Prof Gordon McVie – Kings College London, London, UK and Founding Editor, ecancer
Will Davies - ecancer

Hello, and welcome to the ecancer round-up for ESMO 2018. I’m Will Davies, the ecancer reporter and joining me for your 47th ESMO, I believe it is, Professor Gordon McVie.

Thanks very much. Every year gets a little bit better, small steps forward; no breakthroughs, no massive headlines again this year but some nice little increments so that’s good.

Let’s start with some of the news from today in head and neck cancers. The KEYNOTE-048 trial for first line pembrolizumab for relapsed squamous cell carcinoma – pembrolizumab in head and neck cancer works in this population.

Yes, that’s the good news. Head and neck squamous cell particularly is a really tough cancer, very resistant to anything you throw at it, especially after patients have radiation therapy plus or minus the platinum or something like that. So this is good, this is one of your nice steps forward.

By way of comparison to the adverse events seen in the EXTREME, the aptly named EXTREME, chemo arm.

Yes, rituximab in patients with HPV positive head and neck cancers did not do well, I think that’s probably the best thing said about it. A bit too much toxicity to be taken on to the next round.

So we’ve got the good news and the bad news out of head and neck there but on to more good news again. From the breast cancer sessions we’ve heard fantastic stuff coming from all kinds of corners, starting with the first immune success in the IMpassion130 trial presented by Professor Schmid.

Yes, this is a huge trial, about 900 patients or something. Paclitaxel with a nab on the end of it, together with atezolizumab and they’re looking at breast cancer failed several lines down the way. The criteria for the PD-L1 targeted drug was having PD-L1 staining, I have to say, and I’ll say this later on, there’s still quite a bit of doubt about whether this is a good biomarker or not. But there is a survival difference in these two arms, it looks like 7.2 months for the combination versus 5.5 months for the chemotherapy. As you say, a first little step forward in a randomised trial for immunotherapy.

Once you’ve got the first success in PD-1 therapy it seems like there’s a lot of attention, a lot of interest in trying to get everyone else’s PD-1 drugs into the space and see what can be done. Hopefully that translates into benefit for the patients at the end of the day as well.

It’s not for want of trying because every pharma company is trying to get an immuno-oncology drug and I was told the last count there are about 400 trials going on globally on the immuno-oncology approach right across the disease spectrum. Because that’s one of the exciting things, this isn’t just a disease specific approach, this is global and that’s good news.

Congratulations again to Professor Schmid and to all of the patients being treated for the gains that they are making. Then another headline from the breast cancer news coming out of this year’s ESMO with the success with the PALOMA-3 trial of a CDK in HER2 negative HR positive disease.

This has been signalled last year and also a little bit at ASCO but basically palbociclib is growing roots and the database is growing and it’s challenging now to be looked at in first line or close to first line treatment. The target is interesting and there’s no competition for that target at the moment but there will be other CDK4/6 inhibitors coming along. At the moment palbociclib is out in front and good data.

So they’re whittling down the ways in which CDKs might not be suitable for someone to a very small degree in that anyone with a breast cancer and many ovarian cancers should be considering CDK treatment at some point in their progression through the disease.

I think we should be saying that is the optimal approach now for all cancers. If there’s a biomarker which has got a link to a target oriented drug then that’s the way you should be going and this is a good example of it.

One last breast story coming from the second line therapy for relapsed patients using an HDAC inhibitor called chidamide.

Yes, HDACs have had a rough time, frankly, mostly due to excess toxicity and not a lot of response. On this occasion chidamide has actually produced a response, a 20% response, which is quite a tough call in heavily pre-treated patients with breast cancer. But again it’s dogged by side effects and about 20% of the side effects were seriously adverse. But it’s a blink of hope for HDAC as another target, not on the genome but next to it on the epigenome.

Maybe the summary for breast cancer news, then, is that watch this space. We’ve got the success with immunotherapy, CDKs gaining more and more of a foothold, like you say, the HDAC news and these small steps are going to culminate in some very large leaps hopefully for patient survival and the way that they can tolerate the treatment with reference to the HDAC inhibitors. We can see that coming, this might just be the first part of that story.

Yes, I think the next two or three years and that will be sorted and we’ll be on to the next set of questions.

On to the next set of questions then. Some news from the lung cancer space – erlotinib surpassing gemcitabine in a phase II trial. It improved overall response and progression free survival. Data out of a Chinese trial.

This is a neoadjuvant trial which I think is quite exciting because if I just go back to where the next steps might be in breast cancer I would think that’s seriously into the neoadjuvant space. There’s a lot of people doing it in small numbers at the moment and I think neoadjuvant chemotherapy, immunotherapy, immunochemotherapy, immuno-immunotherapy for breast, for lung, for colon, for ovary, that’s going to be an interesting way to really make an impact on complete remission and longer term survival. So this is a nice study showing that erlotinib is better than gemcitabine, as far as I can see, in terms of overall response rate and progression free survival in non-small cell lung.

The neoadjuvant space seems to be taken over by quite a lot of research going on in melanoma as well, we heard some of that, but let’s move on to the urothelial space. We’ve got news out of the JAVELIN trial, this has been something of a headline from this year’s conference – the improvements seen using avelumab, a PD-1 antibody again, with axitinib. Improving PFS, response rate but no overall survival data as of yet.

And this is in kidney cancer.

Yes.

This is the example I was referring to earlier where there is an improvement in progression free survival for the combination of the PD-1 combo but it doesn’t seem to tie up with the PD-L1 staining. So the biomarker has let us down. The great idea is biomarker, we’re going to get a massive response rate from those who have got the biomarker, not yet is my view.

With all of the other developments that have gone into cabozantinib, we were speaking with Toni Choueiri about that. It seems like there’s a lot of work happening in the kidney cancer space. This is an improvement in terms of sheer response rate but for figuring out who gets what when there’s still a lot of discussion happening there.

Not yet. There’s certainly no shortage of choice of new agents and new approaches in kidney cancer which is really extremely encouraging.

Then on to some news from Gustave Roussy in Paris from Professor Fizazi working in prostate cancer. Docetaxel and bendamustine on top of goserelin reducing relapse rates among adult patients.

Yes, these are prostate cancer patients and there’s always a dilemma about how much to do up front in the new idea that up front is a good idea. In the old days prostate cancer was treated solely by radiation or surgery plus or minus hormone suppression and now it looks as if… it doesn’t look as if, there is serious data that docetaxel, for kick-off, in high risk patients up front is a good idea. Here’s some more data that is taking us in the same trend.

Of course prostate cancer has been one of the main headline topics coming out of the last couple of ASCOs as well – huge gains seen across the board in this space. Your thoughts on where this research in terms of new combinations is and taking research for prostate as a whole?

In thinking again about neoadjuvant therapy, sorry to go on about it but there are some good candidates. There’s enzalutamide and abiraterone which have been terribly good in patients with later disease and they’re working their way up front and adding neoadjuvant approaches. I think probably in this instance with chemotherapy because of the data on docetaxel and data with bendamustine and docetaxel presented by Fizazi here. I think that’s going to show some good effects in the next couple of years, I would think so.

Then also good news in the ovarian cancer trials for SOLO-1 using olaparib as a maintenance therapy. Two years of treatment and then survival at three years is one of the big successes from the conference, as I can tell.

I think it’s the best data, frankly, and it certainly will have the most impact on a really rotten disease which is ovarian cancer. We rarely ever cure patients with ovarian cancer if it’s stage 2 or bigger. We get nice responses and they last for some years but then this disease comes back and it’s a real problem. That is a courageous study based on good science with the PARP inhibitors etc., but to do a placebo trial of maintenance for two years against a drug like olaparib, that took a fair bit of risk and it has paid off. This is a terrific result, the progression free survival for patients who got the placebo is 13.8 months, that hasn’t been reached yet in the olaparib group and they’re out three years on. So I think this is terrific and this is going to generate a lot more interest in ovarian cancer which, frankly, has been a little bit overlooked over the last wee while.

PARP inhibitors, alongside CDKs, is one of the treatment modalities which more data comes out year by year, like you said, with CDK gaining a foothold, gaining roots. It’s just proving to be a great treatment option for many, many patients.

Yes, I think it’s much bigger than we originally thought which was going to be useful in BRCA1 and BRCA2 mutated patients with breast cancer. Then it was BRCA less and then it was ovarian cancer, then triple negative but actually it’s probably going to be wider than that and I think it’s a good drug and there are a lot of other PARP inhibitors coming along. Yes, this is good science translated into good clinical practice, good for patients.

What we like to hear. Then also in colon cancer we’ve got the combination of checkpoint therapies in CHECKMATE-142 using both ipilimumab and nivolumab together in this trial.

Yes, I think this is great actually. The theory was going to be one works and not cross-resistant with the other therefore put them together. That was not a massive success in lung cancer which was announced a few months back, but here it seems to be paying off with big response rates up at about the 70-80% mark, quite impressive, and good overall time to progression and time to relapse. So this is one up for the immuno-oncology boys who have again had the courage to take a bit of risk – they could have had maximum toxicity, they could have additive toxicity – toxicity doesn’t seem to be massive, 16% serious toxicity, so yes, this risk paid off too. So that’s good for immuno-oncology.

I’m going to clarify, that’s in a somewhat smaller subset of patients with DNA mismatch repair deficiencies or microinstability high tumours.

Yes, this is a small subsection of colorectal cancer but it’s 5% maybe with mismatch repair, but 5% of a common cancer is good news for those patients and the whole notion of finding your mutations or the epigenetics or your proteomic errors in tumours and then going into more educated, intelligent treatment, I think that’s paid off. When ALK was uncovered in lung cancer, non-small cell lung cancer, people said, ‘Well, that’s not very interesting,’ but now after crizotinib we’ve now got two more candidates which are doing even better than crizotinib. Lung cancer is a very common cancer and this is a big step forward in non-small cell lung cancer, as it now is colorectal cancer. It’s really good, it’s a way forward. Small steps, small increments. You have to be patient.

All these small steps in personalised medicine, if there is a way to summarise the conference overall it’s that the personalised and precision techniques are being employed widely by many people across the world in many different trials and success is happening.

Yes, it’s obvious from here at the exhibition stands, there’s still precociously expensive stands around the place from the pharma companies which I’d rather see going into patient care and lower costs of medicines, but they are all looking at immuno-oncology, there are four or five companies here who have got genetic testing on tap with recommendations on the matching to drugs. I think that’s showing the way that it’s going to go and, yes, I’m very pleased with it. It’s only my 47th ESMO but it’s certainly the brightest in terms of patient care overall, taking the last few years into account. Very positive.

Speaking of better ways to spend one’s money, the biosimilar symposium from this year’s ESMO leads into a lot of stuff – ecancer has the educational module out about what biosimilars are and how they can be used. Based on survey data that has been discussed by Professor Vulto and Professor Luftner, there is a need for education and understanding about what biosimilars are.

Yes, they’re identical drugs or they’re near-identical drugs and they’re just as good as the originals. The likely savings for the health service in Europe, which at the moment is about 20 billion, will be about 2 billion so it’s a 10% reduction in going into a relationship of trust with these drugs. Just because they’re called biosimilar doesn’t mean to say that they’re not going to work. They do work and, as you say, ecancer has just put up online an excellent educational programme for those clinicians out there who actually haven’t come across biosimilars yet but they maybe should be because they’re going to cut down their health budget.

If it costs less and does the same then there’s very few reasons to not think it’s a good idea.

I can’t think of one.

Well that leaves us with only the awards to discuss. The award for Women for Oncology went to AACR President Margaret Foti at ESMO this year. Can you tell us what the award means in the field?

Well, anybody who has dabbled, even dabbled, in cancer research will know Marge Foti. She has been the pioneer in communication of research results via not just Cancer Research, which was the AACR big signal journal, but I think she’s spawned fifteen or sixteen more journals as the whole area of cancer research got split into little silos. She is just an absolute giant in the field of cancer research; she is a superlative leader, she’s built up AACR, she has had an influence right across the world and I cannot think of a single man who can outmatch her, never mind woman, in getting the women’s award. If I were on board, the most prominent person in the area of cancer research in terms of what we do at ecancer, also disseminating it and getting the word out there, then Marge Foti would get my vote every time and she’s a lovely woman.

So that’s all from us at ESMO this year, we’ll be back sometime soon with news from conferences around the world. We look forward to speaking with you then.