MAKE AN ENDURING
Although cisplatin-based chemotherapy remains the recommended frontline option for cisplatin-eligible patients with mUC,[i] immunotherapy with TECENTRIQ is a treatment option in the first-line setting for cisplatin-ineligible patients whose profile have a PD-L1 expression ≥5%.3
Urothelial cancer is an aggressive malignancy with poor prognosis
In the metastatic setting, urothelial cancer is associated with a 5-year survival of just 5%.1
TECENTRIQ is approved for a broad range of patients with locally advanced or mUC3
TECENTRIQ as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC):3
- After prior platinum containing chemotherapy, or
- Who are considered cisplatin ineligible, and whose profile have a PD-L1 expression ≥5%
IMvigor210: A Phase 2 efficacy trial in first-line mUC4
A Phase 2, two-cohort study in patients with locally advanced or mUC (N=429) who were ineligible for cisplatin (n=119) or had received prior platinum therapy (n=310) received TECENTRIQ until unacceptable toxicity or disease progression. Primary endpoints included ORR and DOR.
TECENTRIQ: the first cancer immunotherapy approved in first-line PD-L1+ cisplatin-ineligible mUC
IMvigor211: A Phase 3 efficacy trial in pre-treated mUC6
A Phase 3 study in patients (N=931) with locally advance or mUC progressing on platinum-containing regimens received either TECENTRIQ (n=467) or investigators’ choice of 3 treatments (n=464) until unacceptable toxicity or disease progression. OS was the primary endpoint.
TECENTRIQ delivers a durable response in first-line and pre-treated mUC
What this means for patients with mUC
View video transcript
Dr Axel Merseburger
My name is Axel Merseburger, and I'm honoured to present to you the just recently published data on SAUL, which has been published in European Urology and shown at the EAU Congress just recently in Barcelona, Spain. SAUL is a prospective phase III trial on atezolizumab in real-world patients in metastatic urothelial carcinoma.
The patients were treated with atezolizumab in the standard dose every three weeks, and primary endpoint is set as safety with a lot of interesting secondary endpoints like overall survival, progression-free survival as shown in this slide.
In this slide you see the baseline characteristics of the treated patients. As you can see here, we really have real-world population.
In this slide we see the most common adverse events, more than 10%. Uniquely, we displayed all the adverse events, not only the treatment-related. However, at the bottom of the slide you see the treatment-related grade 4 and 5 adverse events, which are few. So atezolizumab, in conclusion, is well tolerated in this special study population.
Here you see the overall survival, a secondary endpoint after a median follow-up of 12.7 months, which is still pretty short, the chosen overall survival of 8.7 months, and 41% are still alive after 12 months of treatment, after the first year. So also a good signal with regards to the secondary endpoint overall survival.
On the right you see we have not reached the median duration of response. However, disease control rate is 40%.
Here you see the safety overview of subgroups with special interest. In general, we're looking at the numbers atezolizumab treatment is well tolerated. In the bar on the bottom you see that discontinuation rate in those subgroups is very low.
Here we see a visualisation of overall survival in the subgroups of special interest. The 10% of patients with ECOG performance status 2 are difficult to treat, and we see here that they did less well than the overall population. On the other hand, patients without immune disease seemed to do very well on atezolizumab.
Here you see the efficacy in the IMvigor211-like population. In the slide we really tried to identify the patients that would have been eligible for the IMvigor211 trial, so not the patients having special conditions. You see in this trial population we reached a median overall survival of 10.0 months. After one year, 12 months OS, 46% of the patients were still alive.
Here we see the overall survival in the SAUL trial in context of randomised phase III trials, surely acknowledging the limitation of this indirect comparison.
In conclusion, SAUL is the largest prospective clinical trial in immunotherapy in advanced urinary tract carcinoma. We have demonstrated that atezolizumab is tolerable and effective treatment even in complex and comorbid patient populations. Efficacy overall and in the IMvigor211-like subgroup is inconsistent with previous pivotal trials on PD-L1 and PD-1 inhibitors in urothelial carcinoma.
These results support the use of atezolizumab in urinary tract carcinoma, including patients with limited treatment options.
View video transcript
“The results of SAUL support the use of atezolizumab in urinary tract carcinoma, including in patients with limited treatment options.”
Prof. Axel Merseburger
View video transcript
I'm 73 in July.
I come from South-West England. And I'm a survivor of bladder cancer. TCC to be precise. The first hint that I had a problem was at Christmas Eve 2008. And I went to the toilet, and my urine was blood-coloured, was red. You get very frightened. You’re worried. I've never been ill in my life. I’ve always been fit and strong.
But it being Christmas Eve, doctors are closed. Hospitals are virtually closed. Two or three days after Christmas, we went to the doctor. And the doctor says, well, we’ll so a lot of tests. Don’t worry, it can be 50 different things. It might not be cancer, don’t worry about it.
Your whole emphasis of your life turns around with that sudden shock in the second or two of the diagnosis coming through and saying it’s cancer. It took them about six weeks to find the tumour. And then I was told that I had to go in and have a kidney removed because my cancer was outside the bladder, touching the kidney, and on the tube coming out.
So, after about eight or nine months, your cancer hasn't gone at all. It’s back again.
So, now you're into options. What have we got? Well, let’s go for more surgery. Another eight-hour surgery. Eight hours. The first one was nine hours. The second one was eight hours. And the doctor comes, the surgeon comes, and says well, I think we’ve got it all, Dave. We’re not sure, but we think we have. We think we might cure it with chemo.
Okay. Okay. So, then you start on a course of chemo. I don't know what was worse, the cancer or the chemo. The only way I can describe chemo is you know when you've had your worst hangover and you wake up the next afternoon, trying to remember your name, wondering where the hell you are. That's what it feels like when you’re having chemo. Only, when you have chemo, you feel like that every day for four months.
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“I have got quality of life now…. I plan a summer holiday”
Dave, patient suffering from bladder cancer
References & Notes
References & Notes
1 National cancer institute surveillance, epidemiology, and end results program. SEER cancer statistics factsheets: Bladder cancer. Available from: http://seer.cancer.gov/statfacts/html/urinb.html (Accessed April 2020).
2 Flaig TW, et al. NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer. Version 2.2020. Available from: www.NCCN.org (Accessed April 2020).
3 TECENTRIQ (atezolizumab), Summary of Product Characteristics. 27 March 2020. Available from: https://www.medicines.org.uk/ (Accessed April 2020).
4 Balar AV, et al; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: A single-arm, multicentre, Phase 2 trial. Lancet. 2017;389:67–76.
5 Powles T, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): A multicentre, open-label, phase 3 randomised controlled trial [published correction appears in Lancet. 2018;392:1402]. Lancet. 2018;391:748–57.
6 Powles T, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): A multicentre, open-label, phase 3 randomised controlled trial [published correction appears in Lancet. 2018;392:1402]. Lancet. 2018;391:748–57.
7 Van der Heijden M, et al. Atezolizumab (atezo) vs chemotherapy (chemo) in patients (pts) with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): A long-term overall survival (OS) and safety update from the phase III IMvigor211. Ann Oncol 2019;30 (suppl 5):v356–v402.
8 Sternberg CN, et al. Primary results from SAUL, a multinational single-arm safety study of atezolizumab therapy for locally advanced or metastatic urothelial or nonurothelial carcinoma of the urinary tract. Eur Urol. 2019;76:73–81.