Avoiding Chemo in Breast Cancer; Psychedelic Medication for Depression

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of Texas Tech Health El Paso, look at the top medical stories of the week.
This week’s topics include treatment of Achilles tendinitis, avoiding chemo in some types of breast cancer, imaging and cardiac stent placement, and a psychedelic medication in depression.
Program notes:
0:45 Imaging for cardiac stent placement
1:45 12-month target vessel failure
2:38 Treatment-resistant depression and psychedelic medicine
3:38 Three dosages and psychological support
4:38 Adverse events same among all groups
5:38 Will it last longer than 60 days?
6:36 Need to compare head to head
7:00 One in 13 people have Achilles tendinopathy
8:00 Initial improvement with steroids then rapid decline
9:00 People must be patient
9:10 HER2-positive early breast cancer giving chemo a miss
10:10 Utilizing PET imaging
11:10 A third responded just to antibodies
12:47 End
Transcript:
Elizabeth: Can we avoid chemotherapy in some women with HER2-positive breast cancer?
Rick: Are injections helpful for people with Achilles tendon problems?
Elizabeth: Can we use a psychedelic medication to help treatment-resistant depression?
Rick: And using imaging to guide stent placement in people with coronary artery disease.
Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.
Rick: And I’m Rick Lange, president of Texas Tech Health El Paso.
Elizabeth: Rick, how about if we turn right to the New England Journal of Medicine? This study appears to me to be having some rather large implications for clinical practice.
Rick: This is for people that are going to have a percutaneous coronary intervention because they have coronary artery disease. If you do additional imaging during the procedure, you actually get a better result. That imaging is usually intravascular ultrasound. Use of intravascular imaging is associated with a lower risk of adverse clinical events that require an additional procedure. You don’t really have all the data until you’re actually in the middle of the procedure.

Well, a lot of people now are getting the coronary CT. It can provide a non-invasive assessment of the coronary artery disease. Since that’s done before the procedure, can we use that information to guide therapy? Will it be as useful as using intravascular ultrasound?
So this was an international randomized non-inferiority trial; 1,100 patients that had had coronary CT and they knew they needed to have a procedure done. Half of them were randomized to just using that information to guide stenting. And the other half, in addition, had intravascular ultrasound. And they assessed at 12 months what the rate of target vessel failure was. Those in the CTA group, about 4.1% had target vessel failure. In the intravascular ultrasound, about 4.6%. The CT was non-inferior to the intravascular ultrasound.
Elizabeth: And a lot easier to do, sounds like, in providing this information a priori versus having it concomitant with the procedure.
Rick: It is, Elizabeth. It requires several things. You have the expertise and the equipment to do this and do it well. Number two is, remember, it exposes the people to radiation. Now, what the study didn’t do was it didn’t do a cost analysis.
Elizabeth: That, of course, was going to be exactly my next question. And it just seems to me, and I could be wrong on this, but, gosh, CT is just so routine and so quick that I suspect it’s less expensive. But I don’t know that.
Rick: Yeah. And the other thing I should mention, Elizabeth, this was done at elective procedures.
Elizabeth: OK. Let’s turn from here to JAMA, this issue of treatment-resistant depression, a single intranasal administration of the psychedelic mebufotenin for treatment-resistant depression.
This medicine, I should note, is actually a synthetic modification of this toad-derived venom that we’ve known for a long time has actually had these properties. In this case, they looked at this in participants who were 18 to 75 years of age with moderate to severe major depressive disorder that had been nonresponsive to previous attempts, two to five of them, to treat it with current antidepressant medicines. They were looking at two different dosages of this medicine, as I mentioned, administered intranasally, 8 mg and 12 mg. And their comparator was a 0.3 mg administration alongside with psychological support.
Their primary endpoint was a total score change in the Montgomery-Åsberg Depression Rating Scale from baseline to day 29. And then they had a number of secondary endpoints. They also note that their discharge readiness in comparison with other psychedelic medications, like psilocybin for example, was assessed starting 90 minutes after their dosing.
Basically, what they found, it was a little bit curious. This medicine did seem to have an impact. They called it durable. Their day 29 response rates were 35%, 34%, and 12% with regard to 8 mg, 12 mg, and the comparator 0.3 mg dose. Their remission rates were 26%, 18%, and 8% in that same dosing regimen. It’s a little curious, isn’t it? Because the 12 appears to have not quite as good results as the 8 mg dose. They also did note that there were adverse events, but these were more or less the same among all of the doses. The editorialist opines that in comparison to what we already know about things like ketamine and psilocybin, maybe this is something that might add to the armamentarium.
Rick: These individuals, to test the effect of the drug, had to be off their antidepressants. These are people that already have refractory depression. They take them off their antidepressants and they only treat them with this, and then they follow them over the course of 60 days. The fact that a third had some response and a fourth had complete remission, for somebody that has refractory depression and on no other antidepressants, they may actually not be bad results.
Once you treat people with a psychedelic, whether it be this or psilocybin or LSD, you have to observe them until the psychedelic effects wear off. With the other drugs, it’s 4 to 12 hours to have to be sitting around waiting. With this particular medication, most people go home in 2 hours. With regard to durability, it lasted for at least 60 days, a single dose. Pretty darn good.
Will it last longer than 60 days? What is the best dose strategy? What if you combine it with other antidepressants? And the last thing I would want to say, Elizabeth, is the people that were excluded from this study were people that have suicidal ideation because there’s concern that the psychedelic drugs in individuals with depression and suicidal ideation may actually make those worse.
Elizabeth: The editorialist, of course, also points out the suicidality as an issue, as an exclusion criterion in this trial. So those people clearly need to be examined and studied carefully. The editorialist notes that the average patient became only about a third better. Remission rates were below those typically seen with ketamine and ECT . So since those things exist already, maybe it’s important to look really carefully at the practicality of another treatment strategy here.
Rick: Without direct head-to-head comparisons, patients could be different. We would actually need to compare them head to head. The other therapies you mentioned require some expertise and some equipment sometimes. If you could pop someone into your office, give them an intranasal application of a drug that could be effective, even if only in a quarter of individuals, and people would be gone in 2 hours, that’s at least another tool in our armamentarium of treating major depression.
Elizabeth: Let’s turn to The BMJ.
Rick: I was unaware that as many as one in 13 individuals have Achilles tendinopathy sometimes. Although exercise treatment is oftentimes recommended, about half the individuals do not get better and almost half these people end up getting additional treatments such as injections. They’re putting 50 mL of saline between the Achilles tendon and what’s called Kager’s fat pad.
These injections sometimes have just saline, sometimes they have steroids, and sometimes they have a local anesthetic. And the thought is that there’s a mechanical or ischemic disruption of the pain signaling and the steroid has anti-inflammatory effects. Is it really effective? Nobody has ever tested that before.
So 192 adults with Achilles tendinopathy received a sham small-dose injection, the high-volume injection with steroids, or a high-volume injection without steroids. And then they followed them about a year. There were no clear differences between the sham and the high-volume injections, either with or without steroids. It looked like there was an initial improvement in the people that got injections with steroids, but then there was a rapid decline.
However, when they looked at cost-effectiveness, it looked like the high-dose injection with corticosteroids was cost-effective. I kind of scratched my head and said, gosh, if there’s no difference, how could that be more cost-effective? Well, during that initial 12 weeks where it looked like it was a little bit better, that’s when people were able to return to work earlier. Even though at the end there was no difference, the fact that they were able to return to work a little bit earlier made it a little bit more cost-effective.
Elizabeth: Sounding like it’s back to the drawing board for folks with this condition. I’m wondering, does it talk about the natural history of it? How long does it take to resolve in most people in the absence of treatment?
Rick: Really interesting, because they follow these individuals over the course of about a year. Most of the improvement occurred, even in those that had sham, somewhere between 3 and 6 months. It’s a long time. The primary treatment is exercise and anti-inflammatory medications. Those take 3 to 6 months to work, so people have to be patient.
Elizabeth: Let’s turn to Nature Medicine and let’s look at this idea that, gosh, there are some women who might be able to forego chemotherapy in their HER2-positive early breast cancer. This is a trial that’s been ongoing for a while and this is looking at the 5-year outcomes. The study initiated as a noncomparative phase II trial evaluating PET-guided pathological complete response -adapted adaptation strategy to omit chemotherapy in women with HER2-positive early breast cancer. I say early, that was stages I through IIIA, and the breast cancer was operable. They were randomized to receive chemotherapy plus trastuzumab and pertuzumab , or some of them actually ended up getting early chemotherapy, but just a couple rounds of it, and then endocrine therapy.
In the second group, their treatment was adapted according to their FDG-PET response after 2 cycles of chemotherapy and pCR. They previously reported that this de-escalation revealed a 3-year invasive disease-free survival of 94.3%. Here, they’re looking at 5-year results using circulating tumor DNA findings.
After their median follow-up of 5.6 years, that number was almost 90%, 89.5% in that group who were randomized to have their circulating tumor DNA assessed along with the FDG-PET results. They only showed in that group one distant recurrence. What they’re suggesting is that this might be a really important strategy for being able to look at women who might be able to forego that chemotherapy.
Rick: Standard therapy is you give chemotherapy with , and you also combine these HER2 antibodies, the two that you mentioned. OK. Maybe we can forego the chemotherapy if, in fact, people would just respond to the HER2 antibodies. That’s what they showed. And about a third of those patients did respond just to the antibodies and it saved them the toxic side effects of chemotherapy. This is pretty amazing. Anytime we can minimize the toxicity, get a terrific result, that’s great news.
Elizabeth: They do note that this notion of circulating tumor DNA at baseline or during treatment, when they were able to find out, was associated with inferior disease-free survival. What this suggests to me is that looking for the tumor’s DNA in the blood has to really be employed as a clinical marker for both “this might be a strategy that’s going to work for you” as well as “what’s going on on an ongoing basis.”
Rick: Yeah. And so, Elizabeth, you’re right. They use two different techniques. One is imaging. The other used serum biomarkers. If your imaging looked like the tumor had resolved and there were no biomarkers, those were the best outcomes.
Elizabeth: I’m going to go out on a limb here and prognosticate that at some point, I think, that circulating tumor DNA will supplant imaging because, as we’re well aware, frequently imaging misses a lot of metastasis in particular that can be in certain spots in the body where it’s difficult to discern.
Rick: And I would suggest that both will be helpful.
Elizabeth: I think both for a while, and I’m guessing it will supplant. We’ll see what happens.
On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.