ESMO 2016

Editor's ESMO 2016 roundup

Prof Gordon McVie - Editor in Chief, ecancer

Welcome to ecancer.tv at Copenhagen, the ESMO meeting. They say up to 20,000 people are here, it’s lovely to be in Copenhagen. I’m just going to pick up some of the positive highlights, they’re in breast cancer, non-small cell lung cancer, bladder cancer and kidney cancer. You won’t be surprised, having read your daily newspapers, that the immuno-oncology drugs are all over the place and they’re really making a continued big impact. Some of the data here is really important, for instance the first trial, an EORTC melanoma trial with ipilimumab, we’re now seeing continued responses out five years after the study started.

It prolonged overall survival, distant metastasis free survival and relapse free survival. It was                       consistent  across all survival endpoints and in absolute terms the consistency is 11% for overall                 survival, 11% for distant metastasis free survival and 11% for relapse free survival.
                                                  Alexander Eggermont – Institut Gustave Roussy

The costs in terms of adverse effects are really unchanged since the first report of a significant spread of the curves a couple of years ago. There are no new side effects, no late toxicity. So really that’s quite important.

Then we have two trials on bladder cancer, metastatic bladder cancer, notoriously resistant to conventional therapy and two of the PD-L1 checkpoint inhibitors have been tested in two phase II studies.

What we observed in the first 100 patients was that the objective response rate was 24% and the                  complete response rate was 6%. Coupled with the data from atezolizumab, what we are seeing is                that the responses are very similar and that these do make a strong argument for first line                            immunotherapy, at least in a subset of patients with metastatic urothelial cancer  
                                                  Arjun Balar – NYU Langone Medical Center

Next we have a breast cancer phase III trial showing superiority of ribociclib when it’s added to letrozole.

Ribociclib was well tolerated, patients had a statistically significant and a clinically meaningful increase in progression free survival compared to letrozole plus placebo or letrozole alone.
                                                  Gabriel Hortobagyi – Copenhagen University Hospital

Advanced lung cancer has really been resistant to everything, short term remissions with platinums and taxanes but now again we’re seeing nice responses with either substitution or addition of immune oncological drugs. Atezolizumab is a new kid on the block in lung cancer, we’ve already got two PD-L1s approved by the FDA and this one is an interesting drug. It has been tested head to head with docetaxel in 1,200 patients.

There was a strong survival benefit for the atezolizumab compared to docetaxel. The median                        overall survival goes up from 9.6 months for the docetaxel to 13.8 months for the atezolizumab                   arm.    
                                                  Fabrice Barlesi – Hôpital Nord

That’s really quite important because the side effects are less with that drug than with conventional docetaxel.

In patients who have got platinum resistant non-small cell lung cancer another drug, pembrolizumab, is showing good quality data and in a trial of one-to-one pembrolizumab versus chemotherapy pembrolizumab came out best with a crossover where forty-odd percent of the patients who were on the placebo study went over onto the pembrolizumab.

Of the median progression free survival from 6 up to 10.3 months corresponding to a hazard ratio               of 0.5 and corresponding to a p-value of below 0.001.
                                                 Martin Reck – Lung Clinic, Grosshansdorf

So we don’t have an overall survival advantage for that drug but we do have a clear progression free survival advantage. So, yet again, in a common cancer, difficult to treat, new data suggesting new optimism about using an immuno-oncological drug.

The same drug, pembrolizumab, in combinations, the well-known couplet of carboplatin and pemetrexed, non-small cell lung cancer, metastatic, head to head, one antibody versus two chemotherapeutic agents and the antibody is looking superior.

The response rate was nearly double, 55% compared to 28% for the control group, and we saw                   more than a four month improvement in median progression free survival from 8.9 months to 13                 months for the pembrolizumab combination.
                                                 Corey Langer – University of Pennsylvania

We’re all too familiar with the side effects of pemetrexed plus carboplatin. The antibody is less aggressive and the results look as if they’re being maintained out beyond a couple of years. Very, very exciting and very interesting indeed.

ALK lung cancer is rare, it’s only 4-5% and we know that crizotinib is a very good drug indeed but what happens when crizotinib fails? Ceritinib is reported today as being a rescue agent which is very positive news and it’s looking probably as good as crizotinib.

In the experimental arm ceritinib was statistically superior to the control arm represented by                     cytotoxic chemotherapy. The hazard ratio was highly clinically significant because the hazard                     ratio was 0.49 and the target hazard ratio, according to the study design, was 0.60 so the real                       hazard ratio was far below.                                                                                                                                                                  Giorgio Scagliotti - University of Torino
 

Some people are saying, ‘Well we’re now going to use ceritinib up front’ or challenge crizotinib for the first line therapy place. That’s certainly going to have to be done because the data on ceritinib are most encouraging.

From a rare kind of lung cancer we can go onto cabozantinib in renal cancer, also a cancer with an established first line treatment and, again, what do you do after sunitinib? There are one or two options out there, particularly VEGF attacking drugs. Cabozantinib is one of those, it’s a tyrosine kinase and it does go for VEGF, that’s vascular endothelial growth factor, but it also seems to have activity on MET and on AXL.

Cabozantinib provided superior progression free survival as well as response rate over sunitinib                  with a similar adverse event profile.

                                                  Toni Choueiri – Dana Farber Cancer Institute

So, again, nice data in patients who are resistant to sunitinib and it’s looking as if this new drug will be challenging sunitinib for the up-front place.

Ovarian cancer has been a target for the PARP inhibitors for a couple of years now and now we’ve got some really nice data on niraparib, one of the PARP inhibitors.

Niraparib significantly improves PFS in patients with platinum sensitive recurrent ovarian cancer               in the whole population.
                                                 Mansoor Raza Mirza – Copenhagen University Hospital

The median progression free survival was 21 months versus 5 months in the placebo group so that’s a pretty big impact. For those who are mutation free, neither BRCA1 nor 2 mutations, there was still an advantage for using this new PARP inhibitor but it was less and it looks as if another marker might have emerged from this study which is HRD, which stands for homologous recombination DNA.

So really a harvest of new drugs strong enough in the second line treatment to be challenging for first line investigation and I’m sure over the next six months, probably at ASCO next year, we’ll be getting some mature data on some of the randomised phase II and phase III trials that are coming along. So really good news across the board: lung, breast, ovary, kidney, bladder and ALK positive non-small cell lung cancer. So stay tuned to ecancer.tv and we’ll keep you abreast of progress.