I know some of you might think this is a bit slow off the mark and I must apologise for that. September turned into one of the busiest months I had all year. It’s taken me a while, but course we must remember that much of the information that comes from large conferences is for the future because it is in essence research.
It is gathering the evidence through clinical trials that will shape the treatments of tomorrow. So me being a couple of weeks behind won’t upset the apple cart too much!
Some of the biggleist (is that an offical word now) groundbreaking results were again this year to be found in Melanoma. This time though the difference was it is in the Adjuvant setting (preventative treatment for reoccurrence). This is an area where there has been an enormous unmet need for patients and a huge market for Pharma. It is a race to get treatments on the market at the moment so the results were eagerly anticipated, we knew there would be some big announcements.
If you are already at high risk of recurrence stage lll, this information unfortunately is a little too late to join, unless you were lucky enough to get on one of the trials already running in another country and on the right treatment arm of that trial. These trials have very strict critera for recruitment and treatment would have to commence in a specific time frame after surgery.
These are just trials and no one can know from the outset if the new treatment is going to be superior to the old standard of care. It is a game of chance where you end up, but for future patients, today’s trial participants may be paving the way for the possible best treatment for everyone not just those who get randomized to the right arm.
The two trials which also published results the week of ESMO 17 were the Adjuvant use of targeted therapies Braf/Mek inhibitors and the use of Nivo immunotherapy.
Lets take a look at the Targeted therapies first, these have been very successful in treating patients with metastatic disease, so there was every hope that they would show similar results in the earlier stage patient.
The trial which is still ongoing is called the COMBI-AD and is at present in phase 3. For patients who had their melanoma removed surgically and then received Dabrafenib and Trametinib it was reported to provide a 53% lower risk for 3 years over the placebo arm. The efficacy (the ability to produce a desired or intended result) and how it was tolerated by patients was seen as an important step forward in treatment of stage lll melanoma for BRAF positive patients, said lead trial investigator – Prof Axel Hauschild. He added these unprecedented results confirm a targeted therapy combination has the potential to transform the standard of care in the melanoma adjuvant setting.
The second trial is called Checkmate 238 and this was the study of Adjuvant Nivolumab Vs Adjuvant Ipilimumab immunotherapy. You might recall an earlier trial EORTC 18071 of adjuvant Ipi had been presented at last years ESMO conference and whilst controversial because of toxicity it had shown benefit. On this new trial 906 patients participated with 453 randomized to each arm of the trial. At 12 months the difference in each arm was relapse free surivial 70% Nivo and 60% for Ipi. When it was again followed up at 18 months the difference started to open up with 66% of patients relapse free on Nivo versus 53% on Ipi. Also Nivo came out a clear winner on toxicity with only 14% having grade 3/4 adverse effects compared to 42% of patients on the Ipi arm. The trial also showed benefit favouring the Nivo arm for patients regardless of PDL-1 expression and although patients who were BRAF wild type did slightly better, those who were BRAF positive also benefited more on the Nivo arm.
So we now have two definite candidates for Adjuvant treatment in the future of course the FDA will require further long-term survival follow-up data before deciding on their approval.
We also had follow-up results from the Checkmate 067 trial for stage 4 metastatic disease which showed three-year survival rates were 52% with Nivo mono Vs 34% Ipi mono and 58% for combination of Ipi/Nivo. These are game changing figures when you consider majority of stage 4 patients would not have survived past 6-12 months historically.
There is however the doubling of serious side effects to be considered when deciding on the combination treatment but we have also recently seen its positive results on patients with Brain metastasis in the Checkmate 204 trial.
Another thing to put on watch for future developments was presented by Prof Peeper from the Dutch Cancer Institute it is the development of AXL inhibitors which could benefit patients becoming resistant to BRAF/Mek inhibitors an ongoing problem for many patients that sees them progressing whilst taking targeted therapies. We will be following this research with keen interest. A FIM or first in man phase 1 trial has commenced to establish safety of the new treatment.
There was also the birth of a new Mab called relatlimab at ESMO 17 as we heard about initial results on patients who have relapsed on Anti Pd1/Pd-L1 treatment treated with this in combination with Nivo. Half of all patients treated and two-thirds of those patients with LAG-3–positive tumors benefited it seemed patients without the BRAF positive mutation did better. Unfortunately too many patients find themselves in the position of having already failed Targeted therapy and immunotherapy at the end of the treatment pathway this trial offers a glimmer of hope in a grim situation and such is the desperation for new options I have heard there is a waiting list to get screened for this trial in a European trial centre that cannot accept any more patients. Research very sadly does not move as quickly as necessary for us patients it is a long slow process to identify a target, find lead molecules that might be developed into drugs and then go through the regulatory and trials process to ensure it’s safe to use and it is effective as a treatment.
Also on the menu so to speak was the subject of fecal transplants (put down that Poo, this is not a DIY job) this research has been ongoing at University of Texas MD Anderson Cancer Centre. It is suggested that gut microbiome may influence your response to immunotherapy treatment. Something that may change the health of your gut microbiome is using antibiotics in the month prior to immunotherapy treatment (study by Gustave Roussy Cancer Institute Lisa Derosa MD). But of course it is not recommended to forego treatment for an infection if needed. It is a hot topic of research at the moment and we await further results on this. The gut bacteria that is being examined is very particular and not of the type to be found in your morning yogurt drink, it’s also not a good idea to rush off to the health food shop for supplements without first contacting your consultant if you’re in treatment as many over the counter medications can cause adverse drug interactions.
So there you have it a small summary of some of the most groundbreaking research in Melanoma at present, it gives great hope for the future that these treatments will save and extend many more lives beyond the realms of what we think is possible the future is bright the future could be Poo!!!