was defined as having a record for LET within 30 days of the PAL prescription. Line of therapy (LOT) was assessed from the date of metastatic diagnosis and assigned by evaluating treatment plans pre-and post PAL initiation. Bi-monthly cohorts were constructed based on the month of initiation of PAL from 02/01/2015-01/31/2016. Interim results are presented; data from an additional three months of follow-up (through 03/31/2016) are pending. Results Overall, 931 unique patients were identified as having initiated PAL treatment. Of those, 608 (65.3%) received PAL + LET. Mean follow-up was relatively short at 5.4 mo (SD=3.5). Confirmed ER+/HER2- was observed in 71.6% of patients and 50.3% were age ≥65, mean age was 64.3 yrs. Of patients with available ECOG-PS at treatment initiation (n=424): 0/1=78.5%, 2=17.5% and 3=4.0%. Of patients with a known starting dose (n=418), 69.9% initiated with PAL 125mg, 22.0% at 100mg and 8.1% at 75mg. Compared to women < 65, women ≥ 65 were more often started with 100mg (25.4% vs. 18.9%) and 75mg (10.0% vs 6.5%). Any dose reductions were observed in 20.6% of patients (21.5% of patients receiving 125mg). During the year following approval, 39.8% of patients initiated PAL + LET at LOT1, 15.6% at LOT2, 13.0% at LOT3 and 31.6% at LOT4+, following MBC diagnosis. Over time the proportion of late use (LOT4+) declined from 39.7% in Feb/Mar '15 to 23.9% in Dec '15/Jan '16 with more patients utilizing in LOT3 (from 7.9% in Feb/Mar '15 to 19.5% in Dec '15/Jan '16). Number of Patients Initiating PAL + LET by LOT and Month. AllFeb/Mar '15Apr/May '15Jun/Jul '15Aug/Sep '15Oct/Nov '15Dec'15/Jan '16N (%)608(100)63(10.4)108(17.8)125(20.6)108(17.8)91(14.5)113(18.6)LOT1 (%)242(39.8)23(36.5)45(41.7)53(42.4)45(41.7)33(36.3)43(38.1)LOT2 (%)95(15.6)10(15.9)12(11.1)19(15.2)15(13.9)18(19.8)21(18.6)LOT3 (%)79(13.0)5(7.9)10(9.3)18(14.4)12(11.1)12(13.2)22(19.5)LOT4+ (%)192(31.6)25(39.7)41(38.0)35(28.0)36(33.3)28(30.8)27(23.9) Conclusions There was a trend toward earlier utilization of PAL + LET from Feb-Jul '15, an increase in later use during Aug/Sep '15, and a return towards earlier use in subsequent cohorts reaching the lowest proportion of LOT 4+ use observed in Dec '15/Jan '16. After a mean follow-up of 5.4 mo, 21.5% of patients receiving the 125 mg dose had a dose reduction. Final results, with additional follow-up, will be presented at conference. Citation Format: Kish JK, Ward MA, Garofalo D, Ahmed HV, McRoy L, Laney J, Zanotti G, Yu H-T, Feinberg BA. Early utilization pattern of palbociclib 1 year post-approval in the United States [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-16-05.

This article examines some aspects of Adorno’s materialist dialectic, by focussing especially on hisHegel: Three Studies. While Adorno’s philosophy is commonly read ”“ both by Habermasian criticsand more sympathetic readers ”“ as a “critique of instrumental reason” aiming at a mere refutation ofHegel’s subject-object identity thesis, it is suggested here that this thesis plays a crucial role in Adornoas a dialectical moment. First Adorno’s view of the objective essence of dialectics is outlined,implying that materialist elements are already present in Hegel himself. The trascendent possibility ofutopia must be conceived, therefore, as a “real possibility”, grounded in the structure of immanentexperience. Then the question is posed of what, according to Adorno, is actually false in Hegel.Through a survey on some core concepts of negative dialectics ”“ the ontological proof of God’sexistence, the object’s preponderance, the contingency of antagonism, the historical genesis of theFreudian ego ”“ it is shown that Adorno’s critique to Hegel is directed at the idealist ontologization oflabor, and therefore, of subject ”“ itself a form of labor. Finally, a possible pratical outcome of negativedialectics is briefly hinted at, consisting in the overcoming of labor through labor, i.e., in a conceptionof the abolition of the commodity form that is dialectical, negative, and based on the acceptance of therule of law., Esse artigo investiga alguns aspectos da dialética materialista de Adorno, com particular atenção a seus Três Estudos sobre Hegel. Enquanto a filosofia de Adorno é lida frequentemente ”“ tanto por críticos habermasianos quanto por leitores mais favoráveis ”“ como uma “crítica da razão instrumental” visando uma mera refutação da tese hegeliana da identidade sujeito-objeto, é sugerido aqui que essa tese desenvolve um papel crucial em Adorno enquanto momento dialético. Em primeiro lugar, é esboçada a visão adorniana da essência objetiva da dialética, implicando que elementos materialistas já estão presentes no próprio Hegel. A possibilidade transcendente da utopia deve ser concebida, portanto, como uma “possibilidade real” fundada na estrutura da experiência imanente. Em seguida, é posta a questão de qual seria, segundo Adorno, o elemento efetivamente falso em Hegel. Através de um exame de alguns conceitos centrais da dialética negativa ”“ a prova ontológica da existência de Deus, o primado do objeto, a contingência do antagonismo, a gênese histórica do Eu freudiano ”“ mostra-se que a crítica adorniana de Hegel é dirigida à ontologização idealista do trabalho, e, portanto, do sujeito ”“ que é, por sua vez, uma forma de trabalho. Finalmente, aponta-se brevemente para um possível resultado prático da dialética negativa, que consistiria na superação do trabalho através do trabalho, ou seja, em uma concepção da abolição da forma-mercadoria que seja dialética, negativa e baseada na aceitação do Estado de direito.

In this paper I reconstruct Adorno’s arguments against the phenomenological project as developed by Husserl in the early phase of his thought, with particular focus on the dialectical nature and meaning of such a critique. Primary references are Adorno’s article Husserl and the Problem of Idealism, published in 1940, and his book Against Epistemology: A Metacritique, published in 1956. I argue that, for Adorno, Husserl’s attempt must be understood as both logically impossible and theoretically productive. After laying down the general framework of Adorno’s reading in the first three sections, I examine his criticism of Husserl’s “involuntary dialectic” in detail, also with the help of an independent analysis of some ambiguities in Husserl’s concept of “categorial intuition”. In the last section, I explain why and under what conditions, according to Adorno, the original impulse of Husserlian phenomenology toward an intact knowledge of “things themselves” needs to be maintained in spite of all.

Background: Adjuvant sunitinib has significantly improved disease-free survival versus placebo in patients with renal cell carcinoma at high risk of recurrence post-nephrectomy (hazard ratio 0.76; 95% confidence interval, 0.59-0.98; two-sided P = 0.03). We report safety, therapy management, and patient-reported outcomes for patients receiving sunitinib and placebo in the S-TRAC trial.Patients and methods: Patients were stratified by the University of California, Los Angeles Integrated Staging System and Eastern Cooperative Oncology Group performance status score, and randomized (1 : 1) to receive sunitinib (50 mg/day) or placebo. Single dose reductions to 37.5 mg, dose delays, and dose interruptions were used to manage adverse events (AEs). Patients' health-related quality of life, including key symptoms typically associated with sunitinib, were evaluated with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).Results: Patients maintained treatment for 9.5 (mean, SD 4.4) and 10.3 (mean, SD 3.7) months in the sunitinib and placebo arms, respectively. In the sunitinib arm, key AEs occurred ∼1 month (median) after start of treatment and resolved within ∼3.5 weeks (median). Many (40.6%) AEs leading to permanent discontinuation were grade 1/2, and most (87.2%) resolved or were resolving by 28 days after last treatment. Patients taking sunitinib showed a significantly lower EORTC QLQ-C30 overall health status score versus placebo, although this reduction was not clinically meaningful. Patients reported symptoms typically related to sunitinib treatment with diarrhea and loss of appetite showing clinically meaningful increases.Conclusions: In S-TRAC, AEs were predictable, manageable, and reversible via dose interruptions, dose reductions, and/or standard supportive medical therapy. Patients on sunitinib did report increased symptoms and reduced HRQoL, but these changes were generally not clinically meaningful, apart from appetite loss and diarrhea, and were expected in the context of known sunitinib effects.Clinical trial registration: ClinicalTrials.gov, NCT00375674.

Background Palbociclib, a selective inhibitor of CDK-4/6, prevents DNA synthesis by blocking cell cycle progression. A randomized Phase 2 study of palbociclib (P) 125 mg QD for 3 weeks followed by 1 week off plus letrozole (L) 2.5 mg QD continuously compared to L alone was conducted. A secondary objective of the study was to assess the impact of adding P in combination with L compared to L alone on pain severity and pain interference with various activities of daily life. Methods This Phase 2 trial was designed to evaluate P+L in front-line ER+/HER2- metastatic breast cancer (MBC) compared to L alone. The primary endpoint was investigator assessed progression-free survival (PFS) defined as time from randomization to objective progression or death. Patient reported outcomes of pain severity (PS) and pain interference (PI) with various activities of daily life were assessed using the Brief Pain Inventory (BPI) at baseline and day 1 of each cycle thereafter. The PS and PI scores were summarized by cycle using observed values as well as changes from baseline. Results The final analysis of primary endpoint showed a statistically significant improvement in PFS for the P+L arm (20.2 months) vs. L arm (10.2 months) with hazard ratio (HR)=0.488 (95% CI: 0.319, 0.748) and 1-sided p=0.0004. The most common adverse events in the P+L arm were neutropenia, leukopenia, fatigue, and anemia. For the PS scale, patients in the P+L arm showed numerically lower scores and greater reductions from baseline than the L arm, until the later cycles, when the number of patients had decreased to a small number. The difference between treatment arms in the mean change from baseline was statistically significant at some of the earlier cycles (Cycles 5, 6, 7, 8, 10, 12; p For the PI score, observed mean scores for both treatment arms appeared to be stable over time until the later cycles, when the number of patients had decreased to a small number. Patients in the P+L treatment arm also generally showed a consistently greater numeric reduction from baseline in pain interference (ie, a decrease in PI on daily activities) until later cycles although without reaching statistical significance at any cycle. Conclusions The addition of palbociclib to letrozole was associated with increased efficacy without negatively impacting pain severity or pain interference on daily activities. Citation Format: Timothy Bell, John Paul Crown, Istvan Lang, Helen Bhattacharyya, Giovanni Zanotti, Sophia Randolph, Sindy Kim, Xin Huang, Cynthia Huang Bartlett, Richard Finn, Dennis Slamon. Impact of adding palbociclib to letrozole on pain severity and pain interference with various activities of daily life in patients with ER+, HER2- metastatic breast cancer as first line treatment [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-19.

BACKGROUND: NCCN guidelines clearly identify when chemotherapy may be an appropriate therapeutic approach for metastatic breast cancer (mBC). This study compared patient characteristics, mortality rates, and health care costs by initial chemotherapy (CT) use among women with HR+/HER2- mBC. METHODS: A retrospective cohort study design was used to analyze administrative claims data linked to clinical information for commercial health plan enrollees with evidence of mBC between 1/2008 and 4/2013. Clinical status at diagnosis was obtained from physician reports, including date of diagnosis, hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Women with known HR+/HER2- subtype and diagnosed initially with Stage IV or Stages I-III with evidence of progression later to metastatic disease were evaluated for at least 6 months after their Stage IV diagnosis or first metastatic claim, or until death if sooner. Clinical characteristics were compared descriptively between women who initiated therapy with/without chemotherapy (CT 1st vs. no CT 1st, respectively) using t-test for continuous and chi-square test for categorical variables. Mortality was compared using the incidence rate ratio (IRR) and 95% confidence interval (CI) from a negative binomial distribution. Total average per-member-per-month (PMPM) health care costs were compared using a generalized linear model. Both the mortality rates and costs were adjusted for age, geographic region, stage at diagnosis, initial metastatic site(s), and initial use of CT. RESULTS: Of 349 women with HR+/HER2- mBC, 204 (58%) had CT 1st and 145 (42%) had no CT 1st. Median follow-up was 17 months, and median length of the first-line of therapy (1st LOT) was 4 months (including censored LOTs). The mean age of women with CT 1st was slightly lower than those without CT 1st (52 vs. 55 years, p CONCLUSION: In this study of commercially insured women with HR+/HER2- mBC, use of CT 1st (>50%) was higher than expected. While there were minor cohort differences in patient characteristics, CT 1st does not appear to be associated with a survival benefit, but was associated with significantly higher costs when compared to no CT 1st. Additional research is needed to determine subset(s) of mBC women with CT 1st likely to benefit from initial HT. Citation Format: Tanya Burton, Stacey DaCosta Byfield, Ying Fan, Yiyu Fang, Feng Cao, Gregory L Smith, Giovanni Zanotti, Timothy J Bell, Julia J Perkins, Ruslan Horblyuk, April Teitlebaum. 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 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-23.

BACKGROUND: Breast cancer is the second most common cause of cancer death among US women. Molecular profiling of breast cancer tumors is important for assessing prognosis and optimizing treatment. This study compared clinical characteristics and treatment utilization by tumor subtype among women with metastatic breast cancer (mBC). METHODS: A retrospective cohort study design was used to analyze administrative claims data linked to clinical information for commercial health plan enrollees with evidence of mBC between 1/2008 and 4/2013. Clinical status at diagnosis was obtained from physician reports, including date of diagnosis, hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Women with known HR/HER2 subtypes and diagnosed initially with Stage IV or Stages I-III with evidence of progression later to metastatic disease were evaluated for at least 6 months after their Stage IV diagnosis or first metastatic claim, or until death if sooner. Lines of therapy (LOTs) were identified based on the timing of claims for NCCN-recommended chemotherapy (CT), hormonal therapy (HT), and biologics (BIO). Clinical characteristics and treatments were compared descriptively across the HR/HER2 subtypes using t-test for continuous and chi-square test for categorical variables. RESULTS: Table 1 presents study results by tumor subtype. There were 657 women identified (72% HR+ and 28% HR-). Median age was 53 years, and median follow-up was 16 months. Overall, 93% initiated therapy; of which, 48% started a 2nd LOT, 4% died, 28% discontinued or had a ≥90-day gap in therapy, and 20% had their 1st LOT censored due to disenrollment or end of study (EOS) period. More than half received CT during the 1st LOT, regardless of tumor subtype. Less than half of HR+ women initiated HT, and among HER2+ patients, most initiated a BIO agent. Total (N=657)HR+/HER2- (N=365)HR-/HER2- (N=118)HR+/HER2+ (N=111)HR-/HER2+ (N=63)n(%)n(%)n(%)n(%)n(%)Diagnosed at Stage IV*265(40)145(40)37(31)50(45)33(52)Initial site of metastasis- Bone283(43)167(46)49(42)46(41)21(33)- Brain*105(16)45(12)32(27)17(15)11(17)- Liver*171(26)76(21)40(34)35(32)20(32)- Lung*127(19)64(18)36(31)11(10)16(25)- Other (incl. distant lymph nodes)494(75)277(76)97(82)76(68)44(70)Initial NCCN-recommended therapy (1st LOT)614(93)349(96)98(83)109(98)58(92)- CT*422(69)204(58)92(94)78(72)48(83)- BIO*124(20)1( CONCLUSION: In this study of commercially insured mBC women, initial therapy choices were generally consistent with NCCN guidelines for three of the four subtypes, while the largest subtype of HR+/HER2- women had a higher than expected utilization of CT. Future analyses of study data will investigate appropriateness of these initial treatments and their impact on clinical and economic outcomes. Citation Format: Tanya Burton, Stacey DaCosta Byfield, Ying Fan, Yiyu Fang, Feng Cao, Gregory L Smith, Giovanni Zanotti, Timothy J Bell, Julia J Perkins, Ruslan Horblyuk, April Teitlebaum. Clinical characteristics and treatment utilization by tumor subtype among metastatic breast cancer patients in a large US managed care health plan [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-24.

636 Background: It is unclear whether post-nephrectomy patients with renal cell carcinoma (RCC) in real-world practice settings are typically assessed for recurrence risk post-operatively and whether patients at high risk of recurrence are seen by providers who can evaluate candidacy for adjuvant systemic therapy (AST), clinical trials, or alternative surveillance schedules. Methods: We identified all patients with locoregional RCC who underwent nephrectomy within Duke University Health System between April 1, 2015 and March 31, 2019 via an institutional database. Medical records were reviewed to identify patient characteristics, post-nephrectomy treatment and referrals, and follow up. Patients with tumor stage 3 or higher and tumor grade 2 or higher, regional lymph-node metastasis, or both, were classified as high risk of recurrence. Results: Of 500 patients with locoregional RCC who underwent nephrectomy, 111 (22.2%) had high risk of recurrence (Table). 15 patients with high risk disease (13.5%) were referred to a medical oncologist for discussion of AST. Fourteen of the 15 referrals took place in 2018 or later. 7 of 29 (24.1%) high risk patients were referred for discussion of AST in 2018 and 7 of 9 (77.8%) in 2019. All referrals were made by urologists to medical oncologists. Two patients received AST – one as part of a clinical trial and one node-positive patient received standard-of-care sunitinib. In the cohort of high-risk patients, follow up data was available for 83 patients with median follow up time of 1.16 years; 31 patients (37.4%) developed recurrent disease. Conclusions: Within a single large academic institution, despite increasing numbers of patients with locoregional RCC at high risk of recurrence being referred to medical oncologists after nephrectomy, few patients received AST. These findings highlight the need for continued efforts at identifying effective AST and referring patients most likely to benefit.[Table: see text]

643 Background: In 2019, there was an estimated 73,820 new cases of kidney cancers in the US. The tx landscape for aRCC is changing rapidly. Recently approved txs for 1L aRCC include new targeted agents and immuno-oncology (IO) therapies. We examine outcomes for pts who completed 1L tx. Methods: Real-world data were drawn from the RCC Disease Specific Programme; a cross-sectional survey administered to US oncologists, nephrologists and urologists. Physicians completed pt record forms (PRFs) for up to the next 8 consulting aRCC pts receiving drug tx, from February - September 2019, plus additional optional PRFs for pts receiving/who had received either 1L tx of nivolumab/ipilimumab combination or cabozantinib, where these pts were available. Results: Physicians (n=82) provided data on 687 pts; 230 had progressed from 1L tx and were on 2L tx at time of data collection. Of those receiving 2L tx, 61% male; mean age was 66.4 years (SD=11.0); 43% stage IV at diagnosis. At 1L, 72% (n=165) had received tyrosine kinase inhibitor (TKI) monotherapy; 16% (n=37) IO+IO, 3% (n=7) TKI+IO and 9% (n=20) other regimens. Mean 1L duration was 10.3 months (SD=9.4) and mean time to 2L initiation was 13.7 months (SD=21.1). 1L treatment responses were: 6% complete response, 21% partial response, 16% stable disease, and the remainder relapsed/progressed (44%) or unknown response (13%). Most common 2L regimens were TKI (37%) or IO (34%) monotherapy. 47% of 1L TKI monotherapy pts received 2L IO monotherapy. 86% of 1L IO+IO pts received 2L TKI monotherapy. Conclusions: Some pts with aRCC progress to 2L; many experience poor clinical outcomes with 1L txs, highlighting high unmet need in 1L for more efficacious txs. Optimal tx strategy (and sequencing) continues to evolve. Approval of IO+TKI therapies, approved during the fieldwork period, has broadened the therapeutic landscape for 1L aRCC. Whilst the proportion of 1L pts receiving IO+TKI therapies is still low, the adoption of these in 1L is likely to transform the management of aRCC. Further research is needed to determine the optimum tx sequence in these pts with high unmet need.

Background Personalised tx is key in aRCC. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model determines prognosis of aRCC patients treated with systemic tx, helping guide treatment choice. This study examined real-world tx patterns and outcomes of 1L aRCC patients with differing IMDC status in the US. Methods Real-world data were drawn from the RCC Disease Specific ProgrammeTM; a cross-sectional study administered to oncologists, nephrologists and urologists in the US. Physicians completed patient record forms (PRFs) for up to the next 8 consulting RCC patients receiving active drug tx, from February - September 2019, plus additional optional PRFs for patients receiving/who had received either 1L nivolumab/ipilimumab combination tx or cabozantinib tx, where these patients were available. Study variables included patient demographics, background clinical information and tx patterns. Results Physicians (n = 82) provided data on 687 patients. 445 patients were receiving 1L tx at time of data abstraction. Of those receiving 1L tx, mean age was 64.2 years, and 69% of patients were male. 34% (n = 151) did not have a physician-assessed IMDC prognostic risk score, and 5% (n = 23) reported unknown. Of the 61% (n = 271) that had a physician-assessed IMDC prognostic risk score, 15% had a low risk, 63% had an intermediate risk and 21% had a high risk. In the intermediate and high risk group, tyrosine kinase inhibitor (TKI) monotherapy was the most common 1L therapy (45%, n = 103), followed by IO-IO combination (29%, n = 66). Conclusion ASCO and NCCN guidelines recommend IO-IO combination in patients with an intermediate or high IMDC risk. However, at the time of data collection, more patients meeting these criteria received TKI monotherapy than IO-IO combination; moreover, almost a third of 1L tx aRCC patients were not even assessed. Newly introduced IO-TKI combination tx, approved during the fieldwork period, could enable clinicians to offer patients personalised tx, irrespective of risk profile. Legal entity responsible for the study Pfizer Inc. Funding Pfizer Inc. (part of an alliance between Pfizer Inc. and Merck KGaA, Darmstadt, Germany). Disclosure G. Zanotti: Shareholder / Stockholder / Stock options: Pfizer; Full / Part-time employment: Pfizer. R. Kim: Full / Part-time employment: Pfizer; Shareholder / Stockholder / Stock options: Exelixis. S.P. Krulewicz: Shareholder / Stockholder / Stock options: Pfizer; Full / Part-time employment: Pfizer. J.P. Hall: Full / Part-time employment: Adelphi Real World. A. Leith: Full / Part-time employment: Adelphi Real World. A. Bailey: Full / Part-time employment: Adelphi Real World. F. Liu: Full / Part-time employment: EMD Serono, Inc. M. Kearney: Full / Part-time employment: Merck KGaA, Darmstadt, Germany; Shareholder / Stockholder / Stock options: Novartis Pharma; Shareholder / Stockholder / Stock options: UCB Pharma; Shareholder / Stockholder / Stock options: SPRL.