Hi everybody, my name is Luis Raez, I’m the Chief Scientific Officer and Medical Director at Memorial Cancer Institute in Miami, Florida. We are a part of the healthcare system here in South Florida. It’s my pleasure to collaborate again with ecancer one more time to discuss today, basically in less than ten minutes, what are the key lessons that we are going to get from ASCO 2023, that happened in Chicago recently, regarding lung cancer. It’s very exciting for us, as lung cancer doctors, there are always a lot of developments but we’re going to talk briefly about only four because of the time.
The most important one, as everybody knows is the update of the study called ADAURA. This was a very important study actually presented three years ago in ASCO. Basically, patients who have stage 1b, stage 2 and stage 3 go for surgery after a diagnosis of lung cancer. We documented three years ago that these patients can benefit from adjuvant therapy with osimertinib after surgery for three years based on the data presented in disease free survival. So in the last three years that’s what we’ve been doing – the standard of care after surgery, if the patient has an EGFR mutation, we are giving osimertinib. But that approval was not strong enough because there were a lot of people that don’t agree. Remember, a lot of times, a lot of patients after surgery are already cured and the controversy was what’s the purpose of giving treatment if they are already cured? Of course, we don’t know who is cured or not because we don’t have a molecular stand-in. But because the evidence was based on only disease free survival it was a little controversial.
However, as I said, we are still doing that because we give the patients the benefit of the drug and the protection. But ASCO was very important this year because the data for overall survival was presented. So that’s why this is the most important answer for lung cancer from ASCO, it was given in the plenary session, presented by Dr Herbst. It basically shows that there is a 50%, exactly 51%, improvement in survival if we use osimertinib after surgery for stage 1b, 2 and 3 non-small cell lung cancer compared with if we don’t do anything other than the conditional chemo after surgery. So that is why it is very important to embrace this concept. If there were doubts before I think there should not be now. If you see the presentation online the survival curves are totally separated, there is no chance they would merge any time soon. This is something that is going to benefit the patients, a 50% improvement in survival, based on the hazard ratio, is a lot. But we know that this is the reality of lung cancer, patients after surgery, most of them are not necessarily cured unless they have very, very early stage. Tumours are going to recur and we need to protect the patients and we have already tried for more than twenty years. Chemotherapy only protects 5% of patients. So that’s why this is very exciting for us – we have a novel therapy. Of course this is limited to EGFR patients only, maybe less than 15% of patients in this country yet, but we are also waiting for data with other genetic alterations providing them with targeted therapy after surgery.
What is the future for this is very interesting because, first of all, remember that the approval is for stage 1b, 2 and 3, so that’s why you will see soon there is another study called ADAURA-2 where they are giving osimertinib for patients with stage 1a. We will look to see hopefully that they benefit from this intervention, decreasing the chance of recurrence and improving the survival.
The other question that we have is, remembering the original ADAURA presented three years ago, we decided to give only three years of osimertinib after surgery. But if you compare with breast cancer and other cancers, sometimes in breast cancer you use five years of therapy after surgery. So there is another ADAURA study comparing three years versus five years and that’s the other one that is very interesting for us because we see, as I said before, the separation of the curves in the survival looks like the osimertinib not only benefits the patients for three years but maybe benefits for more. So it will be very, very interesting to see if the benefit can extend.
Finally, we are doing now immunotherapy before surgery and after surgery so the question is why you cannot give maybe osimertinib before surgery or after surgery. We already have data providing osimertinib before surgery, presented in other meetings, but the most exciting study that is ongoing, a new ADAURA, basically providing osimertinib before surgery is going to show an improvement in survival or not.
So more to come in the field of osimertinib. As I said, this was the most important key presentation that we had in the study.
Now, briefly, I want to talk about another presentation. Regarding immunotherapy, there is a very important study called KEYNOTE-671 with pembrolizumab. Remember, all the KEYNOTE studies are pembrolizumab. So it’s standard of care today to give also immunotherapy after surgery, adjuvant. It’s standard of care today in stage 3 if you want immunotherapy before surgery, neoadjuvant, based on studies that have been presented in the last two years. But the question was is there any benefit to give the patients both – neoadjuvant immunotherapy, surgery and complete one year of adjuvant. That is the question that is important that the study KEYNOTE-671 answered and it was presented at ASCO.
Basically, the patients who receive neoadjuvant chemoimmunotherapy, they went for surgery and then they received the adjuvant therapy with immunotherapy with pembrolizumab. The conclusion is that the study shows that there is a 27% improvement in survival. 27% improvement in survival if you use this intervention to give not only neoadjuvant chemoimmunotherapy before surgery but also continue after surgery to decrease the chances of recurrence.
The event free survival was also positive, the benefit was more than 40% and you can imagine that the complete pathological response, meaning that the tumour is gone, is significant compared with the patients that don’t have this immunotherapy before and after surgery. So that is why it is very interesting that we know now that it is standard of care for patients that are going to have surgery to give the immunotherapy before and after surgery.
Another important abstract is another KEYNOTE, it’s the 789. 789 is a very important presentation that I suggest you review. Because we know for years, this is for patients that have EGFR and these patients with EGFR you will know that in stage 4 we give them osimertinib. Unfortunately, the progression free survival is only 18 months and after 18 months the osimertinib doesn’t work any more and fails the patient. So after that the standard, years ago, was giving immunotherapy because immunotherapy used to be second line. But then we discovered that immunotherapy doesn’t work for these EGFR patients that have failed already the TKI, the tyrosine kinase inhibitor; immunotherapy doesn’t work. Finally in the last three or four years we started to do chemoimmunotherapy because chemoimmunotherapy is the standard of care.
Now if we have a new patient with stage 4 lung cancer you test for genetic aberrations, if there is a genetic aberration you give an oral agent, a tyrosine kinase inhibitor. But if there is no genetic alteration pretty much everybody gets chemoimmunotherapy. The same thing, in the last three or four years all of these patients that are failing EGFR therapy, some of us used to give chemoimmunotherapy because we thought it was the strongest treatment available. Some of us give only chemotherapy alone because we already think that immunotherapy doesn’t do anything.
Finally, this is the answer, the first randomised study that proves that after the patients are having EGFR therapy they were randomised to chemoimmunotherapy versus chemotherapy alone. Chemoimmunotherapy versus chemotherapy alone. You know the results: the progression free survival and the overall survival are not statistically significant. So the numbers are giving chemoimmunotherapy is you have a better response, a little bit better survival, a better progression free survival. The differences, according to the statisticians, are not significant. For that reason, this study settles the debate that we had had for three or four years that after you fail EGFR therapy with osimertinib or whatever, or other agents we are using, we should give the patients only chemotherapy. There is no need to give chemoimmunotherapy to increase the scores and increase toxicity. We still have the option that we use chemo plus an antiangiogenic agent as we used to do before. If you remember standard of care ten years ago when there was no immunotherapy was to give chemo plus antiangiogenic agent because that increased the survival of the patients for some months.
Finally, I want to make a comment about the last presentation because it’s very novel. It’s about the Tumour Treating Fields. As you hear, Tumour Treating Fields is a technology that is approved for the use of glioblastomas in the brain where the patient gets electric fields in the skull and the electric fields help to destroy the mitosis and they have an antimitotic effect. The idea is these electric fields help the chemotherapy to kill the tumour. So this is the first time for us in lung cancer that in this ASCO Dr Ticiana Leal from Edinburgh University presented the data of the randomised phase III study for patients that are in second line. Half of the patients have the Tumour Treating Fields on top of their chemo and the other half of the patients have only the chemo. It was very interesting to find that there is a 26% improvement in survival when the patients use the treatment Tumour Treating Fields compared with the patients that don’t use anything, only chemo or immunotherapy. Even the benefit for immunotherapy was even greater than that, it was close to 40%.
So that’s why it is very interesting - we never heard about this technology before. Only for glioblastoma. Now we have the first randomised phase III study that is positive. Very, very interesting and I know that this company is now doing tests in frontline and other indications. But this can add to the armamentarium that we have. This is non-invasive: Tumour Treating Fields are patches that you put on the chest of the patient and on the back and the patient can wear inside clothes. But they have to be used for a whole day, close to 20 hours a day. It’s something very, very interesting and hopefully we will increase our chances to fight against cancer.
So thank you very much for your attention, will be until next time.