Immunotherapy developments and new agents for locally advanced NSCLC and SCLC

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Published: 8 Jul 2023
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Dr Edgardo Santos - Florida Precision Oncology, Florida, USA

Dr Edgardo Santos speaks to ecancer about immunotherapy developments and new agents for locally advanced NSCLC and SCLC. 

Dr Santos discusses what is the current standard of care and what is in development for the treatment of lung cancer.

He discusses in detail the data from the PACIFIC, PACIFIC2, PACIFIC6, PACIFIC8, NICOLAS, KEYNOTE-799, SKYSCRAPER-003 and LAURA trials.

Dr Santos concludes by discussing the importance of holding events such as the Best of ASCO. He also explains the aims and objectives of FLASCO, which is the Florida Society of Clinical Oncology.

Can you tell us about your presentation tomorrow?

So, in locally advanced non-small cell lung cancer there was a presentation which was a poster discussion on Pancoast tumours. Basically, the area here was to use a high dose radiation therapy and the outcomes looked very promising. Not too much in this particular area in which the patients are unresectable. So tomorrow I am going to speak on what is the standard of care today and what is in development. So in future congresses, either ASCO next year or ESMO this year, we will listen to those things that I will present tomorrow. 

For those patients that are borderline there was a lot of data which I will not discuss tomorrow which is on the issue of neoadjuvant chemoimmunotherapy followed by surgery or sometimes a different approach in that regard or what we call now perioperative immunotherapy which includes neoadjuvant chemoimmunotherapy followed by surgery followed by immunotherapy. So there was a lot of data presented at ASCO this year.

But my topic tomorrow, again, is those patients that are already unresectable, so stage 3a unresectable, stage 3b and stage 3c. At this moment the standard of care is the PACIFIC trial and very well established, improved overall survival as well as the progression free survival as we have seen in the last five years. So there are a lot of gaps that came after PACIFIC such as, for example, what to do with patients that have poor performance status. That is an ongoing study called PACIFIC2 which is done outside of the USA. Basically, patients receive similar to what they received in PACIFIC except that it’s a sequential approach. Once the patient is randomised one group goes to receive placebo, the other group will receive durvalumab in maintenance. So that is PACIFIC2, already finished, we are waiting for the results.

Another thing is what to do with immunotherapy like, for example, put immunotherapy on board with concurrent chemoradiation then followed by maintenance therapy. There are also studies ongoing such as the PACIFIC6 is one of them. There is another large trial with more patients, those are in development and they are ongoing. There is another study called the NICOLAS study, which is nivolumab plus concurrent chemoradiation followed by nivolumab, that has also been published recently with very good results. 

The other issue here is how to apply chemoimmunotherapy before concurrent chemoradiation. There are also trials such as KEYNOTE-799 which already met its primary endpoint which was overall response rate and grade 3-5 pneumonitis. That is also moving forward in another big clinical trial. So, as you can see, we are trying to move all these issues of chemoimmunotherapy or immunotherapy and then adding before concurrent chemoradiation. That’s the idea. 

But the most striking thing is how to improve, again, on what we have got from PACIFIC. There are two new medications, one is oleclumab which is an anti-CD73, there is another one called monalizumab which is an NKG2A. What do they do? So when we give radiation therapy to the tumour there is an overexpression of PD-L1 but, besides that, there is also upregulation of CD73 which is going to cause adenosine in the extracellular domain. That adenosine causes a decrease in the immunity. So this oleclumab is an anti-CD73, the idea here is to boost the immune system. 

On the other side, the monalizumab, which is an anti-NKG2A, what it does is avoid this particular ligand that is in the active T-cell and in the natural killer cells to get to the receptor which is going to shut down the NK cell. So by blocking that interaction we are again boosting the immune system that gives us tremendous overall response rate, tremendous PFS and also a better disease control rate over durvalumab alone in the maintenance. So, again, it’s the backbone from PACIFIC but when you move to maintenance, durvalumab alone, you add either oleclumab or monalizumab; that’s the COAST trial. Based on that phase II randomised trial there is the PACIFIC9 ongoing now with almost 900 patients, if I’m not mistaken. The same study as the phase II now in the phase III and proves that concept. 

Besides that, we are going to also discuss about TIGIT, which is another checkpoint inhibitor on the T-cell, how to block the interaction between the ligand, the TIGIT, and the receptor PVR. So there are monoclonal antibodies also in development, a clinical trial called SKYSCRAPER-003. Basically concurrent chemoradiation, randomisation between tiragolumab plus atezolizumab versus durvalumab. So this arm is like the PACIFIC, trying to compare with atezolizumab plus tiragolumab. 

There is the PACIFIC8 trial, you see everything is like PACIFIC. The PACIFIC8 trial we basically will add a similar thing that we saw in PACIFIC but we will add to durvalumab an anti-TIGIT medication called, if I’m not mistaken, domvanalimab – it’s a long name. So this is what’s going on now in concurrent chemoradiation.

Finally, it’s a long topic, what to do for those patients who have EGFR mutation and ALK mutation when we know that those patients will not do well on durvalumab maintenance? So for that there is a study called LAURA that already finished accrual. We are waiting for those results. In the LAURA only EGFR mutant patients participated so basically those patients that receive concurrent chemoradiation, they were randomised to receive osimertinib versus placebo. We are waiting for the readout of that study. So that is the topic of locally advanced non-small cell lung cancer.

What is the importance of holding events such as Best of ASCO, or FLASCO events?

The Best of ASCO is sponsored, as I mentioned before, by Memorial Cancer Institute and then ASCO, which is the American Society of Clinical Oncology. We are going to present data presented in ASCO and we have a chance to talk about the small cell lung cancer, which is the other topic that we have a lot of data in small cell lung cancer presented at ASCO this year. But it’s important because we give the opportunity, number one, to deliver the more important aspects from the congress. Not all our colleagues are able to go to ASCO because of conflicts of scheduling or you also need to go to another city and travel and those kinds of issues. So it’s important that we come here to Miami. There are two bits of ASCO, one here in the south, one in the north. So Florida has the chance to get the latest news from ASCO.

Now, in terms of FLASCO, which is Florida Society of Clinical Oncology, it’s an organisation in which I am the Treasurer, very humbled and honoured to be the Treasurer of this FLASCO and also the President of the FLASCO Foundation. So what we do in FLASCO is help patients with cancer and help also our colleagues in different ways. At least from the FLASCO Foundation, which I’m going to speak for, we do activities, we try to collect funds and try to help patients affected by cancer. Because when a human being is affected by cancer it’s not only the patient, it's also all the family. So we try to help them. We also give grants to different non-profit organisations that also help people suffering from cancer. So that is what the FLASCO Foundation does. 

Then FLASCO as a global, what we do is be on top of healthcare policies, trying to be on top of those issues that may affect the delivery of the most appropriate care for the patient. That is basically what FLASCO does – trying to deliver the best care to the patient in different ways and also to keep our colleagues on top of all the news in science. 

We have two big meetings, one in the fall, one in the spring, in which we collect all our associates, which, by the way, we are more than 4,000 associates at FLASCO which includes not only medical oncologists and haematologists but also APP, advanced practitioners, pharmacies in all the areas, oncology – that could be an oncology nurse, a nurse practitioner in oncology – and also administrators. So we put all families from healthcare that we deal with cancer in one session twice a year and we discuss several topics. 

Then for the patients we also have seminars, sometimes up to ten seminars per year, in different cities around the state of Florida. So that’s what we do in FLASCO.