ESMO 2022: Lung roundup

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Published: 4 Oct 2022
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Dr Luis Raez - Memorial Cancer Institute, Miami, USA

Dr Luis Raez speaks to ecancer about updates in lung cancer from ESMO 2022. He talks about the following studies in this roundup:

Mechanism of Action and an Actionable Inflammatory Axis for Air Pollution Induced Non-Small Cell Lung Cancer: Towards Molecular Cancer Prevention
Osimertinib as adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) stage IB-IIIA non-small cell lung cancer (NSCLC): Updated results from ADAURA
IPSOS: Results from a phase III study of first-line (1L) atezolizumab (atezo) vs single-agent chemotherapy (chemo) in patients (pts) with NSCLC not eligible for a platinum-containing regimen
Sotorasib versus docetaxel for previously treated non-small cell lung cancer with KRAS G12C mutation: CodeBreaK 200 phase III study



Hi everybody, my name is Luis Raez, I’m a medical oncologist and the cancer centre director of Memorial Cancer Institute here in south Florida, United States. It’s a pleasure to be with you talking in the next minutes about the best of lung cancer in ESMO 2022. We have had very interesting presentations, probably the one that was more noticed in lung cancer was the presentation of the Francis Crick Institute, Dr Charlie Swanton talked about air pollution. That was very funny because everybody is waiting to hear about some new drug. But it’s interesting, we’ve been trying to prove that air pollution causes lung cancer for a long time. It’s obvious that smoking causes lung cancer and now we do CT screening for lung cancer but two years ago there was a first study called TALENT from Taiwan that was the first time that we did lung cancer screening in people that are non-smokers and there were people exposed to air pollution, people exposed to toxins when we cook, people exposed to [inaudible] when they cook, and contaminants and also hereditary factors. That study, if you remember, was positive – 2.6% of the people enrolled in that study, TALENT, despite the fact they never smoked were found to have lung cancer. So that’s why air pollution is very important. 

Basically what they did at ESMO now, they said exposure to 2.5 microns particularly mattered, we call them PM2.5. The exposure can increase your risk of non-small cell lung cancer in people that don’t smoke and it’s going to have EGFR mutations. They said, ‘But how can they do that?’ Well, that is air pollution and basically the explanation that Dr Swanton gave is they cause an inflammatory response and the inflammatory response with the release of interleukin-1β can cause cancer in this non-smoking population. 

This is very interesting, it’s very challenging, but the importance of that is that this amount of air pollution is not noticeable – more than half of the air already has this amount of air pollution, especially in large countries in Asia. So this is something that we have to take very seriously because if we corroborate this with other studies we are going to have to do healthcare policies because we are going to know that the contamination in our cities is really causing lung cancer on top of tobacco, radon and all of the other things that we knew. 

That was the first one. The other one that I think is important to comment was the presentation about ADAURA. If you remember, two or three years ago we presented ADAURA that increased the disease free survival in patients that had surgery and they were stage 1b, 2 and 3. So at that time we got an FDA approval, historical approval so that patients after surgery are going to have not only chemo, four cycles, standard of care, but on top of that now they’re going to have three years of osimertinib. So in this ESMO there was the updated extra two years of data that showed that it was a 73% reduction in the risk of recurrence or death with osimertinib in the overall population.

This is very important because that includes stage 1b. Remember, stage 1b, small tumours more than 4cm. Because the other thing that we use for adjuvant is immunotherapy. We use now immunotherapy, it’s FDA approved, but immunotherapy only works for stage 2 and stage 3; we still don’t have immunotherapy for 1b approval. That is why osimertinib covers 1b, covers 2 and 3. That is also regardless of the prior adjuvant chemotherapy that the patient had or not because sometimes that’s another controversy – ‘We should do chemo, we should not do chemo if we are going to give osimertinib.’ Our standard of care is surgery, chemo and then osimertinib unless there is a reason why the patient cannot have osimertinib. But that’s why this was a very important presentation. 

The other one is that IPSOS. Why is this study important for us? Because normally the standard of care when you use in lung cancer metastatic disease chemo-immuno or immuno alone, these are the two options. We only enrol people with PS0 or 1 so we don’t enrol people with performance status 2 or 3. So, for all of these poor patients, honestly, there is no standard of care. So in this study, IPSOS, they enrolled people with performance status 2 and, of course, these patients, the reason why we don’t give any carboplatin is because they cannot tolerate it or it’s too toxic. So they only give a single agent chemotherapy other than carboplatin. They compared atezolizumab versus single agent chemotherapy other than carboplatin. It was very interesting because the patients seemed to benefit from the atezolizumab, they had better response rates and they had better disease free survival. You’re now talking about a population that before the standard of care was doing nothing. It was necessary to match against chemo because somebody always says, ‘Okay, instead of giving you nothing I’ll give you a little bit of gemcitabine, a little bit of vinorelbine, they are not very toxic,’ outside guidelines. So that’s why it was interesting to know that immunotherapy is an option for them. It’s a single agent administration. Also it’s important because it was for older adults – most of the clinical trials that we do, despite the fact that for lung cancer the median age is 72, in most of our clinical trials we only enrol people below 65. So it’s important to know that for senior populations we give this option to have atezolizumab single agent. That’s something for you to consider that can be an option for our patients.

The other interesting presentation was CodeBreaK 200. If you remember, we have sotorasib approved for KRASG12C patients. Because of approval it’s now standard of care. But, as you know, most of the drugs now are not approved with overall survival, the drugs are approved with disease free survival or progression free survival or event free survival. These approvals are conditional that we get the full approval after. So it was a little bit surprising because we got approval with the CodeBreaK 100 and now we were expecting that with the CodeBreaK 200 we are going to have survival data showing that sotorasib is better.  So it was a little bit of a surprise that the overall survival for sotorasib is not positive. I guess the statisticians say that maybe the study was not really being prepared to have survival data. I guess we have to back up and say, ‘Okay, there’s nothing wrong with that, it was not prepared for survival. No problem.’ The answer to the basic survival data with sotorasib is going to continue to be limited to disease free survival and we see the benefits tremendously in our patients because for second line before we used to use chemo with a very short PFS and short survival. Sotorasib is well tolerated, we have a good PFS compared with chemo. The only thing also is that there was a discussion about the toxicities. We have to be aware that maybe up to, if I remember, 10% of the patients may have grade 3 toxicities, that’s an important liver toxicity, LFT elevation, that we need to monitor. That’s why most of us use sotorasib, we don’t have a problem, the patient gives consent, but we need to monitor the liver function tests because this is still our intervention. It’s still second line because 40% response, more or less, with sotorasib is not enough to be first line. So the patients with KRASG12C will get first chemo-immuno and in second line we will give the sotorasib. The next drug that everybody always talks about, adagrasib, is waiting for FDA approval so it will not be a surprise that maybe by the time you are seeing this video it’s already approved.

Anyway, these were the most interesting presentations that I can mention in a short time. It was a pleasure to be with you. Until next time.