Hi, my name is Luis Raez, I am the Medical Director of Memorial Cancer Institute that is part of the Memorial Healthcare System, it’s part of the public healthcare system in Miami, Florida. I want to talk today about ASCO updates 2020.
I think it’s very relevant that we talk a little bit about small cell lung cancer. Small cell lung cancer is a very important topic because, as you know, for years it has been a disease that has been left behind with very few progress. We still have around 13% of patients with small cell lung cancer, around 30,000 people probably in America a year, that is why it’s very important. As you know, the standard of care for many years has been the use of platinum-etoposide for more than thirty years for this disease. Finally, last year we were able to add, as part of this standard of care for extensive disease, atezolizumab, thanks to the study called IMpower-133 that shows that when we add atezolizumab to the platform of combination of platinum-etoposide patients have an improvement of overall survival of two months. The hazard ratio is around 0.7, meaning that there is a 30% benefit in the survival adding atezolizumab for patients with extensive disease small cell lung cancer. Also atezolizumab is well tolerated so that allows us to use it as a maintenance therapy for small cell lung cancer, something that we never had before.
Last year also, if you remember ESMO, we had the presentation of a study called CASPIAN. In the study called CASPIAN, that has several cohorts or arms, basically we explored the use of durvalumab, another checkpoint inhibitor that is well-known because it is standard of care for stage 3 non-small cell lung cancer as consolidation. We explored adding durvalumab to the platinum-etoposide platform for extensive disease in small cell lung cancer. As you know, the results were positive. That’s why this word, CASPIAN, is very popular because that’s the way they remember the study. We know that adding durvalumab to extensive disease in small cell lung cancer, patients can live as overall survival two more months with a strong hazard ratio.
This year in ASCO there was a very important update of CASPIAN because, as I said, CASPIAN has several cohorts or arms. There was another arm that we tried to enhance the response with these immunotherapy agents and in that arm we not only used durvalumab but also we used tremelimumab, that anti-CTLA-4 antibody. Our hope was that adding tremelimumab will increase either the response, the duration free survival or the overall survival in these patients. As you know, the results are negative, as was presented in ASCO 2020. Adding tremelimumab, anti-CTLA-4, did not add more benefit to durvalumab for extensive disease in small cell lung cancer, so that’s why we are going to keep durvalumab for now as part of the standard of care.
However, there was some more good news for small cell lung cancer. As you know, for example, we have ECOG – ECOG is our co-operative group in the United States. ECOG presented a randomised phase II study. In this study they add nivolumab to the platinum-etoposide platform and adding nivolumab increased the disease free survival and increased the overall survival of these patients. So that is why it’s very encouraging data with a strong hazard ratio, showing the benefit of adding nivolumab to platinum-etoposide as part of the standard of care for this disease. You can criticise the study saying, well, this is a phase II study, it’s not a phase III study, but it’s a randomised phase II study with statistical significance. Nowadays, the FDA sometimes is making exceptions approving agents without need to do the phase III with a commitment that later the phase III will be done. So I don’t know what’s going to happen with this agent, nivolumab, but it’s up to the FDA and the European Medical Agency to see if it’s going to be approved or not or they want to wait for the phase III randomised data.
Finally, also we have a study called KEYNOTE-602 with pembrolizumab because everybody was wondering what happened with pembrolizumab. Pembrolizumab, when it’s added to platinum-etoposide, improves the progression free survival for these patients with small cell lung cancer. The overall survival is officially negative, despite the fact that it looks like the hazard ratio is positive. Apparently the statistical significance is not enough, as per the statisticians, so officially the overall survival is negative.
But anyway we are now very happy that small cell lung cancer patients in the frontline can use atezolizumab based on IMpower-133, durvalumab based on CASPIAN, on top of chemo and who knows if they will be able to add nivolumab and pembrolizumab with the data that was presented in ASCO.
For second line, third line, we already have nivolumab and pembrolizumab approved before. So hopefully with all of these approvals and information, the outcome of small cell lung cancer patients will improve. We are very familiar with checkpoint inhibition, toxicities and management of toxicities. So adding one of these checkpoint inhibitors is not detrimental for the quality of life of the patients. On the contrary, it helps for the maintenance part to prolong their survival. Thank you.