ESMO 2014 Editor's roundup

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Just back from Madrid, wonderful ESMO meeting – a bit of sunshine, a bit of rain. Lots and lots of people and inside a really fabulous conference centre - marvellous, marvellous illustrations, colour photographs of current and previous ESMO personalities; beautifully staged and a nice warm feeling to it. A lot of overseas visitors, which was very welcome indeed, from Asia, from Africa, from Arabia, from North America, and also one or two important studies being reported, particularly from North America.

On the top of my list, it’s short because Giuseppe Curigliano has written his usual extensive and first class conference report which you can read in ecancer, a couple of interesting supportive care presentations. Supportive care is usually at the bottom of every agenda, along with quality of life and psychological support, and there are two new drugs. One of them is anamorelin and this has been shown in a nice large randomised trial to improve appetite in patients with cancer cachexia associated with non-small cell lung cancer, improvement of weight and in some patients also muscle mass, so very important supportive care because of this distressing problem of cachexia. And a second patient-focussed, good news for patients who are getting cisplatin is that another drug called rolapitant is shown, again a nice big study, randomised, to cut down nausea and vomiting in patients getting cisplatin. The important thing about this presentation was that it’s not just the acute effects of cisplatin that this drug seems to appease but also the late effects. Any patient with cisplatin will tell you that even two, three, four, five, six weeks after cisplatin they still feel very nauseous. So that’s the two supportive care abstracts which I’ve picked up.

Then three Cinderella charities, just an inkling of some movement in the right direction – cervix cancer, mesothelioma, head and neck cancer. In mesothelioma, a not very much studied cancer of the pleura, there has now been evidence that in a number of these tumour samples there’s evidence of PDL1 which could be a target for all the five new anti-PD1, anti-PDL1 and anti-PDL2 drugs which are showing so much success in melanoma. In cervix cancer there has been good data, encouraging responses, from angiogenesis inhibitors and a new one was mentioned at ESMO. We’ve evidence of efficacy of bevacizumab as an anti-angiogenesis drug in advanced cervix cancer in combination with chemotherapy and here’s a second one called cediranib and in a randomised trial it improved progression free survival in metastatic patients. Then in head and neck cancer, again a small molecule, second line, afatinib, improving performance in progression free survival in metastatic head and neck cancer. So those were the three Cinderella drugs.

Then the two big hormone dependent drugs for prostate cancer and breast cancer, the final results of a randomised trial in men who have castration resistant prostate cancer metastases and this was a trial of abiraterone and prednisone up front before chemotherapy, so chemotherapy-naïve patients. The bottom line is that there’s a maintained survival benefit, a big survival benefit, for this combination. The trial was ‘stopped’ early because of a widening gap in favour of abiraterone prednisone, but the investigators carried on to the end, followed every single patient, noted that a lot of patients crossed over to abiraterone and prednisone and despite that crossover there still was, at the end of the day, after 96% of the deaths in the trial, a clear-cut advantage for abiraterone and prednisone. So this is very important in castration resistant prostate cancer.

Then in breast cancer an important study too because it’s beginning to attack this issue of HER2 new resistance, so patients who get trastuzumab or other HER2 active drugs and then get resistant, and not all of those patients surviving in the first place. So there must be more to HER2 new than meets the eye and there are a nice couple of studies, one of which may explain part of this resistance and the finding of PIK3CA mutations in these HER2 positive breast cancer patients’ tumours. There’s evidence, all retrospective, none in randomised trials, that this mutation might blunt the effect of anti-HER2 therapy. But for the patient right now it’s more important to report the results of pertuzumab added to trastuzumab, a dual anti-HER2 therapy. This is a study called CLEOPATRA and it randomised HER2 breast cancer patients to get trastuzumab and chemotherapy or the same plus pertuzumab, so another anti-HER2 drug probably working with a different mechanism. The answer is quite spectacular – a sixteen month survival benefit to the triple therapy approach compared to standard. So this is practice changing.

A couple of really interesting reports on mutations in HER2 new in 2-3% of non-small cell lung cancer patients. Now that is, of course, very small but there are an awful lot of patients with non-small cell lung cancer so that converts into a fair size population and this obviously opens up the door to picking these patients out with molecular diagnostics and then giving or offering the appropriate anti-HER2 medicine. The same approach, another very small percentage of the non-small cell lung cancers, that’s 2% maybe, maybe 3%, have got a BRAF V600 mutation. This, of course, has been the massive finding of the last three or four years in melanoma and now it seems that we’ve got an inkling that the same mutations might occur in a small number of non-small cell lung cancer patients. This also gives an opening for specific targeted chemotherapy.

The most innovative approach to selecting patients for targeted therapy was reported from Kings College, London. I’m a visiting professor there so I admit a bias straight away. This was the use of a folate scan in order to select patients for an anti-folate, vintafolide. This was done in a nicely controlled way with patients being randomised to the new drug, the vintafolide, which by its name is clearly a folate targeted drug, versus docetaxel and they used the imaging technique which picks up folate receptors in tumours and they found a correlation. It’s a small study but what’s interesting is that it shows, in fact, another approach to selecting patients for targeted therapies, other than digging into the tissue and the omics, the genomics or the proteomics. Scanning is non-toxic, it’s non-invasive, is much appreciated by patients and I hope this will be the beginning of a whole range of targeted imaging studies which will help select out patients for specific drug treatments.

Last but not least, melanoma. Melanoma continues to get the headlines because of the remarkable outbreak of new drugs targeted against BRAF mostly but also another number of interesting targets which are coming up. We know now that one can get responses with anti-BRAF drugs and we know we can get responses for anti-cytotoxic T-cell responses. Now we’ve got data on combinations of drugs, for instance the BRAF inhibitor vemurafenib together with cobimetinib in aggressive metastatic melanoma showing significant progression free survival over the single agent vemurafenib. Another combination study showing trametinib and dabrafenib versus vemurafenib alone, so two versus one seems to be holding up two or three months increased response rate and, inevitably, survival too in these advanced melanoma patients. But showing that drugs which are targeting different pathways, BRAF and MEK, one or two others, are actually producing clinical data. Small steps but will take us further down the line.

That’s it for Madrid; I recommend you to read Curigliano’s conference report. Thanks very much.