ASCO 2014 roundup

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Published: 2 Jun 2014
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Prof Gordon McVie - ecancer and European Institute of Oncology, Milan, Italy

ecancer's Prof McVie provides a roundup of the main points of discussion from ASCO 2014.  

I’m Gordon McVie from ecancer and I’m reporting from ASCO about the highlights. I was presented this year with a yellow ribbon which said ’35 year member’ which produced mixed feelings but it does give me the authority to say that this was a good ASCO; we’ve had some bad ones in the past but this was a really good ASCO.

Let’s start with the two hormone sensitive cancers, the big ones, and start with prostate cancer. I think we may have a change of practice here because of a big study which showed that in adjuvant treatment of prostate cancer docetaxel plus the usual treatment, which is ADT, androgen deprivation therapy, was better than ADT and it’s significantly better. So I think if this is going to be rolled out, and I hope it will be, we’re going to have to have some changes in the way that neurologists talk to medical oncologists and the way that multidisciplinary teams tackle this new challenge. Inevitably there was good follow-up data on the two new kids on the block in castration resistant prostate cancer. The first one was abiraterone and the data continues to be good with good response rates and long term response rates and that’s really good news. Then the enzalutamide which was the other drug which hit the headlines last year at ASCO and that also continues to be good. However, neither of them are curative and it’s not clear which one you should use first. What seemed to emerge was that neither of them is good in second line, that they’re each better in first line. So inevitably there was a combination study, abiraterone plus enzalutamide, and that really was exciting. It wasn’t a big study and it wasn’t a randomised study but it did show that this was an exciting way forward in the treatment of CRCP in prostate cancer.

Then breast cancer, a couple of really big studies from IBCSG, one of them pretty disappointing – lapatinib doesn’t add very much to trastuzumab. The other one, well, pretty predictive, aromatase inhibitors are a bit better than Tamoxifen. In this case it was exemestane in younger women with hormone sensitive breast cancer combined with ovarian suppression. Exemestane was superior to Tamoxifen. Now that’s important if you’re in Western countries where you can afford Exemestane but I have to say that for a lot of the world Tamoxifen is still the gold standard and it looks as if, from this year’s ASCO, that ten years of Tamoxifen is better than lesser duration.

On the topic of ovarian suppression, LHRH analogue suppression of the ovaries with goserelin showed really quite encouraging effect in protecting the ovaries in young women, premenopausal women who got chemotherapy. I think this is also on its way to becoming a standard of therapy.

So, after the hormone sensitive cancers let’s deal with the other big one, that’s lung cancer. There, to my astonishment, was small cell lung cancer. We’ve heard very little about small cell lung cancer in the last twenty years, frankly, but here we had a demonstration that even in extensive disease small cell lung cancer irradiating the primary tumour was a good idea. It goes in other cancers similarly, get the bulk disease down and you can have an effect even on distant metastases. Then an interesting paper saying that primary cranial irradiation, that’s PCI, was actually not necessary in small cell lung cancer who didn’t have visible metastases on an MRI scan. So I think this is good news; I think it’s saying that instead of giving everybody the toxicity of PCI, assuming they’ve achieved some sort of remission with small cell lung cancer, chemotherapy and radiation therapy, check the brain status with MRI and if it’s negative then you don’t need to go on with prophylactic cranial irradiation.

In non-small cell lung cancer a couple of important things. One was in stage 2B/3 cancers when you treat with chemoradiation there has been a trend to give adjuvant chemotherapy after that. This was a randomised trial which says that is not actually adding anything except toxicity. Then a number of drugs, obviously, being tested in advanced non-small cell lung cancer; most of them are not much better than what we’ve got and that’s not saying very much, sadly. But ramucirumab came up with docetaxel as being better than docetaxel in terms of survival and that’s an unusual finding, an extension of survival in advanced non-small cell lung cancer.

In ovarian cancer we’ve seen over the last couple of years the anti-angiogenesis drugs looking as if they’re interesting, looking as if they’re prolonging survival, that’s quite good fun and useful for patients who are platinum resistant. At this meeting we have cedirumab, which is an anti-angiogenesis drug, being tested with olaparib, which is a PARP inhibitor, versus olaparib alone and seeing an effect which was positive for patients’ progression free survival for the combination versus the solo.

In colorectal cancer, another one of the big ones, not a great deal of news, a number of drugs which are looking as if they have some activity down the line. But an important clarification for oncologists who see a lot of patients with colorectal cancer, we’ve agreed that FOLFIRI and FOLFOX don’t seem to make too much difference which one you go for, you choose your combination according to the patient’s status and other comorbidities. Now it seems that it doesn’t matter whether you go for bevacizumab or cetuximab; in a randomised trial they both look the same. So you choose the one, or you choose with your patient which one of these drugs will give you the best side effect profile according to existing comorbidities like existing hypertension etc.

So that’s breast and that’s prostate and ovary and lung. And now some of the smaller cancers but in these small cancers, as you’ll hear, some really important steps forward.

In the less frequent cancers there have been some dramatic results presented at this meeting today. Two years ago at ASCO it was melanoma all over the headlines, well melanoma is certainly hitting the newspapers again in this year. A couple of years back it was ipilimumab and this year it’s the PD1 or the PDL1 inhibitors and they really are very, very exciting indeed. Stick, first of all, with ipilimumab; interestingly that having shown such spectacular success in metastatic melanoma it has been moved up front as an adjuvant in resectable melanoma and it looks as if it’s a good idea, it looks as if there’s some significant, at least, progression free survival data coming through. Then turn to the new PD1 inhibitors and there’s one with a ridiculously long name, pembrolizumab or something like that, but its original number was MK3475. The new name, I think, was just announced at ASCO and this drug is a single agent showing really impressive responses, 40, 50, 60% responses, in advanced metastatic melanoma. Ahead of it is nivolumab which showed the same sort of profile, maybe not quite so impressive, but impressive enough to be put into combination with ipilimumab and that looks very promising indeed which confirms the notion that these two sets of drugs, the ipilimumab category of drugs and the PD1 checkpoint inhibitor drugs, are indeed hitting different targets and therefore maybe complimentary in combination. That looks like what it is, we’re getting not just good response rates, above the 50%, but we’re getting durable response rates out to a couple of years and beyond that. So that’s really good news for melanoma.

Then take the leukaemia situation, an interesting couple of papers that hit the plenary sessions, one on CLL where ibrutinib, which is a Bruton’s tyrosine kinase inhibitor, has been shown to be better than standard treatment in aggressive relapsed resistant CLL.

In another less common disease, but very similar in terms of the pathogenesis and it may be that one leads to the other, is mantle cell lymphoma and in mantle cell lymphoma there’s been an interesting change of cocktails, if you like, reflecting the fact that bortezomib is, indeed, a very effective drug and quite a safe drug in these patients who have a median age of 70-ish. This was a randomised trial which compared the standard, which is rituximab-CHOP, with a cocktail which is switching the vincristine for bortezomib and showing superiority for the bortezomib regime. Good news for mantle cell lymphoma patients, although they’re few in number, and it’s quite likely that this sort of new cocktail will go on to show efficacy in the other B-lymphocyte lymphoid neoplasms which, of course, are more numerous.

Lastly a very rare cancer, at least in the medical oncology practice, and that’s thyroid cancer, frequently taken care of by the radiation medicine divisions or nuclear medicine divisions in hospitals because, of course, most of these thyroid cancers, even when metastatic, respond very nicely to injections of radioactive iodine. For patients who are in the minority who are resistant to radio-iodine or to the subsequent drugs which are mostly not very effective, cytotoxic drugs in particular, there is a new drug which was reported by the Gustave Roussy team in France and this is lenvatinib. This was a randomised trial of lenvatinib versus standard care and there was a dramatic improvement in all the outcomes measured, response rates over the 50% mark versus 5-10% mark and progression free survival 2-3 years versus less than six months. So although it’s a small niche cancer it’s very important that this targeted drug can indeed produce quite impressive anti-cancer responses.

For the rest of ASCO, and for those of us not practising in the United States, there was a lot of political stuff about funding and about guidelines and so on. But even for those of us who were not involved with the domestic discussions this was a very rewarding ASCO and we look forward very much to 2015 when a number of these really exciting antibodies in particular and small molecules will be shown, I suspect, to produce serious survival improvements for patients with cancer.

Thanks very much indeed.