My Malignant Melanoma

The Ipilimumab Vemurafenib Combo trial we thought would never happen is on the starting blocks...

Labels: Clinical, ipilimumab, PLX4032, Trial, vemurafenib, yervoy

Phase III trial results are in for PLX4032, and they are looking pretty good:  In the study, the risk of death was reduced by 63 percent for people who received vemurafenib compared to those who received chemotherapy. In addition, vemurafenib significantly reduced the risk of the disease getting worse by 74 percent compared to chemotherapy.

Labels: Clinical, PLX4032, Trial, vemurafenib

Update on the top new MM treatments:

Allovectin-7

Immune system booster, Phase 3 trial had positive results


Oblimersen

Gene therapy, Phase 1 trial results just in- showed no responses at planned dosage


Ipilimumab

Antibody targeting CTLA-4-this is the only drug so far shown to prolong life, available both via open UK trials and for compassionate use


OncoVEX

A modified virus carrying a helpful gene, looks promising so far, there is an open UK Phase 3 Trial.

PLX4032

BRAF inhibitor - early trials showed high response rates but it seems that these responses may be short-lived, supporting the anecdotal reports which have been circulating on cancer patients' boards.

Did I say 5? Let's have a sixth/seventh- Glaxo's "me too" B-RAF and MEK inhibitors, presently in Phase 3 Trials.


Talking of MEK inhibitiors, whatever happened to AZD6244? There seems to be an open phase II trial, but no results as yet (MEK inhibitors work on a different link in the chain which B-RAF lies on, and similarly require B-RAF mutant tumours to work)

It might be that combination therapy with two of these agents would be more than twice as good as any on their own, but that would mean drugs companies cooperating instead of competing. Here's an occasion where we might wish the quacks' supposed "cancer conspiracy" were true, and drug companies really did act in concert.

Update- the combination trial is happening.

Labels: allovectin, AZD6244, BRAF, GSK212, GSK436, oblimersen.ipilimumab, oncovex, PLX4032

Someone asked me today on behalf of a mother with MM if she might have transmitted the B-RAF mutation to her kids. Short story- nope.

Longer explanation:

In order for a cancer to spread, a number of the things which prevent uncontrolled growth in normal cells have to go wrong. There are things which repair damage to DNA, limit the number of times a cell can divide, things which cause cells to suicide if they are defective, things which make the immune system kill cells, and so on.

All cancer cells have to have a range of these faults to progress even to a stage 0 cancer. You can be born with faults inherited from your parents that help things along like BRCA, you can pick them up from the action of viruses as in cervical cancer, or from the effect of radiation on DNA as is believed to be the case with the B-RAF mutation, and so on. More commonly, it is thought that a number of these things come together to make cancer.They sequenced MM tumours quite recently, and there were thousands of mutations.

We all have the B-RAF gene, which essentially acts as a check on cell growth. The mutant B-RAF gene's ineffectiveness takes the brakes off cell growth. It exists only in the cancer cells themselves. Blocking this effect is how the B-RAF drugs work. The mutant form is not likely to be in a person with MM's egg or sperm cells, and if it were, there are in any case processes which kill any sex cells with mutations. You don't pass on the mutation.

There is evidence of a familial form of MM, known as dysplastic naevus syndrome, but the suspect gene there is called p16, and the evidence is nowhere near as strong as it is for BRCA- they think other (presently unidentified) genes are involved. Only around 10% of MM has this suspected basis, and those affected have a 50% risk of MM by age 50.

Labels: BRAF, mutation, PLX4032

There has been internet chat about the emergence of resistance to the new BRAF drugs for a while-they are working on it.

Labels: Melanoma, PLX4032, resistance

I heard on Radio 4 this morning PLX4032 being described by a reporter as a penicillin moment for MM, but Sir Mark Walport was on hand to more measuredly point out that we need to balance hope with hype, that these drugs are not curative, have side-effects, and so on.


Less measuredly, an attempt was made today to comment on my Tulio Simoncini post by someone who considered David Icke's website a definitive source of medical information. That's as much as I need to say about that, really.

Labels: PLX4032, Trial

I hear a rumour from fellow patients that GSK's "me-too" BRAF inhibitor is better than PLX4032. It seem that this is partly because of the account given by this MM patient as to the lack of a complete cure given by PLX4032.

I have heard a few other anecdotal accounts from patients on BRAF trials of this nature, but these do not contradict the previous trials at all. Only a very few people in the initial trials got a complete response. Whilst overall response was way higher than for the gold standard DTIC, this is a promising cancer drug. The very best cancer drugs we have for any cancer cure a tiny fraction, and give others a bit more time, ideally with a reasonable quality of life.

Back when I was diagnosed there was just DTIC, with its 15% response rate, and no chance of a cure. Now we may have a number of drugs with up to a 60% response rate and a small chance of a cure. Progress has seemingly been made.

We can't tell a thing from internet anecdotes in the meantime, other than the drugs aren't a complete bust so far. I can remember some promising-looking drugs which anecdotes made clear in short order were not going to hit the mark.

Labels: BRAF, GSK, PLX4032

There's a paper in the British Journal of Cancer showing success in detecting BRAF mutations via blood samples instead of tumour biopsies.

The presence of these mutations is the basis for treatment with PLX4032, as well as the drug in this trial, AZD6244, though the two drugs work in different ways.

I see there is an open clinical trial of AZD6244 in Oxford, and that the BJC paper is authored by people at Christie's.

Labels: AZD6244, BRAF, PLX4032

Another snappy blog title...There's a new trial of the promising drug formerly known as PLX4032 or RG7204, now known as RO5185426, as Hoffmann-Roche have a collaboration agreement with the original developer (Plexxikon)

There is a phase 2 trial just started, details here. It is encouraging that this is a phase 2 trial, but they haven't published the results of the previous Phase 2 trial yet.

It's looking reasonably hopeful, as I reported back in June., and there are a couple of people on the melanoma board hoping to go on the trial.

New results for the Phase 1 extension trial are more hopeful still than the initial phase 1 trial I reported on earlier. 70% response rate (compared with about 15% for the standard treatment), one complete response (cure), and an approximate average of 30% tumour shrinkage. Other treatments have looked good at this stage, so let's not get over-excited, but looking good so far.

When viewing the response rate, it should be borne in mind that if your tumours do not have a mutation (BRAF^V600E ) which is present in 50% of melanomas, you won't get the drug, so it is only perhaps twice as good as the standard treatment in terms of response rates. The manufacturer are developing a test kit for the mutation alongside the drug to screen for people it might help.

Labels: PLX4032, RG7204, RO5185426