My Malignant Melanoma

Seanty's experiences with Metastatic Malignant Melanoma. Part of Email us direct at

Friday, 21 June 2013


Ben's Story

There's a new melanoma story in the In Memoriam section: Ben's story

Tuesday, 18 June 2013


Hottest Prospects

I'm told that the hottest new prospects for MM treatment at last week's ASCO conference were thought to be:

1. Combination therapy of BRAF and MEK inhibitors from GSK (Tafinlar/dabrafenib plus Mekinist /trametinib) - headline: resistance only develops after 9 instead of 6 months

2. Merck anti-PD1(Lambrolizumab) - headline: good initial response rate, relatively mild side-effects

3. BMS anti-PD1 (MDX-1106) plus Ipilimumab / Yervoy - headline: good results although 50% had nasty side effects

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Wednesday, 12 June 2013


Treatments Update

There are so many new drugs coming through that it's hard to keep up. Here's a summary of drugs and their targets (mostly simplified from Wikipedia entries). Let me know if I've missed any, I know there are lots more under these target headings which just have codes for names at present.


BRAF is a human gene that makes a protein called B-Raf. The B-Raf protein is involved in sending signals inside cells, which are involved in directing cell growth. In 2002, it was shown to be faulty (mutated) in human cancers. Drugs that treat cancers driven by BRAF have been developed. Two of these drugs, vemurafenib and dabrafenib are approved by the US FDA for treatment of late-stage melanoma.

Dabrafenib /Tafinlar

Dabrafenib acts as an inhibitor of B-Raf. Dabrafenib has clinical activity with a manageable safety profile in clinical trials of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma. It was approved for use against melanoma by the FDA in May 30th, 2013.

Vemurafenib / Zelboraf

is a B-Raf enzyme inhibitor developed for the treatment of late-stage melanoma. Vemurafenib received FDA approval for the treatment of late-stage melanoma on August 17, 2011, Health Canada approval on February 15, 2012 and on February 20, 2012, the European Commission approved vemurafenib as a monotherapy for the treatment of adult patients with BRAF V600 mutation positive unresectable or metastatic melanoma, the most aggressive form of skin cancer.


A drug by Novartis disclosed at the spring 2013 American Chemical Society meeting in New Orleans to treat melanoma with a V600E mutation in the B-RAF kinase which it inhibits. The drug is currently undergoing Phase II trials.


A MEK inhibitor is a chemical or drug that inhibits a biochemical switch upstream of the gene which produces B-Raf, which is often overactive in BRAF-mutated melanoma. Hence MEK inhibitors can both work as standalone drugs, and increase the effectiveness of BRAF drugs.

Trametinib /Mekinist

is a MEK inhibitor drug with anti-cancer activity. It inhibits MEK1 and MEK2. In May 2013, trametinib was approved by the FDA for the treatment of melanoma.


Cytotoxic T lymphocytes (CTLs) can recognize and destroy cancer cells. However, there is also an inhibitory mechanism via a gene called CTLA-4 that interrupts this destruction. CTLA-4 inhibitors turn off this mechanism and allows CTLs to continue to destroy cancer cells.

Ipilimumab /Yervoy

Ipilimumab was approved by the FDA in March 2011 to treat patients with late-stage melanoma that has spread or cannot be removed by surgery. On February 1, 2012, Health Canada approved ipilimumab for "treatment of unresectable or metastatic melanoma in patients who have failed or do not tolerate other systemic therapy for advanced disease." Additionally Ipilimumab was approved in both the UK and European Union (EU), for second line treatment of metastatic melanoma, November 2012.

Zanolimumab/ HuMax-CD4

Action as ipilimumab. The drug is currently undergoing Phase II trials.


Researchers have shown that several tumour types are able to hide in plain sight by establishing a "molecular camouflage" that deceives the body's immune system into thinking they are normal and therefore allow them to grow unchecked. By utilizing the PD-1 pathway, a tumour cell can prevent the activation of T-cells and therefore may block a key step that triggers the immune system. Drugs targeting this pathway can remove the cells "camouflage", allowing the body to destroy them.

Lambrolizumab / MK-3475

is an antibody drug in development by Merck that targets the PD-1 receptor. The drug is intended for use in treating metastatic melanoma. Lambrolizumab is being studied in multiple cancer types including melanoma.


Nivolumab is  an antibody drug which acts on the PD1 receptor. A Phase 1 clinical trial tested nivolumab at doses ranging from 0.1 to 10.0 mg per kilogram of body weight, every 2 weeks. Response was assessed after each 8-week treatment cycle, and were evaluable for 236 of 296 patients. Study authors concluded that:"Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non–small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use." Phase III clinical trials of nivolumab are recruiting in the US and EU.


is an immune booster. In 1999, FDA granted Allovectin-7 orphan drug designation for the treatment of invasive and metastatic melanoma.

Talimogene laherparepvec/ T-VEC

Talimogene laherparepvec, often simply called "T-VEC" is a cancer-killing (oncolytic) virus currently being studied for the treatment of melanoma and other advanced cancers. The drug was initially developed by BioVex, Inc. under the name OncoVEX GM-CSF until it was acquired by Amgen in 2011. With the announcement of positive results in March 2013, T-VEC is the first oncolytic virus to be proven effective in a Phase III clinical trial

I have updated my pages on experimental and established drugs to reflect the new possibilities. It hasn't been necessary to update my alternative medicine page - it still doesn't work.

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Tuesday, 11 June 2013


Update : PD-1 drugs

I'm told that UK trials of the new and highly promising PD1 antibodies for treatment-naive patients with advanced melanoma start in the next few weeks at Royal Marsden, Manchester and Southampton.

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Sunday, 9 June 2013


New class of melanoma drugs may be curative

Saw in the New Scientist today that there are a number of really promising new drugs for MM coming through: Lambrolizumab and Nivolumab, which both work on the PD-1 receptor, and a so far unnamed drug which works on another receptor.

All give great reductions in tumour volume, and there all in all cases apparent complete cures. They all work by rebooting the immune system, in just the same way as quack diets claim to do, but actually don't.

In other news, it seems that mucosal melanoma is really a different disease from cutaneous melanoma.

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