Systemic therapy in genitourinary cancers Souvenirs from the 34th Annual EAU Congress in Barcelona Prof. Maria De Santis Charité University Hospital Dept. of Urologic Oncology Berlin (DE) maria.de-santis@ charite.de
Professor Shore concluded that: • requirements for effective immunotherapy include adequate number of immune cells that can recognise and kill tumour cells; • we should allow those cells to be functional in a tumour micro-environment; • one way to generate tumour specific immune cells is a vaccine, but vaccine alone is not likely to be sufficient to cause an overall response rate in mCRPC; • immune checkpoint inhibition is unlikely to provide measurable response in mCRPC; • combination approaches are necessary to provide the best opportunity for clinically relevant activity.
Systemic therapy in genitourinary (GU) cancers is rapidly evolving. Nearly all GU tumours are suitable for treatment. The immune system is in the focus of many researchers and has widened our understanding of cancer development. Immunotherapy (IO) has added With regard to clear cell renal cell cancer (ccRCC), the to the current treatment paradigm, in particular for souvenir session provided a summary, particularly renal cell and urothelial cancer. pointing out that immunotherapy has entered the first-line setting for metastatic ccRCC. The guidelines In Thematic Session 1, Prof. Laurence Albiges (FR) have already been adapted and followed the summarised the exciting research on the human significantly positive results of the CheckMate 214 microbiome and in particular preclinical data on gut trial: the combination ipilimumab/nivolumab has microbes and how this can change our immune become the recommended treatment for intermediate response and response to treatment. Humans are and poor risk metastatic ccRCC. home to 39 trillions of microbes that process nutrients, produce vitamins and protect from new microbes. The But there is more to come: the combination of axitinib microbiome can shape the immune system and change plus pembrolizumab versus sunitinib was positive for the first endpoints progression free survival (PFS) and microbes in the host, which has shown to induce response to immunotherapy in mice. In summary, Prof. overall survival (OS) in all risk groups and independent of any biomarkers. The combination axitinib plus Albiges pointed out that there has been a paradigm avelumab provided first positive PFS data in biomarker shift in oncology, from tumour cells, to the immune selected programmed death-ligand 1 positive (PD-L1+) system and now to the host and its environment. patients (co-primary endpoint) compared to sunitinib. This includes hosted microbes and life style. The results of the co-primary endpoint OS in PD-L1+ patients are still pending. Professor Neal Shore (US) gave a lecture on immunotherapy for prostate cancer (PCA) and explained that its current role in prostate cancer is still In summary, for patients with metastatic ccRCC we do have a new standard of care with ilimumab/ limited and research is ongoing. He shared with the nivolumab for intermediate and poor risk patients. audience the experimental algorithm for Two TKI/IO combinations are awaited for unselected immunotherapy for metastatic castration-resistant patients in the first line setting (axitinib/ prostate cancer (mCRPC). This is based on the pembrolizumab in all patients and axitinib/avelumab approval of the PD-1 inhibitor pembrolizumab for all in PD-L1 positive patients). cancers that show microsatellite instability high (MSI-H) status1. Only 5% or less of PCA patients are MSI-H. Nonetheless, it is important to know that such patients show a significant response to the checkpoint inhibitor (CPI) pembrolizumab and also long-term benefit. In some institutions, this led to the testing of all mCRPC patients for MSI-H. The majority of PCA patients who are MSI-H negative should not receive monotherapy with CPI but should be included in IO combination trials. A plethora of such trials is ongoing including IO plus PARP inhibitors, IO plus radium 223, IO plus chemotherapy and IO plus hormonal combinations such as androgen deprivation therapy ©M De Santis, EAU 2019 Souvenir Session (ADT) and enzalutamide or abiraterone/prednisolone. Is early Immunotherapy better? [©N Shore, EAU 2019] Sipuleucel-T remains the only approved IO for PCA in the US. It improves overall survival (OS) but has limited impact on PSA or other clinical parameters. There is evidence that it is best given early in mCRPC. One interesting trial is the ProVent study that randomises Sipuleucel-T versus standard active surveillance in low risk/ISUP grade 1 or 2 patients who are eligible for active surveillance.
Moving IO therapy to an earlier phase in the treatment paradigm is in the focus of clinical research, also in RCC.
Expert guided poster tour In the expert guided poster tour, Prof. Bjartell discussed the concept of the ‘trial in progress’ poster, PT128 on CheckMate 914, a phase 3 randomised controlled trial (RCT), in which adjuvant nivolumab Another DNA-vaccine trial (see slide below) is aiming plus ipilimumab or placebo are under investigation in at an immune response and altering the biology of high risk RCC patients. early PCA. There were no significant safety findings The IO/IO combination is and most AEs were associated with injection site planned for 24 weeks. reactions. The interesting news is that there are This trial explores the significant clinical effects: concept of moving the • Evidence of dampening % rise in PSA and increased prostate specific antigen (PSA) doubling successful combination upfront, hoping to time (DT) in the majority of patients. improve survival and • A PSA stabilising effect of immunotherapy was cure. The trial started in noted in patients with no demonstrated disease progression or additional therapies by week 27. This July 2017 and the targeted stabilising effect continued into week 72. This effect number of patients is around 800 in 20 was noted in all patients, regardless of baseline countries. PSA-DT or patients with baseline DT < 6 months. • Further analysis is ongoing to elucidate correlation The current treatment of immunologic efficacy and clinical benefit. highlights for advanced and metastatic prostate cancer were mainly in the metastatic hormone sensitive (mHSPC) and the non-metastatic CRPC (M0CRPC) settings. In the latter, apalutamide and enzalutamide were recently approved for the treatment of M0CRPC. At this EAU meeting, data March/May 2019
on darolutamide were presented and discussed in the plenary session. Darolutamide is structurally distinct from apalutamide and enzalutamide. It shows low blood–brain barrier penetration and low potential for drug–drug interaction. Darolutamide is of special interest because these features could result in less central nervous system toxicity and improved tolerability. The summary of the ARAMIS trial, which compared darolutamide to placebo in men with M0CRPC and PSADT ≤ 10 months, was that the agent significantly improves metastasis-free survival (MFS, primary endpoint) in this patient group. The median MFS was 40.4 months with darolutamide versus 18.4 months with placebo. Also, darolutamide has a favourable safety profile which makes it an attractive option for treating nmCRPC2.
For mHSPC both docetaxel and abiraterone/ prednisolone showed to improve survival in phase 3 randomised controlled trials and meta-analyses. In the same patient population, ARCHES evaluated enzalutamide versus placebo and showed a significant radiographic progression-free survival benefit. The OS data is still immature and eagerly awaited.
In summary, at this year’s EAU annual meeting, exciting news on immunotherapy for GU cancers was presented and discussed. The programme also included sessions for mRCC and metastatic prostate cancer with regard to new data and treatment options which were put into clinical context for daily practice. References 1. Le DT, Uram JN, Wang H, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015;372:2509–20. 2. Fizazi K, Shore N, Tammela TL, et al. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med 2019;380:1235–46.
EAU19 section: EAU19: Once more raising the bar for urological meetings. . . . . . . . . . . . . . . . . . . . 1 Chapple starts second term . . . . . . . . . . . . . . 2 Systemic therapy in genitourinary cancers. . . 3 Three prostate imaging techniques highlighted. . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Overview of new developments in urothelial cancer . . . . . . . . . . . . . . . . . . . . . . 4 How Spain’s urology was shaped by its empire. . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 EAU19 update from the Guidelines Office. . . . 5 Overview of pizes and awards at the 34th Annual EAU Congress. . . . . . . . . . 6-9 EAU Patient Information Specialty Session at EAU19 . . . . . . . . . . . . . . . . . . . . . 10 EAU Patients Advocacy Group (EPAG). . . . . . 10 Key articles from international medical journals. . . . . . . . . . . . . . . . . . . . 11-14 Prague meeting to give complete LUTS update. . . . . . . . . . . . . . . . . . . . . . . . . 16 EULIS19 to present stone management essentials in Milan. . . . . . . . . . . . . . . . . . . . 16 ESU section: ESU unveils urolithiasis updates at Pan-Hellenic congress . . . . . . . . . . . . . . . . . 17 ESU offers UTI & ED fundamentals at RSU congress. . . . . . . . . . . . . . . . . . . . . . 17 Participants review NMIBC Masterclass. . . . . 18 FT masterclass presents disruptive technologies. . . . . . . . . . . . . . . . . . . . . . . . . 19 1st UROBESTT features fresh innovations and talent. . . . . . . . . . . . . . . . . 20 CAUREP unveils urology essentials in Punta Cana. . . . . . . . . . . . . . . . . . . . . . . . 22 Pre- and post-pubertal fertility preservation in males. . . . . . . . . . . . . . . . . . 23 ESUO: Treatment of simple urinary tract infections in Europe. . . . . . . . . . . . . . . 24 ESFFU: Tips & tricks to avoid complications, optimise management . . . . . 25 Clinical Challenge. . . . . . . . . . . . . . . . . . . . . 26 EAU RF launches PHOENIX registry. . . . . . . . 27 EBU: Berne Urological University Hospital EBU re-certified . . . . . . . . . . . . . . . 27 YUO section: Nightmare case: Rare gigantic emphysematous cystitis. . . . . . . . . . . . . . . . 28 The BURST Collaborative: Progress and news. . . . . . . . . . . . . . . . . . . . 29 USANZ Trainee Week . . . . . . . . . . . . . . . . . . 30 EULIS: Robotic flexible ureteroscopic stone management. . . . . . . . . . . . . . . . . . . . 30 EAU RF: BCG biomarker research profits from NIMBUS trial. . . . . . . . . . . . . . . 31 ESOU19 sums up vital onco-urology updates . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 ERUS19: New indications, new technology, new training . . . . . . . . . . . 33 European Tour 2019: Academic Exchange Programme with Taiwan and Japan . . . . . . . 34 European Tour 2019: Academic Exchange Programme with Canada . . . . . . . . . . . . . . . 36 EAUN section: Highlights and impressions of EAUN19 in Barcelona . . . . . . . . . . . . . . . . . . Animated narratives in a digital platform. . . 4th EAUN workshop at EUSC 2018 in Dubai. . . . . . . . . . . . . . . . . . . . . . . . . . . . Annual Conference 2018 of Society of Urologic Nurses. . . . . . . . . . . . . . . . . . . . Anniversary 20th EAUN Meeting in Barcelona. . . . . . . . . . . . . . . . . . . . . . . . .
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