In my session I was co-chairing my table with the main investigators in the field of small cell lung cancer. There was Charles Rudin talking about the basic result; there was also Silvia Novello talking about recent advances in immune therapy and Corinne Faivre-Finn talking about radiotherapy and myself talking about recent advances in targeted agents. So my talk was quite challenging because, compared to non-small cell lung cancer, small cell lung cancer has been lagging behind in terms of the development of targeted approaches.
What I tried to do in my session was to show the audience that there is a lot of things to do, there are new agents there, it seems, that can change the landscape of this disease. Some of them that I commented on that I thought are ones of the most important relevance is, for example, the antibody-drug DLL3 drug conjugate also called Rova-T. We have now results of the phase I trial that demonstrated significant and meaningful activity in those patients expressing DLL3 which is a protein that is over-expressed on the tumour cells, neuroendocrine tumour cells. We had last year in the ASCO meeting the results of the TRINITY study which is a study in patients treated with almost two lines of therapy. In this study the activity was not as high as they were expecting with an overall response rate of 18% in those patients expressing DLL3. Right now we have to change for the ongoing trials, there are two ongoing trials right now, phase III ongoing trials – the MERU which is maintenance treatment after cisplatin etoposide and then in the second line setting we have the TAHOE trial which is comparing the standard topotecan versus Rova-T. Both trials are ongoing and we are waiting for the results to see if Rova-T can be a new standard of care in small cell lung cancer.
I also talked about new agents such as chemotherapeutic agents such as lurbinectedin which is a marine related compound. In a phase I and phase II trial presented last year and this year in the ASCO meeting they have demonstrated that is has activity, around 30% response rate, 20-30% response rate, in combination and as monotherapy. There is right now a phase III trial that has very recently, one or two months ago, finished recruitment and is a phase III ATLANTIS trial in the second line setting compared to topotecan compared to lurbinectedin plus doxorubicin. We are now waiting for the results to see if this can be also a new standard in the second line setting.
Other things that were not strategically targeted therapies but they are very important is the use of immunotherapy. As Silvia Novello remarked in her session, the standard of care in the first line setting of this disease has changed. We have this year in the World Conference of Lung Cancer and recently published in the New England Journal of Medicine there is the results of the IMpower133 trial comparing standard treatment with platinum etoposide versus carboplatin etoposide plus atezolizumab in first line setting of the disease and the trial has been positive for its primary endpoint, demonstrating an improvement in overall survival from 10 to 12.3 months with a decrease of a risk of death of 30% in those patients treated with a combination of chemotherapy and atezolizumab. This is important because we have been in this meeting some new information about the use of immunotherapy as monotherapy in the second line setting and the results have not been as positive as they expected such as the recently reported press release reported results of nivolumab in the second line setting of small cell lung cancer. So it’s important maybe in small cell lung cancer the activity of immune monotherapy is completely different to non-small cell lung cancer but right now it seems that the best option for these patients is to combine both approaches in the first line setting.
By way of conclusion can you tell me your thoughts, your feelings, what is the atmosphere and the expectation for people working in small cell lung cancer at this year’s conference?
There’s a lot of enthusiasm. We know now or we have admitted that small cell lung cancer is a completely different disease to non-small cell lung cancer, that we have to explore all the different approaches in the disease. I would say that now we realise that we have to explore combining strategies. Probably in small cell lung cancer we do not have to go for one single approach but we have to take the best of different approaches. New molecules using T-cell engaged approaches might be very useful or also by the use of DNA repair inhibitors, for example, or checkpoint inhibitors combined with immune therapy. That could enhance the activity or the response of immune therapy. Of course we have now the evidence that joining immune therapy and chemotherapy works in small cell lung cancer so we have in front of us a sea of options but we have to, of course, prospectively explore them and wait for the results of the phase III trials that were going to be released soon next year in the forthcoming meetings.
