ASCO 2021: Lung roundup

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Published: 5 Jul 2021
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Dr Luis Raez - Memorial Healthcare System, FL, USA

Dr Luis Raez speaks to ecancer about some prominent presentations from ASCO 2021 regarding lung cancer. He says that the theme for lung cancer this year was immunotherapy. Initially, Dr Raez talks about studies regarding neo-adjuvant immunotherapies.

He discusses CheckMate 816, IMPower010, the 5-year update from PACIFIC Trial and CheckMate 9LA.

In the end, he mentions that after seeing the results from these trials, there is a lot to think about the future of adjuvant and neo-adjuvant immunotherapies in lung cancer.
 

CheckMate 816
IMpower010
PACIFIC Trial
Checkmate 9LA

 

Hi everybody, my name is Dr Luis Raez, I am the Medical Director of Memorial Cancer Institute at the Memorial Healthcare System here in Miami, Florida. I am very happy to share what have been the best ASCO presentations in the field of lung cancer, mainly all of them are about immunotherapy this year, 2021. I’m very excited for this invitation from ecancer and I’m very grateful for the educational effort that ecancer puts into doing these videos for the benefit of all of you and our patients.

Mainly this year in ASCO 2021, as I said, lung cancer the main field was really immunotherapy. First of all we are going to talk about neoadjuvant immunotherapy. As you know, we don’t do neoadjuvant immunotherapy as a standard of care yet. However, in the last two or three years we have had several presentations in the area of neoadjuvant immunotherapy, meaning we give immunotherapy before surgery. Why are we doing that? We are doing that because we are trying to find if we can shrink the tumour and we can get a good complete pathological response before surgery. We can assess easily during the surgery when we evaluate the specimen.

In this ASCO there was a very important presentation, if you remember, it’s the one that we call CheckMate 816. Why is this so important? Because CheckMate 816 was presented actually even in AACR, two months before ASCO. CheckMate 816 is important because despite the fact that, as I said, there were five or six phase II studies about neoadjuvant immunotherapy in the last two or three years, they were only phase II so nothing changed in standard of care. But CheckMate 816 is very important because they are comparing three cycles of chemo and immunotherapy versus chemo before surgery. If you remember the presentation from ASCO there was a 54% response rate when we add immunotherapy compared with 37% if we only do chemo alone. But the most important thing was not that. The most important thing is that the complete pathological response that we see at the time of surgery, when we give only chemo the complete pathological response is around 2%, when we give chemo-immuno the complete pathological response is 24%. So it’s amazing, it’s twelve times more only because we added three cycles of nivolumab. The same with the major pathological response. If you remember, major pathological response is if there is less than 10% of viable tumour. It went up from 9% to 37% if we add to the chemo the immunotherapy. So that’s why it’s very exciting for us. This is the first, as I said, randomised study showing that there is a benefit in neoadjuvant immunotherapy with chemo for lung cancer. We are waiting for the FDA to see if this is enough to grant them approval because we don’t have overall survival data yet because it’s early.

The other exciting presentation that was in the plenary session was IMpower010. IMpower010 is immunotherapy with atezolizumab after surgery. As you know, immunotherapy is not standard of care also for adjuvant therapy, the only standard of care is chemo and if you are EGFR positive we give you osimertinib. But in this study they randomised patients, the stage 1b, 2 and 3, and after they have the proper surgery and they have chemotherapy they randomise them to give the atezolizumab versus observation that is the current standard of care. If you remember the presentation from ASCO, if the patients have a PD-L1 of more than 1% there was a 34% benefit in the disease free survival hazard ratio, 0.66, if we add atezolizumab for one year after surgery. So that’s a very impressive result. The endpoint of this study that we got in ASCO was the disease free survival and we got the disease free survival for the 1% patients and we also got the disease free survival presentation for all the patients that are stage 2 and stage 3, they are the ones at higher risk of recurrence, and the hazard ratio was 0.79, meaning that there is a 21% benefit if we add atezolizumab after surgery. The same thing as the other study – what is the FDA going to do with this? This is not overall survival, the overall survival data is not ready yet. Maybe the FDA can give a conditional approval to this agent for neoadjuvant or adjuvant to have finally the overall survival data. But these studies are in early stage lung cancer, the overall survival data may take a lot of years. That’s why it’s better to assess the outcome of these studies with disease free survival or major pathological response, as we did in the previous study.

The third study that was very interesting is the PACIFIC trial five year update. If you remember, standard of care for stage 3b patients is to have chemoradiation followed by one year of durvalumab. That was established by a trial called PACIFIC that is very popular, everybody knows. But the exciting thing in this ASCO is they presented a five year update. After five years that we are doing this study with one extra year of durvalumab there are 43% of patients alive if you get immunotherapy with durvalumab versus 33% if you get only chemoradiation, our old standard of care. So there is a 10% benefit even after five years if we add immunotherapy, that’s why immunotherapy is our standard of care and we are very glad that that has been seen again.

Finally the other exciting or interesting presentation in immunotherapy for lung cancer is for stage 4. For stage 4, as you know, we have carboplatin/pemetrexed/pembrolizumab, we have single agent pembrolizumab, single agent atezolizumab. We have a new single agent called cemiplimab. All of these immunotherapies that we use for stage 4 is when the patients don’t have actionable genes - first of all we’ve had to test for actionable genes. However, in the last two years we are using ipilimumab and nivolumab as an option for patients that have PD-L1 more than 1%. So, as we know, we are doing this for PD-1 more than 1%, ipilimumab/nivolumab if you don’t want to use any chemotherapy, it’s already approved by the FDA and other regulatory agents.

What is only new from this ASCO is that they presented a two-year survival update of a study called CheckMate 9LA. 9LA is the ipilimumab/nivolumab but instead of giving the ipilimumab/nivolumab alone we use two cycles of chemotherapy. So instead of giving ipilimumab/nivolumab alone we combine ipilimumab/nivolumab and for the first two cycles we give chemotherapy because there may be patients that need the chemo to have a faster response, maybe, than immunotherapy. The two-year update presented at ASCO shows that the survival of these patients is 15.8 months compared with 11 months if we do conventional chemo. So that’s why there is a benefit in survival, the hazard ratio is 0.72, meaning that there is a 28% benefit combining ipilimumab/nivolumab with chemo for at least two cycles. So that’s why that was a benefit from immunotherapy.

With these presentations we have a lot to think about for this year because the first two are the most important ones, the CheckMate 816 and the IMpower010. The FDA has to decide if we are going to make them part of our standard of care, neoadjuvant immunotherapy or adjuvant immunotherapy. This has been a very exciting year for our patients. Thanks for your attention.