麻豆传媒

Adding the PD-L1 inhibitor atezolizumab (Tecentriq) to standard neoadjuvant therapy with gemcitabine and cisplatin showed promising efficacy in patients with muscle-invasive bladder cancer (MIBC), according to data from a phase II trial presented at the 2021 virtual .

In this exclusive 麻豆传媒 video, , associate professor of clinical urology at the University of Southern California Keck School of Medicine, discusses findings from .

Following is a transcript of his remarks:

This study has been using the combination of one of the novel agents that was approved for metastatic urothelial carcinoma, called atezolizumab, which works on the PD-1/PD-L1 pathway and combines it with the standard-of-care systemic therapy, which is gemcitabine/cisplatin, in neoadjuvant setting before cystectomy. And they tried to see the effect of it on the pathologic response of radical cystectomy in these patients.

This was a phase II study and it's basically more focused on feasibility and safety. In this study, they actually enrolled all the patients with cT2-T4aN0 ... and they gave them atezolizumab 1,200 mg IV for 2 weeks. They gave atezolizumab first, with the 1,200-mg IV dose first, and then 2 weeks later started the neoadjuvant chemotherapy, the 4 cycles of gem-cis.

And every 3 weeks during this chemotherapy, they were getting the atezolizumab. And even after finishing the chemotherapy, if there was a gap until the surgery, which the majority of them got the surgery within 2 months, the median time to get that was about 7 or 8 weeks to get cystectomy, they still got another dose of atezolizumab.

The primary endpoint was downstaging, which means the final pathology is <pT2N0, and the secondary endpoints were complete response, which was pT0N0, recurrence-free survival, and safety.

So 44 patients actually were enrolled to this study and 39 were evaluable. And out of these 39 undergoing neoadjuvant combination of therapy followed by radical cystectomy, 27 out of those 39, which is almost 70%, showed downstaging. And 17 out of 39, which was almost 44%, showed complete response, meaning pT0N0. Seven patients actually had positive lymph nodes as well in the final pathology, so definitely some patients did not respond or progress.

The median follow-up was about 16 months. And so they really couldn't comment on the recurrence-free survival, but definitely they saw a very good response in terms of downstaging, as well as complete response. This is way better than previous reports on chemotherapy alone in the neoadjuvant setting.

In terms of toxicity profile, actually I noticed that it's not too bad. A majority of the toxicity and side effects were from the chemotherapy. The general side effects you see grade 3 or 4 neutropenia, lymphopenia, anemia. Some [immunotherapy]-related complications also were reported: asymptomatic pancreatitis and symptomatic pancreatitis, hepatitis in one or two patients. Really, really minor [events] were reported.

Also, 10% of the patients were reported to be positive for PD-L1 downstaging, which is different from previous reports for metastatic urothelial carcinoma, as well as muscle-invasive disease, but again, a small number of the cohort, so that we may not be able to comment on that really strongly.

I think what we really can get from this study and is important is that the response to combination therapy in neoadjuvant setting, i.e., chemotherapy plus immunotherapy in this setting, has shown promising results in terms of downstaging, as well as complete response following radical cystectomy.

Also, another important point is that this combination is not associated with a significant change or increase in the toxicity profile of these therapies. I think the other result probably from this study is the median follow-up was about like 16, 17 months, not enough to talk about the recurrence-free survival, which was one of the secondary endpoints, but especially from durability of those who responded, they noticed that those who responded, they were durable for 1 year.

So it's effective, it's not associated with significantly increased toxicity profile, and it's actually durable when it responds. So I think this has been really the best outcome we can expect in this issue. And certainly I think there's still more room to work. I believe we still have more than 30% of the patients, almost 30%, who do not downstage. And we know that the prognosis is not great in these patients. And we really don't have a good tool to predict who is not going to respond and who is going to respond.

So I think that's where we should work. Plus there has been more novel agents in the era of targeted therapy and immunotherapy that nowadays especially is being used in metastatic [disease], and there are, right now, trials being tested in the neoadjuvant setting plus or minus chemotherapy.

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