Tag Archive for: Immunotherapy

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Article of the week: Patient‐reported outcomes in a phase 2 study comparing atezolizumab alone or with bevacizumab vs sunitinib in previously untreated metastatic renal cell carcinoma

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

If you only have time to read one article this week, we recommend this one. 

Patient‐reported outcomes in a phase 2 study comparing atezolizumab alone or with bevacizumab vs sunitinib in previously untreated metastatic renal cell carcinoma

Sumanta K. Pal*, David F. McDermott, Michael B. Atkins, Bernard Escudier§, Brian I. Rini, Robert J. Motzer**, Lawrence Fong††, Richard W. Joseph‡‡, Stephane Oudard§§, Alain Ravaud¶¶, Sergio Bracarda***, Cristina Suárez†††, Elaine T. Lam‡‡‡, Toni K. Choueiri§§§, Beiying Ding¶¶¶, Caroleen Quach¶¶¶, Kenji Hashimoto****, Christina Schiff¶¶¶, Elisabeth Piault-Louis¶¶¶ and Thomas Powles††††

*Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA, §Gustave Roussy, Villejuif, France, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, **Memorial Sloan Kettering Cancer Center, New York, NY, ††School of Medicine, University of California, San Francisco, San Francisco, CA, ‡‡Mayo Clinic Hospital, Jacksonville, FL, USA, §§Department of Medical Oncology, Georges Pompidou Hospital, Paris Descartes University, Paris, ¶¶CHU Hôpitaux de Bordeaux, Hôpital Saint-André, Bordeaux, France, ***Azienda Ospedaliera S. Maria, Terni, Italy, †††Vall d’Hebron University Hospital and Institute of Oncology, Barcelona, Spain, ‡‡‡Anschutz Medical Campus, University of Colorado, Aurora, CO, §§§Dana-Farber Cancer Institute, Boston, MA, ¶¶¶Genentech, Inc., South San Francisco, CA, USA,****Roche Products Ltd, Welwyn Garden City, and ††††Barts Cancer Institute, Royal Free Hospital, Queen Mary University of London, London, UK

Abstract

Objective

To evaluate patient‐reported outcome (PRO) data from the IMmotion150 study. The phase 2 IMmotion150 study showed improved progression‐free survival with atezolizumab plus bevacizumab vs sunitinib in patients with programmed death‐ligand 1 (PD‐L1)+ tumours and suggested activity of atezolizumab monotherapy in previously untreated metastatic renal cell carcinoma (mRCC).

Patients and methods

Patients with previously untreated mRCC were randomised to atezolizumab 1200 mg intravenously (i.v.) every 3 weeks (= 103), the atezolizumab regimen plus bevacizumab 15 mg/kg i.v. every 3 weeks (= 101), or sunitinib 50 mg orally daily (4 weeks on, 2 weeks off; = 101). The MD Anderson Symptom Inventory (MDASI) and Brief Fatigue Inventory (BFI) were administered on days 1 and 22 of each 6‐week cycle. Time to deterioration (TTD), change from baseline in MDASI core and RCC symptom severity, interference with daily life, and BFI fatigue severity and interference scores were reported for all comers. The TTD was the first ≥2‐point score increase over baseline. Absolute effect size ≥0.2 suggested a clinically important difference with checkpoint inhibitor therapy vs sunitinib.

Fig.3. Change in individual symptom severity during first‐line treatment based on MDASI. Atezo, atezolizumab; bev, bevacizumab; ES, effect size; MDASI, MD Anderson Symptom Inventory. aES ≤−0.20 favouring atezolizumab alone vs sunitinib. bES ≤−0.20 favouring atezolizumab plus bevacizumab vs sunitinib.

Results

Completion rates were >90% at baseline and ≥80% at most visits. Delayed TTD in core and RCC symptoms, symptom interference, fatigue, and fatigue‐related interference was observed with atezolizumab (both alone and in combination) vs sunitinib. Improved TTD (hazard ratio [HR], 95% confidence interval [CI]) was more pronounced with atezolizumab monotherapy: core symptoms, 0.39 (0.22–0.71); RCC symptoms, 0.22 (0.12–0.41); and symptom interference, 0.36 (0.22–0.58). Change from baseline by visit, evaluated by the MDASI, also showed a trend favouring atezolizumab monotherapy vs sunitinib. Small sample sizes may have limited the ability to draw definitive conclusions.

Conclusion

PROs suggested that atezolizumab alone or with bevacizumab maintained daily function compared with sunitinib. Notably, symptoms were least severe with atezolizumab alone vs sunitinib (IMmotion150; ClinicalTrials.gov Identifier: NCT01984242).

Article of the week: Update on the guideline of guidelines: non‐muscle‐invasive bladder cancer

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to this post, there is also a video produced by the authors. Please use the comment buttons below to join the conversation.

If you only have time to read one article this week, we recommend this one. 

Update on the guideline of guidelines: non‐muscle‐invasive bladder cancer

Jacob Taylor , Ezequiel Becher and Gary D. Steinberg

Department of Urology, NYU Langone Health, New York, NY, USA

Abstract

Non‐muscle‐invasive bladder cancer (NMIBC) is the most common form of bladder cancer, with frequent recurrences and risk of progression. Risk‐stratified treatment and surveillance protocols are often used to guide management. In 2017, BJUI reviewed guidelines on NMIBC from four major organizations: the American Urological Association/Society of Urological Oncology, the European Association of Urology, the National Comprehensive Cancer Network, and the National Institute for Health and Care Excellence. The present update will review major changes in the guidelines and broadly summarize new recommendations for treatment of NMIBC in an era of bacillus Calmette‐Guérin shortage and immense novel therapy development.

Video: Update on the guideline of guidelines: non‐muscle‐invasive bladder cancer

Update on the guideline of guidelines: non‐muscle‐invasive bladder cancer

Abstract

Non‐muscle‐invasive bladder cancer (NMIBC) is the most common form of bladder cancer, with frequent recurrences and risk of progression. Risk‐stratified treatment and surveillance protocols are often used to guide management. In 2017, BJUI reviewed guidelines on NMIBC from four major organizations: the American Urological Association/Society of Urological Oncology, the European Association of Urology, the National Comprehensive Cancer Network, and the National Institute for Health and Care Excellence. The present update will review major changes in the guidelines and broadly summarize new recommendations for treatment of NMIBC in an era of bacillus Calmette‐Guérin shortage and immense novel therapy development.

Residents’ Podcast: CUA 2018 review

Jesse Ory and Andrea Kokorovic
Department of Urology, Dalhousie University, Halifax, NS, Canada

Dalhousie residents Jesse Ory and Andrea Kokorovic sum up the highlights of day 1 at the 2018 Canadian Urological Association annual meeting in Halifax

Song credits
Don’t fear the reaper: Blue oyster cult
Mute city: F Zero
Mortal Kombat Theme: The Immortals
Funky Suspense – Bensound.com

BJUI Podcasts now available on iTunes, subscribe here https://itunes.apple.com/gb/podcast/bju-international/id1309570262

 

 

Highlights from the Urological Association of Asia Annual Congress 2017

Having trained and worked in London throughout my urology career, I have recently relocated and joined the exciting, dynamic urology community of my birthplace, Hong Kong. Coincidentally, it so happens to be this year’s host of the Urological Association of Asia (UAA) annual congress #UAA2017.

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The beautiful and mesmerising night view of the Victoria Harbour of Hong Kong.

Established in 1990 in Fukuoka, Japan, the #UAA currently has 25 urological associations as members or affiliated members across Asia and Australasia with and over 25,000 members. This was my attendance at the #UAA and it most certainly did not disappoint. What made the conference even more special was the chance to meet up with my good friend and ex-colleague from Guy’s Hospital @nairajesh – both of us were honoured to speak at the meeting. With over 1600 delegates attending the meeting and over 500 scientific abstracts presented, the congress served as an excellent platform for knowledge exchange and the establishment of professional links with many urological greats in Asia and beyond.

 

Pre #UAA2017 Congress Activities

#UAA2017 started off with a pre-congress ‘wet-lab’ 3D laparoscopic skills and endourology workshop hosted by @HKUniversity and the European School of Urology @UrowebESU. Both transperitoneal laparoscopic and retroperitoneoscopic techniques were taught by eminent leaders and pioneers in minimally invasive urological surgery by faculties from Europe, India and China, including Professor Jens Rassweiller, Professor Christian Schwentner (@Schwenti1977), Dr Domenico Veneziano (@d_veneziano), Professor Janak Desai (@drjanajddesai), and Professor Zhang Shudong.

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Joint UAA-ESU 3D laparoscopic and endourological skills course faculties. Left to right: Dr Ada Ng (Hong Kong), Dr Wayne Lam @WayneLam_Urol (Hong Kong), Professor Janek Desai @drjanajddesai (India), Professor Jens Rassweiller (Germany), Professor MK Yiu (Hong Kong), Dr James Tsu (Hong Kong), Dr WK Ma (Hong Kong).

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Joint UAA-ESU 3D Laparoscopic skills workshop – Above: Professor Rassweiller (Germany) supervising overseas delegates. Below: Professor MK Yiu (Hong Kong) demonstrating techniques of laparoscopic suturing to delegates from China.

The renal cell carcinoma #RCC masterclass was a particular highlight. A whole day of excellent lectures and speakers entertained both local and international delegates, and was particularly popular with trainees. There were talks examining the role of percutaneous biopsy of renal tumours presented by Alessandro Volpe (@foxal72), an update of current trends and techniques in robotic and laparoscopic partial nephrectomy by Dr. Joseph Wong (Hong Kong) and Dr. Shuo Wang (China) and a fantastic discussion examining the role of non-clamping partial nephrectomy by Dr. Ringo Chu (Hong Kong). The afternoon session kicked off with @nairajesh giving a comprehensive review on the surgical management of advanced #RCC. Professor Axel Bex (Netherlands) continued with an examination of neoadjuvant and adjuvant systemic therapy in #RCC and the emerging role of #immunotherapy. Professor Alessandro Volpe (@foxal72) discussed the current #EAU guidelines and recent updates.

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Masterclass in #RCC: @foxal72 , @nairajesh , Professor Axel Bex (Netherlands), with moderators Dr Ringo Chu (Hong Kong) and Dr Joseph Wong (Hong Kong).

 

Day 1 of #UAA2017

The plenary session on day 1 of #UAA started off with Professor Zengnan Mo from China on the epidemiology of prostate cancer in Asia. There is, not surprisingly, a very diverse range of incidence of #prostatecancer rate across the largest continent in the world, inevitably effected by the presence of #PSA screening in countries such as Japan and Korea, ethnicity (East Asia vs Middle East), genetics (Israeli Jewish population), and their local healthcare system and policies. Arguably the currently available #prostatecancer screening trials may not be applicable to the Asian populations, and various on-going studies in Japan and China are going to address these issues. One in particular is an ongoing population-based study funded by the Chinese Ministry of Science and Technology, in which over 50,000 men will be recruited into the screening, early detection, localised, and advanced #prostatecancer cohorts and to be followed up with time. Obviously, we will not expect to see the results of the trial anytime soon, but will surely answers to address the behaviour of prostate cancer in the Asian population in the future.

Professor Sam Cheng (@UroCancerMD) from Vanderbilt University then gave a comprehensive review on the current status of #cystectomy. Robotic cystectomy appears to have the benefit of reduced blood loss and length of stay. However, long-term oncological outcome still remains uncertain, and certainly, patient reported outcome measures (PROMs) is lacking.

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Day 2 of #UAA2017

After early showers on day 2 of UAA, Hong Kong was heating up with temperatures over 33 degrees Celsius. So were the discussions in the plenary session in the morning. Professor Freddie Hamdy (@Freddie_Hamdy) gave the #EAU lecture on #activesurveillance for #prostatecancer. This was followed on nicely with the current status of #prostatecancer management in Hong Kong by Dr. Yau-Tung Chan and Dr. Gerhardt Attard (UK) enlightened the audience with a concise update in the management of hormone sensitive prostate cancer, an area where the landscape is ever-changing.

The advanced oncology session started off with a heated debate in the use of mass clamping (Dr Ringo Chu, Hong Kong) versus selective artery clamping in partial nephrectomy (Dr Tae-Gyun Kwon, Korea). Both speakers presented with very valid arguments and perhaps it was fair to say it ended up with all square. Professor Krishna Sethia (UK) gave a fascinating summary of the current local management of #penilecancer at centralised penile cancer centres in the UK, after which I was honoured to provide an update on current nodal management in #penilecancer from my recent experience at St George’s University Hospitals @StGeorgesTrust in the UK. It was exciting to see the centralisation of services in #penilecancer in the UK has given great opportunities to understand and optimise management of patients with such rare disease.

The Semi-live sessions entertained the audience on both days of the conference. Excellent videos were presented throughout. Professor Koon Rha of Yonsei University in South Korea gave a fantastic semi-live talk on his tricks and techniques of Retzius-space sparing Robot-assisted radical prostatectomy. Perhaps what’s even more exciting to know is that a Korean company has produced a new robot for surgery which has been well tested by Professor Rha’s group, which has just literally been licenced and approved in Korea just days before #UAA2017. Will this finally drive the cost of robotic surgery down? Time will tell.

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Associate Professor Declan Murphy (@declanmurphy) and Mr. Rajesh Nair (@nairajesh) both contributed with a beautiful video showcasing techniques in total pelvic exenteration and long-term outcomes of urinary diversion and reconstruction in this cohort of patients.

The Gala dinner in the evening was full of fun and entertainment. Following the performance of a soprano quartet formed by local Hong Kong urologists (who sang the classic My Way with a twist on prostate examination!), the rock stars of urology – Professor Jens Rassweiller, Dr Samuel Yee from Hong Kong, and Dr Domenico Veneziano (@d_veneziano) provided an energetic and electrifying live performance of some rock classics!

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Urology Rock N’ Roll! Left to right: Professor Jens Rassweiller (Germany), Dr Domenico Veneziano (Italy), Dr Samuel Yee (Hong Kong).

However, perhaps the highlight and the most touching moment of the evening the performance of a song written and sung by a young local former patient with a history of #ketaminebladder , who was successfully treated by the urology team lead by Professor Anthony Ng at the Prince of Wales Hospital in Hong Kong. His surgery and treatment has transformed his life – he is now enjoying a career as both a singer-songwriter of a rock band and as a footballer!

 

Day 3 of #UAA2017

The morning plenary session also saw the evergreen Dr Peggy Chu of Hong Kong, renown for her discovery of ketamine-associated uropathy and pioneered the management of this challenging 21st century urological disease.

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Left to right: Dr CW Man (Hong Kong), Congress President of #UAA2017, and Dr Peggy Chu (Hong Kong).

She delivered a very interesting talk on revisiting the role of #gastrocystoplasty. Interestingly, the operation was first described and carried out in human by the honourable Professor CH Leong at my current institution, Queen Mary Hospital @HKUniversity , in the 1970s following a successful animal study at the same institution. Its use has been limited due to its associated metabolic disturbances, but arguably it is still a weapon that can be used when tackling patients with tuberculosis-associated severely contracted bladder, in particular those who have already been rendered to have a single solitary kidney due to the disease. Another situation when #gastrocystoplasty can still be considered are those patients with #ketamine uropathy. Although patients are usually required to be completely abstinence from #ketamine abuse for a certain lengthy period of time before they are eligible for surgical treatment, many fear the avalanche effect of ileal re-absorption of the drug if an ileo-cystoplasty has been carried out in these patients, if they happen to resume ketamine use in the future. Hence, #gastrocystoplasty may be a better substitution tissue for cystoplasty in the management of such patients.

The meeting also provided an opportunity to catch up with fellow Guy’s Hospital urology graduates @nairajesh and @declanmurphy over a cold pint of Hong Kong locally made #MoonzenBeer, when the temperature outside the conference centre was hitting 34 degrees Celsius!

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Left to right: Dr Wayne Lam (Hong Kong), Mr Rajesh Nair (Australia/United Kingdom), A/Prof Declan Murphy (Australia).

All credits to #UAA and the local organisers’ immense effort and hard work, making this congress a valuable learning experience for everyone who participated. We very much look forward to #UAA2018. Bring on Kyoto, Japan!

 

 

Wayne Lam

Assistant Professor in Urology, Queen Mary Hospital, University of Hong Kong

Twitter: @WayneLam_Urol

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Rajesh Nair

Fellow in Robotic Surgery and Uro-Oncology

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The British are coming!

bju13868-fig-0001Historians report that Paul Revere never said these famous words; as Colonial Americans at the time still considered themselves British. Indeed, Americans still consider themselves European. The United States Census reports that 73% of Americans are of European descent, and 62% of these are of English, Scottish, Welsh or Irish ancestry.

These links to our heritage remain strong. With >1100 European members (close to 200 from the UK) and >300 members from Australia and New Zealand, our bonds of friendship and collaboration are tightly intertwined. So if Paul Revere won’t say it, I will!

The British are coming! Each year >2000 Europeans attend our Annual meeting (200 from the UK) and >100 from Australia and New Zealand. They are represented not only in quantity but also in quality. Of the 1700 scientific abstracts submitted from Europe to the 2017 Annual meeting, the acceptance rate was 38% for the UK, compared to an overall acceptance rate of 34%. Important science comes from the UK and Australia, and raises the quality of our meeting.

The BAUS–BJUI–USANZ Joint Session on Sunday 14 May in Boston is a clear example of how the BJUI family, as the official journal of the USANZ and the BAUS ‘raises the bar’ at the AUA Annual Meeting. With focuses on personalised medicine, genomics, systems biology, immunotherapy, and ‘training the brain’, it promises to stimulate and educate. Following this we look forward to toasting our transatlantic brothers and sisters with a Boston Lager at the BJUI reception.

The British are coming! We look forward to welcoming you in Boston in May.

Manoj Monga, AUA Secretary
Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA

 

Immunotherapy in urological malignancies: can you take your knowledge to the next level?

bju13648-fig-0001In this month’s issue of the BJUI, we highlight the evolving era of immunotherapy in solid tumour therapy. As urological surgeons, we spend a large portion of our time working with anatomy, instruments, and robots – things we can see, touch, and control. Immunotherapy is a different conversation – cartoon pathways, process blockades, molecular expression levels, combination therapies, and treatment resistance. Curing a patient with a successful operation is a major draw to our field, but we know our limitations when faced with lethal variant prostate cancer, and high-grade/high-stage bladder and kidney cancers in particular. Systemic therapies have been around for decades and are part of our guidelines – so why all the excitement over immunotherapy?

Our highlighted articles are a review from Mataraza and Gotwals [1] and a comment from Elhage et al. [2]. I urge you to start with the review article [1] and give it a full line-by-line read. You may need to pull out pen and paper, and practice spelling and pronouncing a number of new compounds. They may sound as awkward as abiraterone did the first time you heard of it years ago but will eventually become familiar and attached to yet another catchy trade name from pharma. Here is a quick list/homework assignment: ipilimumab, nivolumab, pembrolizumab, pidilizumab, atezolizumab. Another 20 or more are in development. Challenge yourself to write out their pathways, and you may re-learn a thing or two about familiar agents like sipuleucel-T, interferon α, and interleukin 2.

A major theme in both articles is the experience with immunotherapy in advanced melanoma. The enticing message is that a cohort of patients with metastatic melanoma treated with ipilimumab survived 3 years and the Kaplan–Meier curves plateau out to 10 years. This observation sparks different possible futures such as immune ‘memory’, durable response, and ultimately the word we like to use in surgery – cure.

The picture in urological cancers is not entirely as rosy as the melanoma Kaplan–Meier curve. Multiple trials are highlighted by our review with familiar themes of single agent trials, combination immunotherapies, and combined immunotherapy plus anti-angiogenesis agents. Many trials enrol heavily pre-treated populations with limited remaining options. Many endpoints still observe responses followed by resistance patterns. An important theme to follow is the coupling of biomarkers that link expression to treatment response (i.e. predictive vs prognostic), and the USA Food and Drug Administration (FDA) has approved such a biomarker for nivolumab response. However, even this story line is perplexing, as drug response is not always linked to the marker, and immune cell expression may be ‘inducible and dynamic’ [1].

Last step – re-read the review and comment articles and see if you can write down some key agenda items for future immunotherapy. How are checkpoint inhibitors different from vaccines? How do we generate a durable immune response? What is the ‘abscopal effect’? What are three major areas of research and development in immunotherapy?

If you can spend the time on these articles and ponder these challenging questions, you will move up to the next level of understanding and enjoy a greater appreciation of the next abstract you hear at a major meeting. In closing, I am reminded of the oft-repeated words from the hit television show Game of Thrones (based on the novels of George R.R. Martin) from the House Stark: ‘Winter is Coming’. In urological oncology, ‘Immunotherapy is Coming’, so be prepared!

 

John W. Davis

BJUI Associate Editor Urological Oncology

 

References

1 Mataraza JM, Gotwals P. Recent advances in immuno-oncology and its application to urological cancers. BJU Int 2016; 118: 50614

 

2 Elhage O, Galustian C , Dasgupta P. Immune checkpoint blockade treatment for urological cancers? BJU Int 2016; 118: 498505

 

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