WCCS 2016

The role of chemotherapy for metastatic melanoma

Prof Paul Lorigan – University of Manchester, Manchester, UK

I gave a talk on the role of chemotherapy in metastatic malignant melanoma. I think the fact that it was the only talk on that subject at the conference shows that it’s not as popular a topic as it was before. The question was with all the advances in the treatment of melanoma whether there is still a role for chemotherapy in some patients.

What do you see as a logical next step?

The major point is that there have been huge advances in the treatment of melanoma over the last six years and these have come from advances in immunotherapy and in targeted therapy.  Prior to that we had spent twenty years trying to advance chemotherapy with little or no benefit really and the question is with the great progress we’ve made within modern therapies is there still a role for chemotherapy? There are certain sub-groups of patients who do less well with immunotherapy and targeted therapies, specifically the UVL melanomas, the eye melanomas. They don’t respond to immunotherapy; they don’t respond to targeted therapy; but unfortunately they don’t respond to chemotherapy either so it doesn’t really have a role there. Another sub group are patients with mucosal melanoma who do respond to immunotherapy but only about 50% as well as if you had a skin melanoma and there are a small group of those who respond to targeted therapy.  Some of those might get a benefit from chemotherapy. It was trying to identify is there a sub-group. I think there are some patients for whom it would still be relevant and I’ve tried to show who those would be. 

Then I talked a little bit about where do we go from here with chemotherapy. We can apply the same discovery techniques that we have for the modern treatments, so molecular profiling etc, but really we don’t have effective drugs. Unless we make a big step forward in chemotherapy drugs or unless we identify some specific targets that respond then I think we’re very unlikely to make the same sort of progress with chemotherapy that we have with the other treatments. So it wasn’t a very positive outcome really.

What are your thoughts on combination therapies?

Specifically with chemotherapy I think that that has little role to play. If you’re looking at the competition on the field it really is still on the substitute’s bench really. If you are looking at the good treatments that we have in melanoma -  targeted therapy or immunotherapy - we’ve had a lot of debate about that - how to use those, how best to use them either in combination or in sequence. I think that’s unresolved at present, still the subject of trials.  But actually that’s a difficult issue because it’s a live question and we have to address this to patients every day but we don’t have the data to advise them by.

Any thoughts about the conference?

There’s been a lot at this particular conference, as there is at all melanoma conferences, about side effects with immunotherapy versus benefit. I think an interesting picture that’s coming out is that the patients who get more toxicity seem to do better. Now that might be intuitive because the side effects are due to the immune system being activated and it might be that that’s a surrogate for more activity but that seems to be coming out in an interesting sort of way, interesting as a clinician and also to be able to reassure patients that if you have to stop treatment early because of side effects you’re not necessarily compromising their outcome. Many of the treatments we are giving now are becoming chronic treatments and so treating patients for one or two years, it’s a major undertaking both for hospitals, in terms of resource, but also for patients, the commitment to coming. Whereas that short, sharp shock, patients will often say ‘I am happy to commit to three months of intensive treatment’ and deal with all the problems upfront.  In terms of cost effectiveness as well, in fact it might be a cost effective way to treat people that they have more side effects upfront but you are giving less treatment in total.

What are your thoughts on hyperfractionation?

Yes hyperfractionation, I am not a radiotherapist but it’s proven in some tumour areas and we had a big study recently in small cell lung cancer looking a hyperfractionation which didn’t show an improved outcome actually.