Results Of Pivotal Trials Research Articles

8654 Real-World Performance Of The Medtronic Extended Infusion Set In The United States

Abstract Disclosure: T. Kwa: Employee; Self; Medtronic Minimed. G. Zhang: Employee; Self; Medtronic Minimed. J. Kiehl: Employee; Self; Medtronic Minimed. V. Putcha: Employee; Self; Medtronic Minimed. A. Patel: Employee; Self; Medtronic Minimed. S. Chattaraj: Employee; Self; Medtronic Minimed. O. Cohen: Employee; Self; Medtronic Minimed. R.A. Vigersky: Employee; Self; Medtronic Minimed. Real-World Performance of the Medtronic Extended Infusion Set in the United States Objective: The Medtronic extended infusion set (EIS) is the first and only infusion set approved for up to 7-day use and its pivotal trial established clinical safety and efficacy.[1] The purpose of this retrospective analysis was to assess real-world EIS performance and overall glycemic outcomes based on United States (US) data uploaded by MiniMed™ 770G system (MM770G) users at an aggregate level. Methods: Infusion set occlusion alarm events and time in (TIR, 70-180 mg/dL), below (TBR, <70 mg/dL) and above (TAR, >180 mg/dL) range of EIS-MM770G users (N=393) with >30-day device use in the U.S. were analyzed and compared against the data of a cohort of the same median age of 50 years (N=77219) using the MM770G with a standard 2/3-day infusion set (at an aggregate level). Results: EIS users experienced a lower occlusion alarm rate (median 0.011 alerts/patient day) compared to 0.016 alerts/patient day with the standard set (p = 0.005). TIR for EIS users was 69.4%, which was numerically greater than the 69.1% for standard set users (p = 0.258). While TAR was not significantly different (28.9% for EIS and 29.0% for standard set, p = 0.995), TBR was significantly lower (0.5% for EIS and 1.3% for standard set, p = 0.000). The difference in the total daily dose (TDD) of insulin between the two groups (53.0 units for EIS, 49.4 units for standard set) was not statistically significant (p = 0.961). Conclusion: Since the U.S. launch, the EIS has continued to perform similarly to the pivotal trial results and an early real-world analysis of EIS use outside of the US.2 The decreased burden of fewer set changes comes with a lower occlusion alarm rate and does not compromise time spent in target range.

Safety, efficacy, and reliability evaluation ofa novel small-diameter defibrillation lead: Global LEADR pivotal trial results

BackgroundImplantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure defibrillation lead is a novel, small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform. ObjectiveThis trial assessed safety and efficacy of the OmniaSecure defibrillation lead. MethodsThe worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead–related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively. ResultsIn total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead–related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD). ConclusionThe OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures.

Review of Current Treatment Intensification Strategies for Prostate Cancer Patients

Prostate cancer (PCa) used to be one of the most common nondermatologic cancers in men that can be treated only with surgery. However, a revolutionary breakthrough came in the 1980s with the introduction of long-acting luteinizing hormone-releasing hormone (LHRH) agonists for the curative treatment of PCa. This paradigm shift contributed to the combined use of androgen deprivation therapy (ADT), chemotherapy, and radiotherapy for the treatment. The latest data highlight the use of treatment intensification (TI), i.e., combined use of radiotherapy (RT) and hormonal or drug treatments, for localized or locally advanced PCa. Indeed, the results of combined modality treatments have shown a reduction in disease-specific mortality and improved overall survival. Although TI seems promising, more research studies are warranted to confirm its efficacy. This review summarizes the latest available outcome results of pivotal trials and clinical studies on the efficacy of TI.

910-P: Real-World Clinical Data on the Extended Infusion Set

Objective: The Medtronic Extended infusion set (EIS) is the first and only infusion set approved for up to 7-day use. Prior studies established clinical safety and efficacy of the EIS. The purpose of this retrospective analysis was to assess real-world data on the EIS performance and user behaviors associated with the EIS including wear duration and asynchronous reservoir changes. Methods: A limited launch of the EIS outside the US (OUS) included MiniMed™ 640G/670G/780G users. Due to regional legal requirements, aggregated pump data from EIS users were not separated from other user data. To identify EIS users, an algorithm was developed based on the expected behavior patterns associated with an infusion set change, e.g., tubing fills. From the same cohort, individuals using the EIS (n=108) versus regular 3-day sets (n=414) were identified by a mean or median time between substantial tubing fills. To assess synchronous and asynchronous set/reservoir changes, reservoir changes were determined based on pump rewind commands in the CareLink™ system. Results: Mean EIS use lifetime was 6.74 days, with >70% of sets used for more than 6 days. No user complaint was received during limited launch. The EIS set change rate at 7 days (168 hrs) was 48.2%, and was comparable to the 48.9% rate of 3-day sets at 3 days (72 hrs). In addition, CareLink™ data indicated that while users with a total daily dose (TDD) of insulin less than 40 U may not require an asynchronous reservoir fill, some users with higher TDD did asynchronously and successfully change their reservoirs while retaining the infusion set. Conclusion: In the OUS limited EIS launch, the EIS performed similarly to the pivotal trial results, with no user complaints. As expected, pump users with TDD less than 40 U changed the infusion set and reservoir at the same time on the seventh day. The product has launched in the US and may potentially reduce user burden by effectively halving the number of required infusion set changes compared to standard 3-day sets. Disclosure T.Kwa: Employee; Medtronic. G.Zhang: Employee; Medtronic. A.Roy: Employee; Medtronic. M.Liu: Employee; Medtronic. E.Anselmo: Employee; Medtronic. J.Shin: Employee; Medtronic. O.Cohen: Employee; Medtronic. S.Chattaraj: Employee; Medtronic.

WED-330 - The effects of alfapump on ascites control and quality of life in patients with cirrhosis and recurrent or refractory ascites: pivotal trial results

WED-330 - The effects of alfapump on ascites control and quality of life in patients with cirrhosis and recurrent or refractory ascites: pivotal trial results

Multifidus Stimulation in Patients with Refractory Chronic Low Back Pain and Functional Spine Instability – Three-Year Pivotal Trial Results

Multifidus Stimulation in Patients with Refractory Chronic Low Back Pain and Functional Spine Instability – Three-Year Pivotal Trial Results

ID:16274 Three-Year Durability of Restorative Neurostimulation for Mechanical Chronic Low Back Pain: Pivotal Trial Results

Mechanical chronic low back pain (CLBP) can be caused by impaired neuromuscular control and degeneration of the multifidus muscles, the most important stabilizers of the lumbar spine. An implantable Restorative Neurostimulation system (ReActiv8® by Mainstay Medical) bilaterally stimulates the medial branches of the L2 dorsal rami to override underlying multifidus inhibition to facilitate motor control restoration. The ReActiv8-B randomized sham-controlled pivotal trial provided evidence of safety, effectiveness and durability of this therapy (clinicaltrials.gov/show/NCT02577354).[1,2] Here we report the three-year durability results.

Cancer Therapy Approval Timings, Review Speed, and Publication of Pivotal Registration Trials in the US and Europe, 2010-2019

Ensuring patients have access to safe and efficacious medicines in a timely manner is an essential goal for regulatory agencies, one which has particular importance in oncology because of the substantial unmet need for new therapies. The 2 largest regulatory agencies, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have pivotal global roles, and their recommendations and approvals are frequently followed by other national regulators. To compare market authorization dates for new oncology therapies approved in the US and Europe over the past decade and to examine and contrast the regulatory activities of the FDA and EMA in the approval of new cancer medicines. This cross-sectional study reviewed the FDA and EMA regulatory databases to identify new oncology therapies approved in both the US and Europe from 2010 to 2019, and characterization of the timings of regulatory activities. Statistical analysis was performed from January to April 2022. Regulatory approval date, review time, submission of market authorization application, accelerated approval or conditional marketing authorization status and proportion of approvals prior to peer-reviewed publication of pivotal trial results. In total, 89 new concomitant oncology therapies were approved in the US and Europe from 2010 to 2019. The FDA approved 85 oncology therapies (95%) before European authorization and 4 therapies (5%) after. The median (IQR) delay in market authorization for new oncology therapies in Europe was 241 (150-370) days compared with the US. The median (IQR) review time was 200 (155-277) days for the FDA and 426 (358-480) days for the EMA. Sixty-four new licensing applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA. Thirty-five oncology therapies (39%) were approved by the FDA prior to pivotal study publication, whereas only 8 (9%) by the EMA. In this cross-sectional study, new oncology therapies were approved earlier in the US than Europe. The FDA received licensing applications sooner and had shorter review times. However, more therapies were approved prior to licensing study publication, leaving uncertainty for practitioners regarding clinical utility and safety of newly approved therapies.

Rapid adoption of immunotherapy in community health systems, associated with changing treatment guidelines.

e18610 Background: In the quickly evolving landscape of developmental therapeutics, uptake of new standards of care is a critical issue. Community health systems (CHS) provide > 50% of cancer care in the US. Rapidly changing immunotherapy (IO) guidelines provide a window into changing practice patterns. This analysis describes how IO use has evolved within CHS. Methods: Patients (pts) selected were ≥ 18 years, diagnosed with advanced or metastatic NSCLC 2015-2020, with 2+ EHR encounters before 4/1/2021. Two sub cohorts were analyzed. Cohort 1: pts receiving IO in any line of therapy (L); first use of IO by L was assessed over time. Cohort 2: pts receiving any first L (1L) therapy; 1L use of IO, alone or with chemotherapy (IO combo), was assessed over time. Results: In cohort 1, IO use in 1L grew from 24% of all IO pts in 2016 to 93% in 2020, increasing from 33% in Q4 2016 to 62% in Q1 2017. In cohort 2, 1L therapy shifted from 4% of all pts receiving IO in 1L in 2016 to 59% in 2020, increasing from 6% in Q4 2016 to 24% in Q1 2017. Within IO 1L pts, IO combo use grew from 29% to 68% in 2020, increasing from 35% in Q1 2018 to 53% in Q2 2018. Conclusions: We observed two rapid shifts in care patterns. First, 1L IO use grew rapidly from Q4 2016 to Q1 2017, following 1L IO approval (10/2016). Second, 1L IO use shifted rapidly toward IO combo use from Q1 2018 to Q2 2018, coinciding with pivotal trial results and FDA priority review (4/2018), but preceding label expansion (8/2018). Two RWD analyses from independent oncology practices observed less substantial shifts during similar periods of time. These results demonstrate that CHS can rapidly adjust to evolving clinical evidence and associated changes in standards of care.[Table: see text]

Systemic treatment of recurrent and/or metastatic squamous cell carcinomas of the head and neck: what is the best therapeutic sequence?

The treatment of recurrent and/or metastatic head and neck squamous cell carcinoma patients is revolutionized by the advent of anti-PD1 checkpoint inhibitors. Indeed, Pembrolizumab is approved as monotherapy or used in combination with platin and fluorouracil for first-line patients with tumors expressing PD-L1. Nivolumab and Pembrolizumab are also approved in second line of recurrent/metastatic head and neck squamous cell carcinoma. Moreover, the substitution of fluorouracil for a taxane in the TPEx regimen has shown improvement in safety profile when compared with EXTREME regimen. Here we carry out a review of the main results of pivotal trials and discuss the pros and cons of the three possible scenarios when considering the therapeutic sequence (first and second line).

Prevalence of SGLT2i and GLP1RA use among US adults with type 2 diabetes

AimsTo determine national prevalence of sodium-glucose contransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP1RA) use among adults with type 2 diabetes mellitus (T2DM). MethodsWe studied adults with T2DM and eGFR ≥ 30 mL/min/1.73 m2 who participated in the cross-sectional National Health and Nutrition Examination Survey (NHANES), focusing on the 2017–2020 examination cycle, a key time period prior to widespread dissemination of pivotal trial results and corresponding clinical practice guidelines. We tested prevalence of SGLT2i and GLP1RA use among subgroups based on demographic variables and relevant comorbidities, including chronic kidney disease (CKD), congestive heart failure (CHF), and atherosclerotic cardiovascular disease (ASCVD). We compared use of SGLT2i and GLP1RA to other glucose-lowering medications and assessed trends from prior NHANES cycles. ResultsAmong 1375 participants studied in 2017–2020, mean age was 60 years, 46% were women, 13% self-identified as non-Hispanic Black, 10% self-identified as Mexican American, 37% had CKD, 8.5% had CHF, and 23% had ASCVD. The prevalence of SGLT2i and GLP1RA use was 5.8% and 4.4%, respectively. Among adults with CKD, CHF, or ASCVD, SGLT2i were used by 7.7% and GLP1RA were used by 3.5%. Differences in SGLT2i or GLP1RA use were observed by age, race, ethnicity, health insurance status, body mass index, and by whether a single healthcare provider was identified as responsible for diabetes management. Biguanides, sulfonylureas, DPP-4 inhibitors, and insulin were used more frequently than SGLT2i or GLP1RA. Prevalence of SGLT2i but not GLP1RA use increased significantly from 2013–2014 to 2017–2020. ConclusionsSGLT2i and GLP1RA use is low among adults with T2DM, including among those with strong indications. Enhanced implementation of these agents is crucial to improving kidney and cardiovascular outcomes and mitigating health disparities in T2DM.

PNH in the Pandemic: New Science and New Treatments in the Spotlight at ASH 2021

The 63rd ASH Annual Meeting featured a solid scientific line-up on paroxysmal nocturnal hemoglobinuria (PNH), despite the rarity of the disease, with five events and 23 posters. For Canadian PNH specialists, the key data surrounded C5-inhibitor ravulizumab, the second therapy available in Canada for PNH after an 8-year gap which made its appearance during the COVID-19 pandemic. Also at the meeting were reality checks on pivotal-trial results through the power of registry and EMR data, correlations between clinical parameters and patient quality-of-life (QoL) and timely clinical guidance on SARS-CoV-2 vaccination in PNH patients.

Long-Term Durability of Restorative Neurostimulation for Chronic Mechanical Low Back Pain – Two-Year Pivotal Trial Results

Introduction: Chronic mechanical low back pain (CMLBP) can be caused by impaired neuromuscular control and degeneration of the multifidus muscles resulting in functional instability of the lumbar spine. Available treatment options often lack long-term effectiveness and prognosis is unfavourable. An implantable Restorative Neurostimulation system (ReActiv8® by Mainstay Medical), that stimulates the L2 medial branches of the dorsal rami to reactivate neuromuscular control, received FDA Premarket Approval based on evidence from the ReActiv8-B pivotal trial (clinicaltrials.gov/show/NCT02577354).

Demographic characteristics of the 1902 transthyretin amyloid cardiomyopathy patients treated by tafamidis through the French early access program

Abstract Background Transthyretin amyloidosis (ATTR) is a rare and serious, systemic disease characterized by deposits of amyloid fibrils in various tissues and organs. Tafamidis meglumine is a potent and selective stabilizer of TTR, indicated since 2011 in the treatment of neurological forms of the disease. The French “Agence Nationale de Sécurité du Médicament et des produits de santé” (ANSM) granted a temporary recommendation for use (RTU) on November 28th 2018, based on ATTR-ACT, the pivotal trial results, and designed to enable use of tafamidis meglumine in ATTR cardiomyopathy (ATTR-CM) patients with NYHA I, II and III before marketing authorization. This RTU has been a unique opportunity in France to collect real world data of ATTR-CM patients treated by tafamidis meglumine. Objective We aimed to describe the characteristics of ATTR-CM patient treated by tafamidis in the setting of the RTU, over 2 years from November 28th 2018 to November 27th 2020. Methods Demographic and clinical data about the diagnosis pathway of patients included in the RTU were prospectively collected using questionnaires, as requested by ANSM to be completed by physicians at the time of tafamidis prescription. A second version of the inclusion form, introduced in May 2020, has allowed collection of additional clinical information. Results Overall, 1902 ATTR-CM patients have been included by 189 physicians from 107 centers. Nine centers included each at least 50 patients, accounting for 1092, or 57.4% of all patients. The median age of the patients was 82 years (IQR=9 years), 82% were male, and, 12.4%, 58.8% and 28.7% of patients had a NYHA class of I, II and III, respectively. For almost all patients, the diagnosis of restrictive/infiltrative heart failure was based on heart MRI and/or echocardiography (98.5%; among the 601 patients included from May 2020 28.8% had both exams, 69.7% echo only and 1.6% MRI only), the infiltrative nature of the cardiomyopathy had been confirmed by bone scintigraphy (99.3%), and the absence of light chains had been confirmed by protein electrophoresis or Bence Jones proteinuria (96.6%). Genetic test was performed in 1205 patients (69.4%). Out of the 884 patients who had a genetic test result available at the time of initial prescription, 762 (86.2%) were affected with the wild-type form and 122 (13.8%) with the hereditary form. Among the 601 patients included from May 2020, a hospitalization for cardiovascular condition within the 6 months preceding tafamidis initiation was reported for 22.3% of them, and tafamidis was initiated within 12 months after diagnosis for 92% of them (only 8% initiated the treatment beyond that period). Conclusion The RTU program has provided 1902 ATTR-CM patients with early access to tafamidis over 24 months, in France. Overall, as compared to patients included in ATTR-ACT, the pivotal trial, RTU patients were older, the proportion of wild-type was slightly higher, and NYHA distributions were similar. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Early access program sponsored by Pfizer

304P Incidence and resolution of eribulin-induced peripheral neuropathy (IRENE) in patients with locally advanced or metastatic breast cancer

Eribulin (ERI), a halichondrin-class microtubule dynamics inhibitor, is a typical chemotherapeutic regimen for patients (pts) with previously treated locally advanced or metastatic breast cancer (MBC). Results of pivotal trials showed that about one-third of pts with locally advanced or MBC treated with ERI develop peripheral neuropathy (PN), a common risk with BC chemotherapies. This postauthorization safety study assessed the incidence and severity of ERI-induced PN (EIPN) in pts with locally advanced or MBC.

Real-world assessment of response to anti-programmed cell death 1 therapy in advanced cutaneous squamous cell carcinoma

Real-world assessment of response to anti-programmed cell death 1 therapy in advanced cutaneous squamous cell carcinoma

P1376IRON MANAGEMENT IN A HAEMODIALYSIS POPULATION POST-PIVOTAL

Abstract Background and Aims IV iron plays a critical role in the management of anaemia in haemodialysis patients. The PIVOTAL trial recently generated new insights in this context, and suggested potential harm associated with under-treatment with IV iron. To perform a prospective cross-sectional survey of iron management in a single-centre haemodialysis population in light of the results from the PIVOTAL trial. Method During June 2019, we prospectively measured haemoglobin, serum ferritin and transferrin saturation in a prevalent haemodialysis population at a tertiary renal centre. The current dose of IV iron sucrose was also recorded. Extrapolating from the PIVOTAL trial results (best outcomes in the high-dose group with a mean ferritin of around 650 ng/ml and a TSAT of around 26%), we arbitrarily and conservatively defined under-treatment with iron as a ferritin level ≤500 ng/ml and a TSAT ≤25%. Results A total of 587 patients were identified, 581 of whom had a ferritin result available. Of these, 358 (62%) had a ferritin level ≤500 ng/ml and 295/527 (56%) had a TSAT ≤25%. For the 527 patients in whom both ferritin and TSAT measurements were available, 204/527 (39%) were defined as under-treated. Of the 587 patients, 111/582 (19%) were not receiving IV iron. 71/582 (12%) were on 100 mg monthly, 48/582 (8%) were on 200 mg monthly, 339/582 (58%) were prescribed 400 mg iron sucrose/month and 14/582 (2%) were on ≥ 400 mg. The iron dose was not available in 5 patients. Of the 204 undertreated population, 22 (11%) were not on IV iron. 17/204 (8%) were on 100 mg/month, 16/204 (8%) on 200 mg/month, 137/204 (61%) on 400 mg/month, and 11/204 (2%) on > 400 mg monthly. Of the patients defined as undertreated, the haemoglobin ranged from 63 to 151 g/l with a mean of 109.8 g/l and a median of 111 g/l. 30 patients had a haemoglobin less than 100 g/l and 92 patients had a haemoglobin less than 110 g/l. 24/204 patients were not on an ESA (one patient was on Daprodustat) with a mean dose of 12,200 U/week. Conclusion: Our current iron protocol is under-dosing a significant proportion of patients. This protocol requires review in light of the PIVOTAL study since it is likely significant cost savings could be achieved as a result of using lower doses of ESA therapy, along with the cardiovascular benefits seen in the higher dose arm of the trial.

PMU60 DO COMPANIES SEQUENCE THE LAUNCH OF INDICATIONS FOR MULTI-INDICATION PRODUCTS?

The majority of payors are unable to provide separate prices for different indications of a multi-indication product. Current pricing practices may create incentives for manufacturers to sequence the launch of different indications in order to avoid price erosion. This study examines the impact of pivotal trial design, pivotal trial results, and disease prevalence on the launch sequence of multi-indication products.

Neoadjuvant zoledronic acid for HER2-positive breast cancer: the Zo-NAnTax trial.

Background:Preclinical evidence suggests that zoledronic acid (ZOL) works synergistically with chemotherapy by enhancing anti-tumor activity. ZOL blocks the mevalonate pathway and may indirectly interact with human epidermal growth factor receptor 2 (HER2) pathway activation. The clinical efficacy and biological rationale of chemotherapy plus anti-HER2 therapy and ZOL as a part of neoadjuvant therapy has not been previously tested.Patients and methods:We conducted a phase II clinical trial to evaluate the efficacy and safety of ZOL as part of a neoadjuvant treatment in patients with HER2-positive breast cancer (BC). The protocol consisted of four cycles of doxorubicin/cyclophosphamide with ZOL, followed by four cycles of docetaxel with trastuzumab and ZOL prior to surgery. The primary endpoint was the pathologic complete response (pCR) rate. Secondary endpoints were safety and the identification of clinicopathological characteristics associated with pCR.Results:A total of 71 patients with stage IIA to IIIB BC were included, with 60 eligible for the safety assessment and 58 for the efficacy analysis. Overall, the pCR rate was 42%, with higher rates in hormone receptor (HR)-positive tumors (40%), which contrasts with the results of pivotal trials. The most commonly observed grade 3 and 4 events were febrile neutropenia (grade 3, 20%; grade 4, 3%) and diarrhea (grade 3, 12%).Conclusions:The addition of ZOL as a repositioning drug in neoadjuvant treatment was an effective and well-tolerated therapy. This drug combination might overcome endocrine and anti-HER2 resistance. The higher pCR rates in the HR-positive subgroup deserve further translational investigation.

Current and Emerging Treatments for Metastatic Renal Cell Carcinoma.

In the last decades, the treatment of mRCC, metastatic Renal Cell Carcinoma, has become more and more complex due to the approval of a great number of effective systemic treatments that have significantly improved the prognosis of patients suffering from such disease. An additional knowledge of the genetic aberrations and the molecular pathways alterations that underlie RCC, has promoted the development of several novel agents, known as target therapies (TTs). Even though TTs are not curative and all patients eventually progress, an adequate sequencing of these drugs can provide a significant benefit in terms of PFS, Progression Free Survival, and hopefully OS, Overall Survival. To date, there are few data about the optimal sequential use of the TTs hence, in clinical practice, the therapeutic strategy is chosen on the basis of the safety profile of the drug, patients medical history and the pivotal trial results, though such studies often exclude patients with poor performance status and/or severe comorbidities that we routinely see in our clinics. This review aims to provide an overview of the systemic therapies for mRCC both in the newly diagnosed patients and in the subsequent lines of treatment, with a special focus on the last advances about TTs and immunotherapy.