OncologyTube: Okay, we’re here at ASCO GI 2024. We have Dr. Manish Shah, medical doctor, and the director of gastrointestinal oncology program at Weill Cornell Medicine in New York. Thank you so much
Manish Shah, MD: for joining us today. It’s great to be here. Thank you.
OncologyTube: Today, we’ll be discussing first line pembrolizumab plus chemotherapy for advanced esophageal cancer five year outcomes from the Keynote 590 study, a phase three study featured here at ASCO GI 2024.
So Dr. Shaw, could you provide an overview of the five year follow up data from the Keynote
Manish Shah, MD: 590 study? Absolutely. So this was a landmark study. This was an examination of chemotherapy with or without pembrolizumab in esophageal cancer. Um, the study, uh, began several years ago and, um, it was a positive study.
Pembrolizumab does improve survival [00:01:00] and it led to regulatory approval of pembrolizumab. Um, and that was a few years ago. Um, the real update from, uh, this, uh, abstract was the long term survival, five year survival. Um, and what we showed is that there was a sustained benefit of the addition of pembrolizumab to chemotherapy in esophageal cancer, even up to five years.
Um, and to put numbers on this, um, Patients who are randomly assigned to chemotherapy alone, there is a, you know, less than 5 percent chance, maybe 3 percent chance of surviving five years. That’s a really tough disease. Um, but with pembrolizumab, um, depending on, you know, which subset you’re looking at, the survival at five years was between 10 and 15 percent.
So three to five times better than with chemotherapy alone, which is really quite something. It’s still a small number. We need, you know, we have to do work, but It’s, it’s a real step forward, I think. All
OncologyTube: right. So, how did the five year follow [00:02:00] up data from the Keynote 590 study impact your considerations for first line treatment options in patients with advanced esophageal cancer, especially in terms of overall survival and progression free survival?
Manish Shah, MD: Yeah, that’s a great question. So, you know, we’re in an era where patients have more and more options for treatments. Um, and I think these data really highlight that, um, if you’re eligible for immunotherapy with your chemotherapy, you really should consider getting it because there’s a chance that you could survive five years Uh, with really good disease control without progression and I think that’s really remarkable.
I mean we used to think that at five years if patients, you know, didn’t have progression they would be cured as an oncologist We’re really, you know hesitant to say the word cure but to to make it that long Uh with without disease progression with you know, and surviving is really something so I think it highlights the fact that um, this is an option that you should really consider especially considering that the Side effects, [00:03:00] the toxicity of pembrolizumab are really quite minimal.
OncologyTube: Excellent. Uh, can you discuss the durability of the effect efficacy observed with pembrolizumab in combination with chemotherapy over a five year period in comparison to placebo with chemotherapy and how it may influence treatment decisions for these
Manish Shah, MD: patients? Yeah. So the way that the study was designed was that, um, you get chemotherapy, uh, for about six months and then you, you, um, can taper that down or stop it because of cumulative side effects.
Then you would continue pembrolizumab if you’re assigned to that arm for up to two years. So about, um, ten percent of patients on the study actually completed the full two two years of pembrolizumab. Uh, conversely if you were randomized to chemotherapy alone only a handful of patients actually received two years of therapy meaning that their cancers progressed and they had to move on to a different type of treatment.
Um, so, you know, starting, you know, put, you know, out of the [00:04:00] gate starting with immunotherapy with chemotherapy for some patients really was quite amazing. And it was the only treatment that they received. Um, and I think what we’re also learning, um, from this study and other studies is that, um, if you have.
Even if you have metastatic disease, stage 4 cancer, if you have a good result with, um, the initial treatment, you should think about doing additional treatments, radiation or surgery or whatever, to get rid of the disease that you have, uh, because those are the patients that potentially could survive longer.
OncologyTube: Alright, so given the safety findings including treatment related adverse events and their impact on patient outcomes, how would you assess the overall risk benefit profile of first line PEMBRO and chemotherapy in patients with untreated advanced esophageal cancer, especially in the context of long term treatment?
Manish Shah, MD: Yeah, that’s a great question. Uh, we don’t think about that, um, as much, but I think we should. So immunotherapy, [00:05:00] um, generally is really well tolerated. Um, it really functions by activating the patient’s immune system, their own immune system, against the cancer. Um, sometimes, less than 5 to 10 percent of the time, um, it can activate the immune system against the patient’s own body.
So you get it. Colitis or Pneumonitis or it could affect your thyroid or things like that. Um, in the study that I just presented, um, we found that the long term, you know, um, immune adverse events were about 7%. Um, whereas in the chemotherapy arm, the long term immune adverse events where, you know, the similar side effects were about two to 3%.
So it’s, it is more with immunotherapy but it’s marginally more. It’s a, it’s a few percentage points more. So it’s something that we need to monitor and, uh, take care of. Um, the other thing is that we’re much smarter by how to take care of these immune related side effects. Um, and we can, um, you know, if, if it becomes severe, we [00:06:00] can actually, uh, give immunosuppressive therapy to stop the immune system from being so hyperactive.
So we, we have better tools to treat these side effects as well. So I think on balance, if you’re able to manage the side effects better, um, and they’re relatively You know, less common and there’s a potential of long term survival. Um, I think it really, it really makes a lot of sense for this treatment to be considered as a key, you know, first line treatment option for patients with esophageal cancer.
OncologyTube: All right, well this has been Dr. Manash Shah, medical doctor and the director of gastrointestinal oncology program at Weill Cornell Medicine in New York City. Uh, Dr. Shah, thank you
Manish Shah, MD: so much for chatting with us today. Thanks so much, it’s great to be here. Mhm.