ASCO 2019: Right to Try Legislation and Why Clinical Trial Entry Criteria Need to Change
Dr. Shanahan was part of a panel on Right to Try Legislation at the 2019 American Society of Clinical Oncology Annual Meeting. In this podcast, she explains Right to Try and Compassionate Use legislation and why she thinks the real answer is changing the criteria for enrolling in clinical trials.
Listen to the podcast to hear Dr. Shanahan talk about:
why she thinks Right to Try legislation is flawed
how the common criteria for entering a clinical trial exclude a majority of people diagnosed with metastatic disease and how trials can be changed
how she would proceed if her disease progressed and she didn't meet the eligibility criteria for an appropriate clinical trial
Dr. Kelly Shanahan is a metastatic patient advocate and METAvivor board member. She had to give up her OB/GYN practice because of side effects from metastatic breast cancer treatment.
— Last updated on May 5, 2022, 6:35 PM
This content made possible by Lilly Oncology.
This podcast is made possible by the generous support of Lilly Oncology.
Jamie DePolo: Hello, and welcome to the Breastcancer.org podcast. I’m Jamie DePolo, senior editor at Breastcancer.org. We’re on location at the 2019 American Society of Clinical Oncology Annual Meeting in Chicago. My guest is Dr. Kelly Shanahan. Kelly describes herself as a mother, wife, daughter, doctor, and woman living with metastatic breast cancer. Neuropathy from breast cancer treatment forced her to retire from her OB-GYN practice. Kelly now works tirelessly as a metastatic breast cancer advocate.
Kelly was part of an ASCO panel on Right to Try legislation yesterday. Today, we’re going to talk to her about Right to Try through the lens of someone with metastatic disease. Kelly, welcome to the podcast.
Dr. Kelly Shanahan: Thank you very much, Jamie, for inviting me for this opportunity.
Jamie DePolo: So can you talk to us a little bit, just in case someone’s not familiar with you, about your initial breast cancer diagnosis and then your metastatic diagnosis and kind of tell us where you are today?
Dr. Kelly Shanahan: So I’m one of the 25% to 30% that no one ever talks about, the people that start off early stage and become metastatic. I was diagnosed with stage IIB, ER-positive, HER2-negative breast cancer in 2008 on a routine, although not annual, mammogram.
I underwent pretty conventional therapy because of where I live in Lake Tahoe and the fact that I was a mom and solo practitioner in a busy OB-GYN practice. I chose to have a bilateral mastectomy with immediate reconstruction. I had one positive lymph node, which bought me the typical 4 months of chemo with Adriamycin, Cytoxan followed by a taxane. I finished that, and I started on an aromatase inhibitor that caused such severe side effects, arthritis-type side effects, especially in my hand that I will admit that I was a non-compliant patient and I did not complete the full 5-year course.
Five years after my diagnosis, I developed back pain. I had asked my oncologist with early-stage diagnosis, you know, “So do we follow tumor markers, do we do annual scans?” And I was told no, just if you have a symptom report it.
Jamie DePolo: Really? So no real routine follow-up?
Dr. Kelly Shanahan: No routine follow-up, which I was told that finding metastatic disease early doesn’t make a difference in prognosis. Remember, this was 11 years ago. We know things are different now.
So by the time I had a symptom and I had scans, I had metastases in literally every bone in my body. My back pain was from a fractured vertebra, I had an impending fracture in my leg, and I had a rod put down my femur 6 days after diagnosis. Living where I live, there are no full-time oncologists.
I ironically was subletting my office one day a week to an oncologist who came from a different town, and I saw him and he recommended a very, very, very unconventional regimen of combination IV chemo, which I accepted because of the way he presented it, convinced me to do that, and maybe it was the right answer. But I am now on my third line of therapy. I am extremely lucky. I have been no evidence of active disease for 5 of my 5 1/2 years of living with this lovely thing…
Jamie DePolo: That’s amazing.
Dr. Kelly Shanahan: …we call metastatic breast cancer. And maybe it’s because I did that unconventional regimen, but maybe I would’ve done just as well by just being on an aromatase inhibitor. But one of the things I’ve come to learn is because of the number of prior lines of therapy, I may not qualify for future clinical trials, which is why I think that all patients should have access to promising investigational new drugs outside of a trial through mechanisms such as FDA [Food and Drug Administration] Compassionate Use and also the federal Right to Try legislation.
Jamie DePolo: Okay. So just in case anyone’s unfamiliar, can you explain what Right to Try is and how that works?
Dr. Kelly Shanahan: So prior to the passage of a federal law, which was signed last year in 2018, there was a patchwork of states that had Right to Try state laws passed. And basically what that means is it allowed the patient to ask, petition a pharmaceutical company, for delivery of a drug that had not yet gone through the FDA pipeline and had been FDA-approved.
The federal law extended that to every state. So what it means — and I think really it should be called Right to Ask, because there is nothing in this federal legislation nor is there anything in the FDA Compassionate Use program that compels a pharmaceutical company to supply a drug. Both of these programs require that the drug has passed phase I safety trials.
Jamie DePolo: Okay.
Dr. Kelly Shanahan: So it’s been evaluated in humans. It’s shown to be safe. It hasn’t done any efficacy trials, but it also has to still be in the FDA pipeline. It can’t be a drug that someone did a phase I on, showed that it was okay safe, but maybe they’ve already done a phase II and it shows there’s no efficacy and it sucks, and they’ve withdrawn their application.
The drug has to remain in the FDA pipeline. One of the major differences between Right to Try and Compassionate Use, where I think Right to Try potentially could be more useful to people living in communities and being treated by a community oncologist, is Right to Try does not require approval from an institutional review board [IRB]. With the FDA, you have to have IRB approval and for someone in a small community oncology practice, they don’t have an IRB. So I think that potentially could make this available to more patients. For me it’s the idea of patient autonomy. There are other organizations, breast cancer organizations, that came out against Right to Try.
Jamie DePolo: Well, ASCO did.
Dr. Kelly Shanahan: ASCO did, and I think there are good reasons for why they came out against it. There’s no data collection with Right to Try. We’re not learning anything from the success or the failure of whether this drug may work in an individual patient like you do with the FDA, there’s some oversight.
But some of the concerns that were expressed, like patients are going to be taken advantage of, patients are going to be, you know, raped by these companies and they’ll pay anything, they’ll be bankrupted. They’re going to be given drugs that are unproven and unsafe. Well, any patient that enrolls in a clinical trial is trying out a drug that’s unproven. That’s the whole point of a clinical trial. It’s been proven to be safe or at least safe enough, and the same thing applies to Right to Try. And again, I believe let us as patients make the decisions for ourselves, and that’s what Right to Try does.
I don’t think it’s perfect. In fact, Right to Try is not that great. The federal law’s been in existence since early in 2018, and the first two patients to access a drug through Right to Try were in November of 2018 and January of 2019.
Jamie DePolo: So yeah, it took a long time.
Dr. Kelly Shanahan: It took a long time, and I frankly don’t think that a lot of companies are going to make their investigational drug available. But again it’s another avenue. Let us make the decisions for ourselves. In a perfect world, we’d be in clinical trials. Seventy percent of us want to participate in a clinical trial, only — depending on what you read —somewhere between 3% and 8% of us do. And the problem is trials are… the criteria are too restrictive. You have to be, I call it a cancer Olympian to be able to participate.
Jamie DePolo: What do you mean by that?
Dr. Kelly Shanahan: The trialists want the healthiest of those of us dying with cancer because a lot of trials are done in the metastatic setting first. But they want people who have… maybe this is going to be their first line of therapy is the trial drug, maybe their second. If you find a trial that allows two prior lines, you know, God forbid, three or four, five, like many of us out in the real world have already gone through, I mean, consider yourself really lucky. I mean, go buy a lottery ticket!
They also want people that are really healthy. You know, there is something called the ECOG [Eastern Cooperative Oncology Group] Performance Status, where stage 0 is you could basically run a marathon. But a lot of us with disease might be stage II, which is you can do most things, but you’re going to get short of breath walking up the stairs. They don’t want us. But those are the people that are going to be using the drug when that drug is finally approved.
The participants in trials don’t currently reflect the population. They tend to be younger, even though in breast cancer especially it tends to be an older population, although unfortunately we’re seeing a lot of young women, young women and men, with metastatic breast cancer. They do things like exclude men for no good reason.
Jamie DePolo: Right. Right.
Dr. Kelly Shanahan: I was looking at a poster today, and one of the exclusion criteria for this drug for this potential study for an estrogen-receptor-positive metastatic breast cancer patient was it excluded patients with bone-only disease. Well, guess what the most common site of estrogen-receptor-positive metastatic disease is? It’s bone, and many of us are lucky enough to start off bone-only. And when I asked, “Why did you exclude these patients,” the answer was, “Well, we’re requiring a biopsy.” And I had a friend where I live who had a bone biopsy done 2 weeks ago.
So there’s these crazy exclusionary criteria that make trials more difficult, but that’s what we as patients want. The perfect world, we wouldn’t have this discussion about Right to Try or Compassionate Use because the people that wanted to enroll in a trial would be able to enroll in a trial, and they’d be able to enroll in a trial close to where they live and work.
Jamie DePolo: Right. Well, and I know oftentimes trials exclude people with brain mets, too, which has been a big issue.
Dr. Kelly Shanahan: That has been an issue. And that shouldn’t be happening anymore, because last year, maybe a year and a half ago by now, the FDA published a white paper that said you shouldn’t exclude patients with stable brain metastases, you shouldn’t exclude people just because they have HIV, you shouldn’t exclude people just because they may have had another cancer 20 years ago that is never going to cause a problem.
So the FDA is really doing a lot of excellent work. You have to transmit that information out to the general population. And the FDA is part of a working group including ASCO, Friends of Cancer Research, AACR on broadening eligibility requirement. Things like why do you have to have a 28-day washout period before you start a study drug? Nobody in the real world… it’s like, “Oh, you have progression, let’s stop your drugs for a month…”
Jamie DePolo: Let’s wait a month.
Dr. Kelly Shanahan: …before we start the next thing.
Jamie DePolo: Right.
Dr. Kelly Shanahan: Looking at bringing trials to the patients, decentralizing trials, looking at prior lines of therapy, why are we blanket… let’s include more people that reflect the real world. So there’s progress. You know, those of us with metastatic disease, especially, don’t think the progress is fast enough.
But this whole thing with the FDA and brain mets and HIV, that happened really, really fast. So, you know, there’s definite hope, and advocates like us, by continuing to talk about this, by developing relationships with people in industry, in the regulatory agencies, in academia, we can really move that dial.
Jamie DePolo: Okay. So how did the session go yesterday given that it was here at ASCO, and ASCO was opposed to the Right to Try legislation. Was it lively?
Dr. Kelly Shanahan: This was really interesting. It was what’s called a ticketed session, which means the people that attended had to pay extra money above the somewhat high registration fee. So I was telling all my advocate friends, “Nobody’s going to be there, you’ll be able to get in.” I walk up to the session, and one of the ASCO people there was like, “It’s sold out.” And my response was, “Holy shit.” Not everyone that buys a ticket actually attends, but there were a good number of people there.
The oncologist Todd Bauer that I was on the panel with, you know, I think initially thought he was going to be taking the anti-Right to Try, pro-going-through-the-FDA approach, and I was going to take the opposite. But one of the things I led with was basically what I said now, Right to Try sucks, Compassionate Use sucks a bit less. And what we want as patients is clinical trials. But I think patients should have this option because I hate those paternalistic arguments against it.
We left a lot of time for discussion. We could’ve gone over our allotted time. There were a ton of questions and comments from the audience, a lot of it about how can we improve the clinical trial process, how we can think outside the box, do things differently. There was a pediatric oncologist there, and I really appreciate his comments, because in pediatrics, like 60% of pediatric cancer patients participate in a clinical trial. And he was kind of taking the medical oncologists treating adults to task for why… yes, it is a larger population, therefore, it’s more money. But, you know, if we can do this in pediatrics, you can do this in adult medicine.
Jamie DePolo: Is that because of the way the trials are designed that there’s such a high rate of pediatric patients in clinical trials?
Dr. Kelly Shanahan: I think there’s a couple of reasons. There aren’t as many pediatric cancer patients. A lot of them are treated, you know… General oncologists don’t treat pediatric patients. They usually refer to a pediatric oncologist who is at a major center. You know, I live at Lake Tahoe. But Reno, Nevada has a pediatric oncologist who happened to have grown up in South Lake Tahoe — I know her dad, her dad was an OB-GYN. And she is now there, but she also has an appointment with I think Children’s Hospital in Oakland. So the pediatric patients now in northern Nevada, northern California can get treated more locally, unless — there are certain things where you really need to go… I’m a huge proponent of bringing trials to the patients, but I would never in a million years suggest that, I don’t know, a CAR T trial should be done in the community. Absolutely not. There’s certain trials, it’s just not appropriate.
The other thing that’s really interesting is this high percentage of pediatric patients who do trials, their survival rate is through the roof. It used to be you were diagnosed as a little kid with a pediatric leukemia or a brain cancer, you died. And their survival rate in some of these cancers is 85% now, and that’s because there were trials and they now can deliver. And I think we can improve the survival rate for adult cancers if we have more people more reflective of the real population that are allowed to participate in trials.
Jamie DePolo: Okay. From your viewpoint, I know you said Right to Try isn’t super great, but are there any inherent risks, say, if somebody was thinking about access to the drug that way?
Dr. Kelly Shanahan: I think patients need to be informed. I think if you are requesting a drug through the Right to Try process, and your doctor doesn’t sit down with you for at least an hour going over the pros and cons, that person is committing a disservice to you.
These are drugs that have not yet been studied in your particular situation. They have some promise. There may be promising animal trials. Yes, they have safety data. Some other human being has tried this drug, and they have some idea about dosing because they’ve gone through the phase I and a lot of them have gone through phase I, phase IB, something that in the old days might have even been considered a phase II trial. But we don’t know what’s really going to happen. And so there are definite risks that your cancer could progress, that you could have intolerable side effects. And so I do think that patients need to be informed of that.
On the other hand, there is potential. This could be the drug that works for you, but you don’t have 2–3 years to wait for the clinical trial to be completed. And I think if patients are aware of that and that patient says, “You know what, I will take that risk,” then I think they should be allowed to go for it.
I wish there was data collection. But I think as a patient, you can say to your physician, “I know you don’t have to do anything with this, but I want you to collect the data. Just send an email to the manufacturer, give them the information.” There’s nothing that says you can’t collect data. It just says you don’t have to, right?
Jamie DePolo: Well, and you would think, or at least I would think, that the companies, the pharma companies, would want that data.
Dr. Kelly Shanahan: You would think they would want that data unless it’s negative data.
Jamie DePolo: Well, I suppose that that’s true.
Dr. Kelly Shanahan: But again, it’s not going to get reported to the FDA. It’s not going to make a hill-of-beans difference in whether that drug gets approved or not approved. There is the potential from the industry standpoint, and I think one of the reasons why it is so hard to get industry to agree to give a patient a drug… there’s two reasons.
Under Right to Try, they can charge the patient whatever the heck they want. They could charge the patient $500,000. But if that gets out in the media, that can reflect negatively. If they give the patient a drug and the patient dies or has horrible side effects and that gets out, that could affect that company’s bottom line. Which is why I think Right to Try really isn’t going to make a difference, because I don’t think many companies are going to provide the drug to the patient.
Of these two patients that I mention, one of the patients was treated at — and I’ve spoken to the principal investigator, I’ve spoken to the doctor who gave the patient the drug, she is the PI on a trial using this treatment. It’s a cancer vaccine treatment for glioblastoma. This patient was her patient who did not qualify for the trial, so it was super easy for her to obtain the investigational agent. She told the patient about Right to Try and Compassionate Use. She’s gotten other patients’ drugs through the FDA Compassionate Use program, but the patient and his family chose to do the Right to Try route mainly because it’s faster, even though the FDA will turn around their things in about 24 or 48 hours. But because she really didn’t have to petition a company to get a drug, she just had to talk to the people involved going, “Hey, I’m the PI on your trial and I want one dose for my patient,” she was able to do that. And what she told me was that the family was very grateful for the opportunity to try this.
The second patient is one of the patients who this law is actually named after, Matt Bellina, ALS patient. And he received his treatment through Right to Try just in January of this year. But the company has already said — and they said before they gave him this drug — that they will not provide any other patients with this treatment because it’s too expensive and they just can’t do it.
Jamie DePolo: So ultimately it does come down to the company deciding whether somebody gets the drug or not?
Dr. Kelly Shanahan: It is absolutely up to the company. That’s the first step in Right to Try. The first step in the FDA process is you have to have a letter from whoever has this investigational new drug stating “I will provide this drug for this patient.”
Jamie DePolo: Okay. And you mentioned you talked to the two patients. Are there…
Dr. Kelly Shanahan: Well, I talked to the…
Jamie DePolo: The PI, I’m sorry.
Dr. Kelly Shanahan: …doctor of the glioblastoma patient.
Jamie DePolo: Right. So there are two that you know of. Are there any others, or is it really just the two that have tried?
Dr. Kelly Shanahan: That is all that Dr. Bauer and I, who did our talk together, that the two of us could find.
Jamie DePolo: Really? Okay.
Dr. Kelly Shanahan: And a couple years ago when I was advocating for Right to Try, when the law was first introduced and didn’t get through Congress, I looked into this. I couldn’t find, in any of the states that already had Right to Try legislations, a single documented case of a patient receiving a drug through Right to Try in the states that already had existing legislation. And another downside to Right to Try is in some of the states that had state laws — and federal law did not address this, so the state law would still take precedent — insurance companies in some states may decline to pay for hospice care as a result of the patient participating in Right to Try. A couple states, the insurance companies can decline to pay for anything if a patient avails himself of Right to Try. And the federal law did not address that.
Jamie DePolo: So the idea being that if you’re taking this investigational drug, the insurance company says, “We don’t know what caused where you are now so we’re not paying for anything else.”
Dr. Kelly Shanahan: Right. You take this investigational new drug that you know that neutropenia low white count is one of the side effects, and you get an infection and you’re in the hospital and you’re in the ICU? In some states your insurance company can go, “Yeah, well, we’re not paying for that.”
Jamie DePolo: Wow. That’s a huge downside.
Dr. Kelly Shanahan: Right. Right. And that’s where the patients need to be informed. If they’re in a state that has had Right to Try legislation, that they need to know what their state is. And again, federal doesn’t address it, so if they live in a state that didn’t previously have a Right to Try law, I think that’s a really gray area about what would happen.
Jamie DePolo: So if somebody did want to try, they’ve exhausted treatment options, they’re looking at Right to Try. Are there resources that you would suggest they look at first before they get into this?
Dr. Kelly Shanahan: You know, I don’t think there’s a lot of central information. I think the Goldwater Institute, fairly Libertarian institute, was a proponent of Right to Try, and there may be some stuff on their website about it.
The first thing is, you’ve got to find the drug company to do it. Most doctors are not going to take the time or they don’t have the resources to look at this for you. So most of the time it’s incumbent upon the patient to say, “I follow the literature, there have been some interesting animal trials, I see there’s a phase I about this drug I’m interested in. I don’t qualify for a trial.” And then the patient often has to initiate contacting the company to see if they can get it. Sometimes they can get their oncologist to do that. But as someone who lives in a place not near a research center that — my first oncologist and most oncologists in our area, they don’t have nurse navigators. They don’t have oncology social workers. They don’t have people that can do that, even know what to do. So unfortunately a lot of this is incumbent upon the patient. Just like, frankly, it is with finding clinical trials.
Jamie DePolo: A lot of things. So I’m curious, to wrap up, my last question. If your situation were different and you needed to find a new treatment, would you go through Right to Try or Compassionate Use? How would you proceed?
Dr. Kelly Shanahan: Yeah. If I… When I progress — because at some point I will progress. When I progress, if there are no trials for which I’m eligible, my first route after looking for a trial would be to go through the FDA process. Because even if I croak and die, maybe some of that data will help someone else. But if that were not an option, I would absolutely avail myself of Right to Try. Again, my body, my decision, as it is with a whole lot of other things.
Jamie DePolo: Right. Right. Kelly, thank you so much. I really appreciate your insights.
Dr. Kelly Shanahan: Thank you, Jamie.