Moving precision medicine for lung cancer into the adjuvant setting

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Published: 6 Jul 2015
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Dr Don Gibbons - The University of Texas MD Anderson Cancer Center, Houston, USA

Dr Gibbons talks to ecancertv at WIN 2015 about the SUMMER trial [(Elimination of relapse through innovative adjuvant targeted therapies in Stage II and III NSCLC) 

The trial’s design, which is currently being finalised by the WIN Consortium, is novel in that it will look at precision medicine and targeted therapies in the adjuvant rather than metastatic setting and it has one study arm that will specifically look at the benefit of using combinations of immunotherapy targeted agents in patients with non-small cell lung cancer (NSCLC).

Moving precision medicine for lung cancer into the adjuvant setting

Dr Don Gibbons - The University of Texas MD Anderson Cancer Center, Houston, USA

What is the background for the SUMMER trial in Stage II and III NSCLC?

The SUMMER trial is part of series of trials that WIN is planning in extension of its current experience with WITHER. These are all focused around lung cancer and they are broken up based upon the different stages of the patients that come in. So the SUMMER trial is specifically meant for the adjuvant setting in which patients have had potentially curative resections and then postoperatively standardly they would get chemotherapy alone. In our case we’re planning that in the SUMMER trial they would get additional therapy to that. So the background that goes into that is that even though these patients are considered early to intermediate stage, roughly 40-50% of the patients, depending upon their actual stage, will still recur with either local regional disease or metastatic disease that will eventually claim their lives. So we are hoping to bend the survival curve in that particular group of patients by changing the therapy that they’re receiving in the adjuvant setting.

How is the SUMMER trial similar to or different from other trials such as WINTHER and the BATTLE trials?

It’s different than many of these because many of these are in metastatic patients. So, for instance, the WINTHER trial that is currently being conducted by WIN as well as the BATTLE trial that was conducted, the first BATTLE trial, that was conducted at MD Anderson and the current iterations of that that we have in MD Anderson. Those were all in metastatic patients, this is hoping to move forward those particular concepts into the adjuvant setting for patients who have earlier stage disease and have received potentially curative operations.

Can you outline the design and methods being used in the SUMMER trial?

In this case the design is not completely finalised, in fact in our planning meetings yesterday this was a big topic of discussion. But the overall idea here is that we are trying to position this versus some of the other trials that are ongoing such as ALCHEMIST in the United States. Currently the design has three arms: one is an observation arm so it would be our current standard of care so that we have a good arm for comparison. One of the arms is with immunotherapy only after patients receive standard adjuvant chemotherapy, that will be similar to the NCIC BR31 trial that is currently ongoing in Canada and other countries and will also be similar to the NCI ALCHEMIST with the nivolumab treatment that is planned but not yet approved. However, the real distinction here is in our third arm: the third arm patients will be receiving immunotherapy targeted agent combinations and that’s really a unique setting in which there are no other groups that we’re currently aware of that are applying that in the adjuvant context.

You mentioned the ALCHEMIST trial, can you briefly give an overview of what that trial is set up to look at?

ALCHEMIST is a big National Cancer Institute supported effort in the United States that is screening between 6-8,000 lung cancer patients; this is specifically for the adenocarcinoma histology. That large number of patients is being screened with deep molecular profiling so that we have significant amounts of science but in addition to that the current targeted therapies that are being applied such as anti-EGFR therapy for patients that have an EGFR mutation or ALK translocations, those are relatively small percentages of the overall screening population.

There is a proposal and the trial is currently being written for an immunotherapy arm with the approved drug nivolumab for patients who do not have a molecular match either with an EGFR mutation or an ALK translocation.

What is the SIMS (Simplified Interventional Mapping System) algorithm being used in the SUMMER trial and what are its advantages and disadvantages?

The SIMS algorithm was developed by the WIN Consortium and this is an algorithm that tries to take into account additional information beyond the DNA mutations. So standardly, in today’s world and from a clinical standpoint, when we see lung cancer patients or patients with other diseases as well we are specifically looking for particular DNA mutations that we believe to be driver mutations. The SIMS algorithm tries to build upon that by not only taking into account the DNA mutations but also transcriptomic profiling in terms of the mRNA levels, copy number variation changes and we’re planning additional layers to be added on to that such as proteomic based analyses with the idea that this gives us overall a much better readout of what sort of dependencies particular tumours have beyond just the DNA mutations.

So what progress has been made with the SUMMER trial so far?

It’s not up and running yet, we’re still in the planning stages of this. As part of the WIN Consortium the WINTHER trial is up and running and accruing quite well and has allowed us to develop the framework that we need for analysing the tumours and running these sorts of innovative trials across continents and across 17 different countries to date. So for the next iterations of the trials, the BOOST trial, the SUMMER trial and the SPRING trial, those are all in the planning stages so all of them are in the later stages of planning with the hopes that in the next 6-12 months we will have those up and starting to accrue patients.

What results do you expect, or hope, to see?

Overall our big goals are that we really want to change our ability to provide good, targeted agents in terms of a precision medicine based model for many more patients. We hope that in terms of outcome what that provides, specifically in the context of SUMMER, is that we are increasing the cure rates and therefore overall survival. In terms of the more short-term endpoints we are specifically targeting the twelve month or one year disease free recurrence rate with the idea that this will impact longer term survival in this particular group of patients.

What is your final take home message?

When good, large, international groups like WIN get together that that will allow us to put together innovative strategies such as this so that we can reach out to more patients. Part of the reason that WIN has been successful to date and I think eventually will be even more successful and impactful is that it’s not just the academic community, it’s the combination of academics working with governmental agencies and regulatory agencies and with a strong collaborative component from industry so that we’re really designing the very best patients across many continents to reach out and change how we treat cancer.