Locally Advanced RCC/Kidney Cancer; Dr. Chris Wood; Options & Treatment 1/4 Parts

Dr. Christopher Wood, of MD Anderson Cancer Center lectured at an April 2012t KCA patient conference on this critical subject.  It is a technical discussion, highly important for the patient whose kidney cancer is not longer consider “small and curable” by surgery alone.  For greater ease in following this, I have posted this in four segments. My comments  will follow in a separate blogs.  My hope is that the information is meaningful, so that a patient can learn enough to have a discussion with his/her doctor.  Print out the information you have read and give it to the doctor to start that discussion.  Some slides were principally text, so I have recreated some to keep the file size down; anything which was not readily converted to text remains as the best available slide.

Consider saying to your doctor, “Here’s what I have been learning, doctor.  How does that fit into our plan for my treatment?” That tells your doctor know you are willing to learn and to listen, and to take an active role in your treatment decisions.  Unless your doctor deals daily with many kidney cancer patients, he is unlikely to be able to keep up with all the information, ever changing, and ever more complex, about your disease. If the doctor is not willing to listen and learn from the leaders in the field…find another doctor.

Peggy: RCC Patient, Stage IV mRCC 2004; healthy today, thanks to HD IL2

“Outcomes for Patients with Locally Advanced Renal Cell Carcinoma”

http://www.youtube.com/watch?v=Ns7qDbn_0_E&list=UUv0VRYOltlNQJLCyNMN61Nw&index=49&feature=plpp_video

Dr. Wood begins: “My first lecture is “The Management of Locally Advanced Renal Cell Carcinoma”. Slide 1

Stage is the most important predictor of outcome: the more advanced the stage, the greater risk that the tumor has spread, with distant metastases, making the disease incurable.

This is the staging system we use in 2012,  where we stage tumors,  assess regional lymph node involvement and look for evidence of metastatic disease.  People get hung up on their staging, but this allows doctors to communicate about patients in the same language about how advanced one tumor is.  With increasing stage, there is a more locally advanced tumor or metastatic disease.

Let us start with definitions. (Reads slides 2 & 3)

Adjuvant Therapy means some form of therapy– chemo, radiation, vaccine, whatever–after complete surgical tumor resection with the idea to decrease the risk of recurrence of disease.  The benefit is that the patient has already had surgery before getting additional therapy, but the downside is that many of those patients may have been cured by the surgery and they may get treatment they don’t really need.

Neoadjuvant therapy is taking some form of therapy, whether chemotherapy, radiation, vaccine, etc. prior to surgery to the primary tumor in hopes the tumor may decrease in size, and decrease the risk of recurrence.  The benefit is it may allow the tumor to shrink and make surgery easier.  The downside is that the therapy may not be effective and not inhibit metastases, and the primary tumor would not regress, but progress during therapy.

Slide 4

Effective adjuvant or neoadjuvant therapy does not exist for kidney cancer in 2012

Any therapy must be developed in the context of a clinical trial setting, and  including a placebo.  The only way we  make advances is to test what we do now with any advance in the future. And what we now know, as I said, is nothing.Patients have a hard time, with placebo trials. If you participate in such a trial, the treatment you are getting may not be good and the placebo arm, not so bad.

Slide 5  Who should get these therapies?  Why not give them to everyone?  Anyone taking the targeted therapies today knows the toxicity is significant, and you may treat a significant number of people who really don’t need the therapy.  Then if nothing works, why not give it to anyone? Well, we are never going to make advances that way, so it is important that we continue to do research and focus on those who are highest risk for relapse.  Should we give it only to those at a highest risk for recurrence?  The difficulty how do we define risk, how high is high?  So it’s not really clear.

Adjuvant Therapy: 2012

A variety of trials have been performed. Many  patients  have participated. They include radiation, embolization, energy ablation, a variety of different hormonal therapies, immunotherapies with interferon and interleukin 2, all having been used in an adjuvant setting.  There have been a variety of vaccines preparations and we did a Phase III trial of thalidomide trial here. To date, not one of these therapies has shown benefit in the adjuvant setting.  In fact, many of the patients on the treatment arms did worse than those who were not treated.

Slide 7 What about targeted therapies?  That is also the great unknown where  things stand with targeted therapies in the adjuvant setting.

Since 2006 there have been seven new agents against kidney cancer. It’s been a revolution. And to be honest, many  have benefited from that advance.   How do we use these agents in the context of adjuvant therapy?

Slide 8 There is a variety of trials recently completed or in accrual, ongoing. Tthe ARISER Trial used an antibody called G250 against Carbonic Anhydrase IX, and patients were randomized to get  either antibody or placebo. This trial completed accrual many years ago, in fact, and we are still awaiting results which leads me to believe that is probably going to be a negative trial.

But this same agent has recently shown promise for use in PET scans for kidney cancer.  You can use this as an imaging agent. The patient is infused with the antibody and linked to item 125, and it will show up on x ray, and may potentially detect micro metastases not visible on CT scans.  This is actually undergoing FDA approval.

­Slide 10

This is the ASSURE trial we conducted at MD Anderson.  It is a randomized, double-blind phase III trial of Sunitinib vs Sorafenib vs Placebo. Patients underwent surgery, then were treated with these agents for 1 year.  This trial was completed accrual last September (2011) and we are now waiting for the trial to mature to see whether these agents have any benefit in the adjuvant setting.

Slide 11

One thing that we did learn from this trial is that tolerance for the toxicity associated with targeted therapy in the adjuvant setting is not the same as in the metastatic setting. In this trial 41% of patients stopped therapy early, not because disease returned, or because they finished, but because of toxicity.   I think it comes down to an individual assessment of the risks.  If I told you that you have a 20% risk of your cancer coming back, versus your 70% chance of your cancer coming back and you are miserable on this therapy, all of a sudden 20% doesn’t look so bad.

My concern about this, because at the end of the day, if this trial matures and it is negative, will it be negative because the agents did not work, or because the patients could not tolerate the side effects. And too many patients stopped the trial early or had dose reductions.  I’m afraid it is not going to be interpretable.

Slide 12 This the S-TRAC trial, sponsored by Pfizer, recently completed accrual.  It’s randomized between Sunitinib with a placebo for one year. It is estimated results will come out in 2017. That’s the other problem with these trials. Are the agents we are testing now, will they even be relevant in 2017?  No one knows.

Slide 13/12

There has been a real problem in accruing to this trial. In fact, we can’t even keep patients on Sorafenib for three years in treatment, never mind adjuvant setting.


Slide 13

This is a trial going on in the US, sponsored by Glaxo-Smith-Kline. This is called the PROTECT trial.  Patients are randomized to Pazopanib (Votrient) or placebo for one year. This is primarily open to clear cell patients, here at MD Anderson.

SLIDE 15 A

This is the EVEREST trial, sponsored by the SWOG, going on around the US, with patients randomized to one year of Everolimus (Afinitor) or one year of placebo.

You can see that clinical research is actively ongoing to identify if these agents work in the adjuvant setting. But it is going to take more time to understand from these trials before we know if this is applicable in these setting or as with the other agents, if they remain ineffective.

Slide 16

One other concept we are testing at MD Anderson that I will talk about a bit more in the next talk is a neoadjuvant therapy, testing Axitinib in the neoadjuvant settings. Some in the audience have been on this trial, where patients receive Axitinib for three months and then undergo nephrectomy.

I would like to applaud the patients who participated in this trial.  Like to give you an idea how this went the first time we enrolled a patient.  Patient comes in with a tumor, curative with surgery, and we say, “We’d like to give you this agent, we don’t know if it will work.  In fact, your tumor may grow and metastasize while you are getting this agent.  If we took you to surgery tomorrow, we could probably cure you. What do you say?”  It was really amazing. The first patient who enrolled in this trial was very brave.  But since we have been able to show activity with this agent, enrollment has picked up significantly.”

Dr. Christopher Wood ends the first part of this lecture, with the next section about “The Surgical Management of Locally Advanced Renal Cell Carcinoma.”

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