European Multidisciplinary Conference in Thoracic Oncology (EMCTO 2011) 24—26th February 2011, Lugano
Maintenance treatment for advanced non-small cell lung cancer
Professor Filippo de Marinis (Azienda Ospedaliera San Camillo Forlanini, Rome Italy)
I’m joined now by Professor Filippo de Marinis here at the Multidisciplinary Thoracic Oncology conference in Lugano. Filippo, you’re talking about a concept, not just one treatment but the concept of maintenance treatment. There’s a big debate whether or not you should use maintenance treatment on patients but, first of all, in the context of non-small cell lung cancer what constitutes maintenance, what is maintenance?
Many thanks for this question because it is very interesting and is useful for clinical practice. So, up to now the standard treatment of first line for advanced non-small cell lung cancers were represented by an induction chemo realised with four cycles for patients with stable disease or six cycles at maximum for a patient responder. And then some wait and wait time for the toxicity of the chemo and for the negative results obtained to prolong the time of first line realised with chemo and especially with the doublet platinum based with third generation drugs. So this is the historical approach and the standard approach: 4-6 cycles at the beginning and then stop for patient responders, for patients stable.
And then, of course, the question is what do you then do?
Yes. So maintenance is a new paradigm where it’s possible to prolong the treatment all with chemo, all with new biological molecules, targeted therapies; to prolong treatment in absence of toxicity for a fixed number of cycles or until disease progression.
So could you take me through the scheme of things? You begin with the patient, you have a diagnosis, you then prescribe primary therapy, first line therapy. You then get to the end of that therapy, now how do you take the patient through that? Begin with a typical patient.
OK. We have different options considering the first line treatment. If I realise induction chemo with doublet platinum based for four or six cycles and I want to apply the maintenance strategy, I have two possibilities: I continue one of the drugs used in the induction therapy or I use another drug. And this other drug can be chemo or molecular or biological molecular.
And at that point, what…?
But we have also another option because if, as induction, I used a chemo plus bevacizumab, very useful in the US, or cetuximab, not yet approved in Europe, the maintenance treatment is representing a continuation of the bevacizumab or the cetuximab. So this is a maintenance continuation of one of the drugs biologically used in the first approach because the first approach can be represented by chemo alone, the most part of the regimen used in Europe, or chemo plus bevacizumab, very, very useful in the US.
So initially, then, you can go with the biologic, you can continue that, and there are data to show that that has some benefits in consolidation or in maintenance. How does the status of the patient with respect to response affect your decision making and which choice of agent at that point when you finish the initial therapy?
We have some difference among the large population of patients because we have, in clinical practice, some patients that want to have other possibilities, especially after an initial response because in the mind of the patients I am fighting with the cancer and at the end of the induction therapy if I obtained a response, it’s very crazy to stop all therapy because the response was good. The mind of patients is, ‘OK, after this initial advantage, continue.’
And the mind of the doctor?
Yes, and they ask the doctor to have other possibilities, to continue immediately the therapy, not waiting for the second line opportunity for the metastases. So maintenance is a concept that is good for clinicians but it’s good maximum for patients.
And the patient who has stable disease is in a similar category?
Yes, because the stable disease is a historical problem. Stable disease is not an advantage, it is not a progression. What is stable disease? The prognostic role of stable disease, what is it? We don’t know because stable disease can represent, in the same time, no response and no response is a negative result. So stable disease is positive or negative result, this is the question at the debate. But for this particular group of patients I think give you an opportunity to prolong a treatment without toxicity, if no toxicities present. Trying to obtain some response, an advantage, now is a great opportunity for these kinds of patients.
And the patients who do not achieve a response and are not maintained with stable disease but their disease continues to progress, how do they view further therapy?
Second line, because this is a negative group of patients that can receive immediately another treatment, namely the second line treatment. The problem is not for these 25% that the end of induction therapy is evaluated as progressed but the problem concerns the other 75%, all the responder patients, this big number of patients evaluated as stable disease.
So the question, maintenance treatment – yes or no? What is the answer emerging here from Lugano?
From Lugano is emerging new opportunities and new data. Up to now we have two trials, very important, one realised with pemetrexed in a switch maintenance study where pemetrexed was given immediately after an induction of different chemo, it realised a very impressive PFS advantage. Another opportunity is given by using erlotinib after chemo, it has emerged from the SATURN study and erlotinib offered, for stable disease patients, a new opportunity. But not from Lugano but from the next ASCO meeting in Chicago, will find the results coming from the PARAMOUNT study where pemetrexed is given immediately after the end of cisplatin and pemetrexed is given as a first line. So the real maintenance, I start with the cisplatinum pemetrexed and I continue with pemetrexed. I participated in this study, we sent the abstract to ASCO so I think that it could be a new, very important opportunity for patients.
And briefly the doctors should be learning from all of this what sort of practical message?
Practical message is consider the opportunity to continue treatment but avoiding toxicity. And for patients that want to have more results, but considering the patients, not considering the tumour.
And biologics float to the top of these therapy options?
Yes, biologic is an opportunity. I think that up to now we have not had very big results with the exception of erlotinib; we have only the bevacizumab results. But the future is represented by targeted therapies.
Filippo, thank you very much for joining us here on ecancer.tv.