Friday morning opening Melanoma session started with Cancer Immunotherapy: What Every Oncologist Should Know (or in the case of a patient what you HOPE your oncologist knows!!)
After a basic introduction to Immuno system and how it works called back to basics there was a presentation on Cancer Vaccines can we make them work these are not to be mistaken with preventative vaccine these are vaccine to actual disease.
Main Topic; Checkpoint Blockers don’t work because of lack of T Cell proliferation, Vaccine can increase T Cell activity if you find the right *Epitope* (is part of an antigen recognised by immune system by antibodies such as B it T cells the epitope is the specific piece of the antigen to which the antibody binds) (Wikipedia)
Chemo + Vaccine delivered at the right MDSC level (measure in blood) can be effective but also a checkpoint inhibitors + vaccine can boost T Cell response. (Cornelis Melief Leiden Netherlands)
T Cell Therapy For Whom and When?
Patients care is paramount all patients WILL suffer grade 3-4 Toxicity AE
Patients are usually heavily pre-treated 50-70% response rate with ORR 42%
Patients need sufficient organ function, No brain mets or max 1-2 small, No other chronic illnesses
Response rate is not effected by Braf status or LDH levels, for patients with rapid progression disease waiting for Til transplant Braf inhibitor may be used 1 week before treatment to stabilise side effects of disease, there is a long term clinical benefit of Til transplant after Braf. Resection of isolated tumour progression is also effective and patients can still be long term survivor. Selected patients should be offered TILs treatment they can see long term complete response. (Inge Marie Svane, Herlev Denmark)
*it must be remembered investment in TILs research is suffering because it is not commercially attractive to Pharma industry*
Afternoon Session: Adapting Trials to Tumour Biology;Shooting at a Moving Target
NO TUMOUR NO TRIAL, NO LONGER APPLIES, liquid biopsy can provide the information necessary to participate!
Is this really true yet, in my opinion NO as according to Keith Flaherty, Boston, the diagnostic structures are not in place yet for many countries, so the solution maybe large scale Basket Trials.
Modulating responses using CtDNA: liquid biopsies /Tumour Circulating DNA, will be valuable for early diagnosis of cancer and to asses if a patient needs more treatment after surgery, it also allows a patient to be very closely monitored during treatment. Of course the ability of the tumour environment to evolve remains a challenge and rechallenge therapy maybe not much success but learning and analysis of more information possibly on intermittent use of treatment are beneficial from liquid biopsies. (Alberto Bardelli, Italy)
Special Symposium: Optimal Combination and Sequencing Strategies in Melanoma
Combo of Ipi + targeted could in theory get favourable results
Concurrent use of Vemurafenib + Ipi might not be tolerated because toxicity problem in liver
Phase I data Dabrafenib + Ipi with or without Trametinib do not cause liver toxicity problems
Triple combo Ipi Dabrafenib + Trametinib is not feasible due to increased gastric problem (bowel perforations)
Sequenced use of Ipi and targeted might be a better treatment path (Paolo Ascierto, Italy)
Caroline Robert Villejuif France
Opens her presentation the Rationale for Sequencing with a statement about the problem faced by patients who are taking targeted therapies knowing they will eventually progress and should they switch therapy before progression. There are some theories to support a switch but no evidence as yet if it is right to do so, in long term OS prospect for patients, however some physicians and patients are agreeing to do so without any guidelines. They may base decision on theory it is better to switch before mechanism of resistance is present in the cells. There is unfortunately no data being collected about those who have switched shared for the information of future guidelines. While they all agreed I had a good point in asking Ms Robert, the answer is for patients unfortunately more trials, to collect clean data, unfortunately some patients won’t have time to wait for answers to that question, the decision will be preempted by progression. They did ask audience to please submit any data they have on patients they may have already switched so hopefully something will come of my question or some eager young Onc take it on as a project.
Can Biomarkers help make the decision?
Yes they are an important tool in the decision making process, but they are still having a lot to learn and the facilities to test must also be available, it must also be explained to patients what these Biomarkers mean to them in terms of accessing treatment, this is really about personalised treatment options, it is better for patients as time isn’t wasted giving ineffective treatment, over treatment is a problem it is always best to access the most efficient treatment for patients first line if possible, this may include new combination like triple treatments checkpoint inhibitors, Mek inhibitor and anti PD1 all given at same time or sequence closely together there are new trials coming on stream for these but unfortunately for some patients already in treatment they cannot access these as they are sometimes pretreated or have exclusion criteria that they fail or trial is not available in their country
Antoni Ribas Los Angeles,
A closer look at the current guidelines on sequencing and combinations
Paul Lorigan, Manchester
How can we predict which patients will have progression and when it will begin at the moment guidelines are also being written not based on Clinical need but on availability of Treatment!!
Advantages of Guidelines for Metastatic Melanoma
Address inequalities in access and standard of care
Used to support decision making
Can be used by patients and incorporated into Patient decision aid (PDA)
Used as a basis for outcomes measurement
Disadvantages for Guidelines
Optimal multimodality treatment of brain metastasis
Combining SRS with immunotherapy or targeted therapies
Combining WBRT with immunotherapy or targeted therapies