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During the 2025 ASCO Genitourinary Cancers Symposium, Oncology Decoded held their inaugural podcast with a live filming taking place at the conference. The first episode focused on bladder cancer specifically, neoadjuvant vs adjuvant therapy options and the use of cisplatin vs carboplatin.

Meet the expert panel involved in the discussion:

Manojkumar Bupathi, MD, MS, executive co-chair of Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute; medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers;

Benjamin Garmezy, MD, associate director of Genitourinary Research and executive co-chair of Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI); medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers;

Petros Grivas, MD, PhD, professor in the Clinical Research Division and clinical director of Genitourinary Cancers Program at Fred Hutch Cancer Center;

David Morris, MD, MS, president of Urology Associated, PC.

During the discussion on neoadjuvant therapy, the panelist brought up results from the phase 3 NIAGARA trial (NCT03732677) which assessed durvalumab (Imfinzi) along with radical cystectomy and adjuvant chemotherapy followed by radical cystectomy.

For those who achieved a pathological complete response (pCR), the median overall survival (OS) was not reached (NR) in the durvalumab arm or the comparator arm (HR, 0.72; 95% CI, 0.387-1.426). For those who did not have a pCR, the median OS was NR in both arms as well (HR, 0.84; 95% CI, 0.660-1.068). The intent-to-treat (ITT) population OS HR was 0.75 (95% CI, 0.59-0.93).

In the ITT population, the pCR was 37.3% (95% CI, 33.2%-41.6%) in the durvalumab arm and 27.5% (95% CI, 23.8%-31.6%) in the comparator arm (OR, 1.60-1.23-2.08).

Results from this trial then led into the use of cisplatin vs carboplatin. From a urologist perspective, Morris notes that all patients should be afforded the opportunity for neoadjuvant therapy vs being thrown right into surgery. He also mentions this scenario can occur because of the criteria for administering cisplatin.

“If I had one message today for our friends and colleagues in practice, do not use carboplatin in the neoadjuvant setting. If you can give cisplatin, we can talk about who can be cisplatin-eligible. If you cannot give cisplatin safely, the options could be radical cystectomy upfront with liminal dissection or clinical trial, if available and eligible, and bladder preservation can be another strategy in these patients,” Grivas said.

Grivas backed up his reasoning here because of clinical trials that have been conducted regarding pCR rates. These rates appeared to be lower in those given carboplatin vs those given cisplatin. Because of this, he will not use carboplatin as a neoadjuvant or adjuvant approach for muscle-invasive bladder cancer.

Moving forward, they hope to focus on capturing additional data from real-world studies as well as more trials to provide evidence-based research for the treatment of bladder cancer.

Galsky M, Van Der Heijden M, Catto J, et al. Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA. J Clin Oncol 43, 2025 (suppl 5; abstr 659).

, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

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The Oncology Decoded podcast highlighted the impact of the results from the NIAGARA trial for patients with bladder cancer in a post-ASCO GU discussion. 

NIAGARA Study is the Forefront of Post-ASCO GU Discussion in Bladder Cancer

CancerNetwork® spoke with Jun Gong, MD, a practicing medical oncologist who specializes in the treatment of genitourinary cancers at Cedars-Sinai Medical Center, regarding a perspective piece he wrote titled, “

Cisplatin Neoadjuvant Chemotherapy in an Aging Population With Muscle-Invasive Bladder Cancer

Gong’s perspective analyzes and builds upon a study featured in the January issue of 

Use of Neoadjuvant Chemotherapy in Elderly Patients With Muscle-Invasive Bladder Cancer: A Population-Based Study, 2006-2017

In this conversation, Gong provided an overview of the research and touched on some of the clinically relevant findings. He then expanded on the use of cisplatin-based chemotherapy in an aging population, how age fits into the treatment equation, and where research should focus moving forward in muscle-invasive bladder cancer.

Don’t forget to subscribe to the “Oncology Peer Review On-The-Go” podcast on Apple Podcasts, Spotify, or anywhere podcasts are available.

Jun Gong, MD, spoke with CancerNetwork® about the latest research from the journal ONCOLOGY® on elderly patients with muscle-invasive bladder cancer.

Oncology Peer Review On-The-Go: Neoadjuvant Chemotherapy for Elderly Patients with Muscle-Invasive Bladder Cancer

Today we are discussing immunotherapy approaches for the treatment of advanced urothelial cancer with Dr. Petros Grivas, MD, PhD, a medical oncologist who focuses on genitourinary cancers at the Seattle Cancer Care Alliance and the University of Washington. Grivas is an associate professor and clinical director of the Genitourinary Cancers Program at the University of Washington, and associate member of the Fred Hutchinson Cancer Research Center in Seattle. 

There have been at least five Food and Drug Administration (FDA) approvals of immunotherapies, and specifically of immune checkpoint inhibitor antibodies, for urothelial cancer. Could you briefly go through the agents now available for treatment and which patients are eligible?

I would start by saying that we have experienced a revolution in the treatment landscape for advanced urothelial cancer in the last few years and this has led to the FDA approval of five distinct immune checkpoint inhibitors that inhibit the PD1/PDL1 axis of the immune system. These five agents are pembrolizumab, atezolizumab, durvalumab, avelumab and nivolumab.

All of these agents are approved for patients who have advanced urothelial cancer, meaning locally advanced/unresectable or metastatic disease and have progressed despite treatment with platinum-based chemotherapy. These agents are approved by the FDA in what we call the “salvage setting” after prior platinum-based chemotherapy.

One of those agents, pembrolizumab, has shown overall survival benefit, as a primary endpoint of a phase 3III trial, compared to salvage chemotherapy in patients who progressed on platinum-based chemotherapy. The other agents were approved based on phase II trials. It is worth mentioning that another agent, atezolizumab, was also tested in a phase III trial that showed that in “all-comers," meaning in the entire study population, there was overall survival benefit compared to salvage chemotherapy.

However, this was not the primary endpoint; the primary endpoint was overall survival in the subset of patients who had higher PD-L1 expression and this particular primary endpoint was not met in this IMvigor211 trial.

So overall, we have five agents approved in this particular salvage setting, and one of them has Level 1 evidence based on NCCN [National Comprehensive Cancer Network] guidelines based on the phase III Keynote 045 trial, that compared pembrolizumab vs salvage chemotherapy. However, all of these therapy options are approved and available in this setting, but there is no data to use one after progression on another checkpoint inhibitor.

Moreover, in the first-line setting, especially for cisplatin-unfit patients, meaning patients who cannot safely receive cisplatin in the first-line, chemotherapy-naÃ¯ve for advanced disease setting, two of these agents are FDA approved: atezolizumab and pembrolizumab based on single arm, phase II studies (IMvigor 210, cohort 1, for atezolizumab, and Keynote 052 for pembrolizumab). These agents were initially approved regardless of tumor tissue PD-L1 expression.

However, more recently, around May and June of 2018, there were discussions with the FDA and EMA (European Medicines Agency) in Europe that ultimately led to the modification of the label of these two agents in the first-line setting. The chemotherapy naÃ¯ve cisplatin-unfit patients that restricted the use of these two checkpoint inhibitors to patients with high PD-L1 expression based on the companion corresponding assay for each agent.

For example, for pembrolizumab, this is the Agilent/Daco 22C3 assay, and for atezolizumab, the Ventana SP142 assay. However, in the US based on FDA clarification, if a patient is very frail and unfit for carboplatin, so not a good fit for any platinum-based chemotherapy, there is no need to check PD-L1 expression in these patients and they could get either approved checkpoint inhibitor in the first-line setting regardless of PD-L1 expression.

These are the approved agents, but there are a plethora of ongoing clinical trials that are looking at combination therapies in advanced urothelial cancer, while also looking at biomarkers. There is also evaluation of those and other immune checkpoint inhibitors in earlier disease settings, including the adjuvant and neoadjuvant settings as well as the non-muscle invasive bladder cancer setting.

You mentioned cisplatin-based chemotherapy has been the standard of care for urothelial carcinoma. In the context of the labels for the approved checkpoint inhibitors, how do you view the role of these agents in treatment? Are there also other options for the same line of therapy? How do you choose an immunotherapy vs a different type of treatment for patients?

There are a few points to make here. Number one is that in the front-line setting in the locally advanced/unresectable or metastatic urothelial cancer, the standard of care is cisplatin-based chemotherapy. Of course, we always want to do clinical trials and this is the optimal way to go regardless of treatment setting. But in the absence of trials, cisplatin chemotherapy, usually gemcitabine-cisplatin, or less frequently, accelerated, dose dense MVAC [methotrexate, vinblastine, doxorubicin, cisplatin] is used in this first-line setting.

The patients who cannot get cisplatin have the option of getting non-cisplatin chemotherapy and usually many of those patients end up getting carboplatin/gemcitabine or a checkpoint inhibitor, pembrolizumab or atezolizumab, which, as we just discussed, are approved in this first-line “chemotherapy naive for advanced disease” setting for cisplatin unfit patients. The decision depends on the fitness, candidacy, eligibility for cisplatin, and the availability of clinical trials. Right now, in advanced urothelial cancer we have chemotherapy and immunotherapy as approved options.

We don't have any other agents approved yet, however, we have many ongoing clinical trials looking at antibody drug conjugates. Agents like enfortumab vedotin and sacituzumab govitecan, which are being tested in very interesting phase II and III trials, with prior, early-phase, trial data looking very promising.

There are also targeted therapy trials, including inhibitors against FGF receptor, PARP, HER2, and other molecular targets. I think that these trials are very interesting, and hopefully we will have more agents approved in the future. Until then, I think clinical trials is the optimal way to go.

To summarize, cisplatin-based chemotherapy upfront is the standard of care for fit patients. For cisplatin-unfit patients we have either other chemotherapy, for example carboplatin/gemcitabine, or the two approved checkpoint inhibitors as first line therapy, based on the details we discussed above.

If a patient is progressing on platinum-based chemotherapy, a clinical trial is again the way to go. Outside of clinical trials, we have the five FDA-approved checkpoint inhibitors, with pembrolizumab having Level 1 evidence in this salvage therapy setting.

You mentioned that there are clinical trials of combinations and there are trials testing these immunotherapy agents in earlier disease settings, and also biomarkers. Of all of these questions that you and your colleagues are addressing with respect to checkpoint inhibitor antibodies, are there one or two questions that you could highlight?

I think there are multiple, very interesting clinical trials, really a huge list, and I don’t want to leave anything out. But overall, the main questions we are trying to answer are in the first-line setting, is chemotherapy or immunotherapy the way to start for advanced urothelial cancer?

In that context, there are four large, phase III trials asking this question of chemotherapy vs immunotherapy in the front-line setting. Two of these trials are asking an additional question, which is whether the combination of chemotherapy and immunotherapy is better than chemotherapy or immunotherapy alone. I think these trials may potentially impact the treatment landscape.

There are also two very important “switch maintenance” trials. One is a phase III trial that is testing an anti-PDL1 agent, avelumab), after 4 to 6 cycles of front-line platinum-based chemotherapy, with no progression. Patients get randomized to avelumab and best supportive care vs best supportive care alone.

There is also a phase II trial that has a very similar design that is randomizing patients to pembrolizumab vs placebo with a crossover design after front-line platinum-based chemotherapy to evaluate this “switch maintenance” question, whether this sequencing of therapies is of benefit. As I mentioned, there are numerous other trials with a plethora of agents, checkpoint inhibitors plus chemotherapy, radiation therapy, targeted therapies, antibody drug conjugates, vaccines, other immune related molecules, cytokines, epigenetic modulators, anti-angiogenesis agents, etc., that are all very interesting.

These trials are trying to build upon what we have already seen with checkpoint inhibitors and are trying to prospectively evaluate the clinical utility of biomarkers. The question is, could we try to select the right patients for the right treatment in the future? Because “one size may not fit all” and patient selection is critical. So far, with the exception of tumor tissue PD-L1 in the front-line setting, we do not have clinically useful biomarkers in advanced urothelial cancer.

There is definitely the opportunity to try to identify clinically useful biomarkers to select patients, but this requires multi-center collaborations and prospective validation of candidate biomarkers across clinical trials. This is something very hard to do, but we should all push through. Candidate biomarkers span across tumor tissue, urine and blood-based biomarkers, which are interesting and worth exploring further.

Thank you so much for joining us today Dr. Grivas.

My pleasure. Hopefully we will experience many more advances in the near future in the field of urothelial cancer with new agents and biomarkers.

Grivas has done consulting with Genentech, Merck & Co., Pfizer, Bristol-Myers Squibb, AstraZeneca, Biocept, Clovis Oncology, EMD Serono, Seattle Genetics, Foundation Medicine, Driver Inc., QED Therapeutics, Heron Therapeutics, and Janssen within the past 2 years. He was previously involved in an educational, unbranded program with Genentech and Bristol-Myers Squibb. His institutions have received research support from Genentech, Bayer, Merck & Co., Mirati, OncoGenex, Bavarian Nordic, Pfizer, AstraZeneca, Clovis Oncology, and Immunomedics.

Cancer Network spoke with Dr. Petros Grivas about emerging immunotherapy approaches for the treatment of advanced urothelial cancer.

Emerging Immunotherapy Approaches For Urothelial Cancer

Ahead of the American Association for Cancer Research annual meeting, being held April 14–18 in Chicago, Illinois, we spoke with Elizabeth Plimack, MD. Dr. Plimack is chief of the division of genitourinary medical oncology and director of genitourinary clinical research at the Fox Chase Cancer Center in Philadelphia, where she specializes in the treatment of genitourinary cancers, including bladder cancer. At the meeting, she will be discussing recent advances in systemic therapy for bladder cancer, in a presentation entitled, “Systemic Therapy for Locally Advanced and Metastatic Bladder Cancer: A Rapidly Evolving Landscape.”

First, can you talk about the standard surgical and therapy options for locally advanced disease that have been around now for a while, and then how these contrast with the options for metastatic bladder cancer patients?

Sure. Bladder cancer has a variety of presentations. And in fact, the majority of people who develop bladder cancer have what is called noninvasive or localized bladder cancer, which can be treated with topical instillations and procedures done to the bladder itself.

Beyond that, there is a subset of patients with muscle-invasive bladder cancer, and that is what we talk about as locally advanced bladder cancer. Those patients can be cured of their cancer, but it requires what we call multimodality treatment with both chemotherapy and surgery and, in some cases, chemotherapy with radiation. The difference between that state and the metastatic state is that the locally advanced state we are treating with a curative intent and in the metastatic setting, although treatable, the cancer is not curable.

So the goals of care are different and the treatment paradigm is different. I can speak first about best practices for patients with locally advanced muscle-invasive bladder cancer. The treatment algorithm for those patients is fairly well defined, with multiple guideline groups-NCCN [National Comprehensive Cancer Network], the AUA [American Urological Association], and the European groups recommending chemotherapy prior to surgery to increase the chance of a cure, defined as being disease-free at 5 years. We know that adding chemotherapy prior to treatment (typically surgery), helps. Recently, novel developments suggested that chemotherapy alone may be curative for a subset of patients, perhaps 10% to 30% of patients, and we are finding trials in that space to allow for patients to keep their bladders when chemotherapy is curative. I will be speaking about that in my talk at AACR.

What are some of the new treatment modalities that have recently been approved for either locally advanced or metastatic bladder cancer?

In locally advanced disease, we have developed [potential therapeutic regimens] and have started to enroll in clinical trials, looking to identify complete responders to chemotherapy and allowing for bladder-sparing. Those are the trials that are ongoing but have not yielded data yet. We are waiting for data on the 

 a trial that randomized patients to gemcitabine and cisplatin chemotherapy or dose-dense chemotherapy, and that study will provide really important data on more modern chemotherapy regimens in this curative situation, and [on] response rates and cure rates.

But also, this trial will help us define a number of biomarkers, including the ‘COXEN’ biomarker for which the trial was designed. And again, we are waiting for data on all of those trials. In the metastatic setting, it’s a different story. We have had an explosion of data over the last 3 years, which has defined and changed how we treat metastatic patients. And I will be speaking about that in my talk at AACR as well.

Just as an overview, prior to 2016, the last time a drug was approved for metastatic bladder cancer was in the 1970s, when cisplatin and doxorubicin were approved, which is a really long drought that we had of treatment for metastatic disease. We’ve been dependent entirely on chemotherapy up until that time.

Since 2016, a number of checkpoint inhibitors have been approved in the US, and those are now used in both the frontline and second-line setting for patients with metastatic bladder cancer. I will be speaking in my talk about the comparative data across these different agents, their toxicity profile and what questions still remain in terms of guiding their use. A couple of key points to make about the use of these novel checkpoint inhibitors in bladder cancer once it’s metastatic: There are five of these agents approved; all of them inhibit either PD-1 [programmed cell death 1]or PD-L1 [programmed death-ligand 1] and are all in the same pathway. Those drugs are pemrolizumab, atezolizumab, avelumab, durvalumab, and nivolumab.

While it seems like we have five new options, they really all do the same thing and there is no evidence that after we treat with one, treating with another one of those five will yield responses. So what we have that is growing is a group of patients who have had chemotherapy and had [treatment with] a checkpoint inhibitor who now need a novel therapy. I am particularly excited about data emerging in that space, helping patients either reinvigorate their immune response against their cancer or treat with a non-immunotherapy targeted agent such as a VEGF [vascular endothelial growth factor] inhibitor, an inhibitor of NECTIN-4, a novel antibody drug conjugate; that is currently in clinical trials.

In terms of reinvigorating the immune response for patients whose tumors have evaded their single-agent PD-1 or PD-L1 therapy, there are a couple of really interesting approaches. One is with epacadostat plus pembrolizumab. Epacadostat makes the immune microenvironment more appropriate for immune surveillance and [achieving] an antitumor effect. Then a study we are running here, funded by Stand Up 2 Cancer, is looking at hypomethylation to reinvigorate the immune response both by changing the biology of T-lymphocytes and the immune microenvironment. So we are excited about all of those trials, which are all currently enrolling-and many are in phase III already.

Are there additional therapies you haven’t mentioned, with different mechanisms of action, that are still in development and appear to be promising?

There are many. What is exciting for us in treating urothelial cancer is that this disease was one that was usually avoided in trying to develop new drugs; most of the development went to the more common tumor types. The truth is that bladder cancer is very common and has been very responsive to many treatments. So there has been an influx of interest in developing novel agents for this disease, which is great.

One area that we will be looking at closely is earlier stages of disease, so non–muscle-invasive bladder cancer. Again, most of these patients can be treated with treatments that are directly just to the bladder, but there are a lot of rationales for trying both immunotherapies and targeted agents in this space. Again, ideally, the goal is to cure patients of their bladder cancer with systemic therapy, and make sure that they don’t go to surgery.

Now, if the disease cannot be controlled topically, those patients end up with surgical removal of their bladder. Research in that space is interesting and promising, and some of that data will be presented at AACR.

American Association for Cancer Research Annual Meeting (AACR)

Dr. Elizabeth Plimack discusses her 2018 AACR meeting presentation on recent advances in systemic therapy for bladder cancer.

Systemic Therapy for Advanced Bladder Cancer Evolves

Ahead of the American Society of Clinical Oncology (ASCO) 2017 Genitourinary Cancers Symposium, held February 16–18 in Orlando, Florida, we are speaking with Matthew I. Milowsky, MD, who is the section chief of genitourinary oncology and the co-director of the urologic oncology program at the UNC Lineberger Comprehensive Cancer Center in North Carolina. Dr. Milowsky will give a talk at this year

s meeting providing an overview of the research and clinical progress in urothelial cancer over the last year. 

First, how would you characterize the clinical news in urothelial carcinoma in the last year or so?

It’s really been an extraordinary year. After almost 3 decades of little advancement in the field, particularly as related to patients with metastatic disease, the integration of immune checkpoint inhibitors in the management of patients with advanced bladder cancer has really become a theme over the past year and has led to significant improvements in outcomes for patients.

Can you talk about some of the details of the trials of these agents and also how you see them being used to treat these tumor types?

There have been many trials that have been conducted over the past year and many are planned. Some of the prominent trials are related to several agents. There was the IMvigor 210 study using the anti–PD-L1 agent atezolizumab, with two cohorts of patients, and the CheckMate 275 study utilizing the anti-PD1 agent nivolumab. Those studies have led to US Food and Drug Administration approval of both atezolizumab and nivolumab in patients with metastatic urothelial cancer who have progressed after platinum-based chemotherapy. There is another study (Keynote 45) using the anti-PD1 agent pembrolizumab, which is the first randomized study that has demonstrated a survival benefit for patients in the post-platinum space, as compared to chemotherapy.

There have been other agents as well. An anti–PD-L1 agent, durvalumab, has also demonstrated some exciting results in patients who were previously treated. There is also some interesting data in patients who are unfit for platinum-based chemotherapy, specifically two studies. One being the IMvigor 210 cohort 1 with atezolizumab, and Keynote 52 with pembrolizumab, demonstrating very promising results in patients who historically have had very poor outcomes with standard chemotherapy.

What have we learned about the biology of urothelial tumors that could potentially be applied to better strategies for treatment or maybe that are already being applied?

So we’ve learned quite a bit about the biology of urothelial tumors previously with The Cancer Genome Atlas experience, demonstrating that there are many potential targets for novel therapeutics in urothelial cancer based on genetic alterations that occur within the tumor, and many of those targeted therapeutics are being investigated in the context of clinical trials. There is also rationale for why urothelial cancer appears to be an excellent place to use immune-based therapy. There is a very high mutational burden, going along with other diseases like lung cancer and melanoma that have also demonstrated promising activity with immune checkpoint inhibition.

There are specific subtypes of urothelial cancers that may lend themselves to responding better to immune checkpoint inhibitors. There are RNA subtypes that are similar to the hallmarks of some of the RNA subtypes in breast cancer, specifically the luminal and basal subtypes. And there have also been observations related to DNA damage response gene alterations that appear to confer sensitivity to cisplatin-based chemotherapy, which has been the cornerstone for the management of patients with urothelial cancer over the past several decades. Now we may actually be able to use this type of genetic information to understand who is more or less likely to respond to cisplatin-based chemotherapy.

Lastly, what in your mind are the big questions to address in the next few years?

So, it is extraordinarily exciting, as I started out saying, and I think certainly the immune-oncology space is going to hopefully continue to explode over the next several years. I think we will need to understand more about how to sequence these agents, where best to use them, how to combine them with chemotherapy or targeted therapy. Combinations of immune checkpoint inhibitors-a study, CheckMate 32, was presented by Dr. Padmanee Sharma at the Society for Immunotherapy of Cancer (SITC) 2016 meeting that combined nivolumab and the anti-CTLA-4 agent ipilimumab-those sorts of studies are going to be very exciting.

There are also new immuno-oncology agents that are likely to offer benefit in this disease based on some of the previous things that I mentioned about why urothelial cancer may be particularly susceptible to immune-based therapies. This is really unprecedented in terms of the progress that has been made in such a short period of time in the management of patients with a disease that, again, had very little in the way of progress for close to 3 decades.

Thank you so much for joining us today, Dr. Milowsky.

ASCO Gastrointestinal Cancer Symposium

In this interview we discuss the latest clinical news in urothelial carcinoma, what we’ve learned about the biology of these tumors, and how treatment of this disease has evolved.

Latest Progress in Treating Urothelial Carcinoma

Today we are speaking with Padmanee Sharma, MD, PhD, a physician scientist who specializes in immunotherapy for cancer at the University of Texas MD Anderson Cancer Center in Houston. Dr. Sharma recently gave a talk at the 2016 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held January 7–9 in San Francisco, on predictive biomarkers and response to immune checkpoint inhibitors for urothelial tumors, which include tumors of the bladder, ureters, and the renal pelvis.

First, what are some of the immunotherapies currently being developed for these types of tumors?

The immune checkpoint therapies that are being developed currently are those that block the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitory pathway, as well as the programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitory pathways. These therapies are very important because they have shown that by blocking the inhibitory pathways on T cells, which are the soldiers of the immune system, you can actually get very robust anti-tumor immune responses that lead to regression and, in some patients, even complete disappearance of disease. Since we are blocking pathways on T cells and not tumor cells, tumor types such as melanoma, lung cancer, and kidney cancer have been explored, and they have shown really great results. These immunotherapies are now being explored for urothelial cancers like bladder cancer.

Do we have clinical evidence that some of these urothelial tumors are likely to respond to immunotherapy?

We did one of the first clinical trials at the time, in 2006, with the anti–CTLA-4 antibody ipilimumab and showed that in 12 patients with early-stage bladder cancer, 3 of the patients’ tumors completely went away. They had no tumors at the time of surgery. That was a very early clinical trial. More recently, researchers have been doing clinical trials with anti–PD-1 and anti–PD-L1 antibodies. At the ASCO Genitourinary Cancers Symposium, we heard about the anti–PD-L1 antibody from Genentech/Roche and that there are patients who are having really dramatic responses to it, and I think we will hear more data in the next set of upcoming scientific meetings. Clearly there is evidence that patients with these types of tumors are responding to these immunotherapy agents.

As far as candidate predictive biomarkers of response, are there any leads for anti–PD-1 and anti–PD-L1 antibodies?

There are intensive investigations to look for predictive biomarkers, and I think we have to be really thoughtful in this arena because predictive biomarkers are important; if you can predict which patient will respond, then you can choose the correct patients for treatment and avoid giving the treatment to patients who are not going to respond. So, that helps us from an economic standpoint in that we are not getting extra cost incurred because we are not giving the treatment to everyone, we are picking the right patient.

We saw the importance of predictive biomarkers in genomic medicine; since you can predict, for example, that a patient has a 

 mutation, they will get the drug that targets that mutation. Only those patients with the mutation receive that particular therapy. However, the immune system is very dynamic and cannot fit into the same box as genomic medicine. The immune system changes on a daily basis. The immune response we measure today is not the same immune response we see tomorrow. And that makes it difficult to come up with a predictive biomarker. We want to be careful and not restrict the therapy from patients who could potentially benefit. We want to give patients the chance of the best clinical benefit possible. These therapies to date do not have a predictive biomarker that show that only some patients should get the therapy.

In this interview we discuss predictive biomarkers and response to immune checkpoint inhibitors for urothelial tumors, which include tumors of the bladder, ureters, and the renal pelvis.

Bladder Cancer

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