McVie, J. Gordon MD
J. GORDON MCVIE, MD
At this year's ASCO Annual Meeting, I was presented with a yellow ribbon that said “35 year member,” something that produced mixed feelings, but does give me the authority to say that this was a good ASCO! We've had some less exciting ones in the past, but this was one that really impressed.
Let's start with the two hormone-sensitive cancers—the big ones, specifically. I think we may have a change of practice here because a big Phase III study, E3805 from Dana Farber, showed that in adjuvant treatment of prostate cancer, docetaxel plus the usual treatment, androgen-deprivation therapy (ADT), was better than ADT—and that it is 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 make some changes in the way that urologists 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 (CRPC). The first one was abiraterone, and the data continues to be good, with good long-term response rates, and that is really good news.
The second was enzalutamide, which was the other drug that hit the headlines last year at ASCO and also continues to show good data.
However, neither of them are curative, and it's not clear which one you should use first. What seemed to emerge was that neither is good in second line; they're each better in first line. Inevitably there was a combination study of abiraterone plus enzalutamide, which was really exciting. It wasn't a big study, and it wasn't a randomized study, but it did show that this was an exciting way forward in the treatment of CRPC.
Now on to 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, that 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 found to be superior to tamoxifen. Now that is important if you're in Western countries where you can afford exemestane, but it should be noted that for a lot of the world tamoxifen is still the gold standard and it looks as if 10 years of tamoxifen is better than a lesser duration.
On the topic of ovarian suppression for breast cancer, LHRH analogue suppression of the ovaries with goserelin showed a really quite encouraging effect. It was seen to protect the ovaries in young, premenopausal women who received chemotherapy, and I think this is also on its way to becoming a standard of therapy.
After the hormone-sensitive cancers, let's deal with the other big one: lung cancer. There, to my astonishment, was small-cell lung cancer. We've heard very little about small-cell lung cancer in the last 20 years, but here we had a demonstration that even in extensive disease, irradiating the primary tumour was a good idea. It's the same in other cancers: get the bulk disease down and you can have an effect even on distant metastases.
There was also an interesting paper suggesting that primary cranial irradiation (PCI), was not necessary in small-cell lung cancer in cases where there wasn't a visible metastasis on an MRI scan. This is good news, telling us that instead of giving everybody the toxicity of PCI—assuming they have achieved some sort of remission with chemotherapy and radiotherapy—that you can check the brain status with MRI, and if it is negative, then there is no need to go on with prophylactic cranial irradiation.
In non-small cell lung cancer, there were a couple of important findings: The first was in stage 2B and stage 3 cancers when treated with chemoradiation: There has been a trend to give adjuvant chemotherapy, but new data from a randomized trial suggests that is not actually adding anything except toxicity.
Then there are a number of drugs 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.
However in the REVEL Phase III study, 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.
Over the last couple of years in ovarian cancer we have seen anti-angiogenesis drugs looking interesting. Their ability to prolong survival has been good news, especially for platinum-resistant patients.
At this meeting we saw the anti-angiogenesis drug cediranib being tested with the PARP-inhibitor olaparib versus olaparib alone. A positive effect was seen on progression-free survival for the combination versus the solo drug.
In colorectal cancer, another one of the big ones, there was not a great deal of news, although a number of drugs look like they may have some activity down the line.
There was, however, an important clarification for oncologists who see a lot of patients with colorectal cancer. We have agreed that it doesn't seem to make much difference if you use FOLFIRI or FOLFOX—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 randomized trial they both look the same. So you—and your patient—choose which one of these drugs will give the best side effects profile according to existing comorbidities like existing hypertension, etc.
In the less-frequent cancers, there were some dramatic results presented. Two years ago at ASCO it was melanoma all over the headlines, and melanoma certainly hit the newspapers again this year.
A couple of years back it was ipilimumab and this year it's the PD-1 or the PD-L1 inhibitors, and they really are very, very exciting indeed.
As ipilimumab showed such spectacular success in metastatic melanoma it has since been moved upfront as an adjuvant in resectable melanoma. It looks to be a good idea with some significant progression-free survival data coming through.
Then the new PD-1 inhibitors: Pembrolizumab (MK-3475) is a single agent showing a 34 percent response rate in advanced metastatic melanoma, with an estimated one-year survival rate of 69 percent, and median overall survival duration not reached.
The estimated one-year survival rate was 74 percent in patients not previously treated with ipilimumab and 65 percent in patients who received prior ipilimumab therapy.
Also of note are long-term follow-up results from a Phase I study of nivolumab showing that concurrent treatment with ipilimumab produces an unprecedented median survival of roughly 40 months for advanced melanoma. That looks very promising and confirms the notion that these two sets of drugs are indeed hitting different targets, and therefore may be complementary in combination.
So we're not just getting good response rates—above 50 percent—we are also getting durable response rates out to a couple of years and beyond that: Really good news for melanoma patients.
In leukemia we saw an interesting paper on CLL hit the plenary sessions, where ibrutinib (a Bruton's tyrosine kinase inhibitor), was shown to be better than standard treatment in aggressive relapsed resistant CLL: The Phase III RESONATE study saw ibrutinib associated with an 80 percent lower risk of disease progression and a 57 percent lower risk of dying compared with ofatumumab.
Mantle cell lymphoma is another less-common disease, with a very similar pathogenesis to CLL, where we have seen an interesting change of cocktails, reflecting that bortezomib is indeed both an effective and a safe drug in patients who have a median age of about 70.
A randomized trial compared the standard rituximab-CHOP with a cocktail switching the vincristine for bortezomib and showing superiority for the bortezomib regime. This is good news for mantle cell lymphoma patients, and it is 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 medical oncology practice: thyroid cancer. These cancers are frequently taken care of by the radiation or nuclear medicine divisions in hospitals because most, even when metastatic, respond very nicely to injections of radioactive iodine. For the minority of patients who are resistant to radioiodine or to the subsequent drugs which are mostly not very effective—cytotoxic drugs in particular—there is a new hope.
Data was reported by the Institute Gustave Roussy team in France, following a randomized trial of lenvatinib versus standard care. There was dramatic improvement in all the outcomes measured; a response rate of 65 percent versus five to 10 percent, and progression-free survival of two to three years versus less than five months. So although this is a small-niche cancer, it is very important that this targeted drug can produce quite impressive anti-cancer responses.
Looking toward 2015
For the rest of ASCO, and for those of us not practicing in the United States, there was a lot of political talk about funding and 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 I very much look forward to 2015 when a number of these really exciting antibodies and small molecules will be shown, I suspect, to produce serious survival improvements for patients with cancer.