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Posts tagged ‘vemurafenib’

Update on RAF resistance in metastatic melanoma

“RAF inhibitors (vemurafenib and dabrafenib) have profound clinical activity in patients with BRAF-mutant melanoma, but their therapeutic effects are limited by the emergence of drug resistance.”

Solit and Rosen (2014)

For today’s post on Science Fridays, I wanted to take a look at an overview paper, published in Cancer Discovery, from two researchers in the metastatic melanoma field who have been looking at multiple mechanisms of resistance.  It’s an important topic because while we have seen incremental improvements in outcomes for this disease, the 5-year survival rate is still rather poor with only 10–20% of metastatic patients still alive by then.  This is not to disparage the efforts of scientists, clinicians or companies working in this space, far from it, but there is is clearly a need for new therapies, strategies and combinations, given the high unmet medical need that exists.

Overcoming resistance to vemurafenib in metastatic melanoma

One of the interesting themes for that emerged for me at AACR this year was the amount of effort that is being expended on strategies to overcome drug resistance. This was particularly noticeable in metastatic melanoma and non-small cell lung cancer (NSCLC).  More on lung cancer in another post, as today I want to focus on melanoma.

In the advanced melanoma, vemurafenib is given to patients with the BRAFV600E mutation, which occurs in approximately 50% of patients. This oncogene drives activity of the tumour, but inhibition with vemurafenib (Zelboraf) has shown some remarkable effects, as the stunning before and after photos from Levi Garraway’s group demonstrate.

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ASCO 2012 Update 2: Overcoming resistance in metastatic melanoma

ASCO 2012 Posters 300x225 ASCO 2012 Update 2: Overcoming resistance in metastatic melanomaFollowing on from my preview of the 2012 American Society of Clinical Oncology (ASCO) meeting, I am now working through updates on some of the hot topics.

I’m delighted to announce The Chemical & Engineering News blog ‘The Haystack’, have published my second guest post on advances in metastatic melanoma.

This is a devastating disease that has seen very few advances over the last decade since the approval of dacarbazine (DTIC) until last year when the FDA approved two new therapies in vemurafenib (Zelboraf) for patients with the BRAFV600E mutation and ipilumumab (Yervoy), an immunotherapy that targets CTLA4.

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A new opportunity for vemurafenib in BRAFV600E colon cancer

There’s been quite a flurry of commercial news on the Pharma front this morning, with Amgen buying Micromet (whose leading product is blinatumumab in ALL) and Celgene announcing their acquisition of Avila Therapeutics who have a Bruton Kinase Inhibitor (BTK) AVL-292 in phase IB development for lymphomas, which was all the rage at the recent American Society of Hematology (ASH) meeting last month.

The big news for me today, though, wasn’t the commercial acquisitions but a gem of a paper relating to science and its significance for future cancer treatment.

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When is NICE is not so nice?

“Ipilimumab is not recommended for the treatment of advanced (unresectable or metastatic) malignant melanoma in people who have received prior therapy.

The Committee was satisfied that ipilimumab meets the criteria for being a life-extending, end-of-life treatment and that the trial evidence presented for this consideration was robust.

The Committee acknowledged that few advances had been made in the treatment of advanced melanoma in recent years and ipilimumab could be considered a significant innovation for a disease with a high unmet clinical need.

Zelboraf approved by the FDA in BRAF V600E metastatic melanoma

This morning the FDA approved vemurafenib (Zelboraf), along with it’s companion diagnostic, for the treatment of metastatic melanoma in patients with the BRAF V600E mutation.

This is great news!

ZELBORAF logo 300x116 Zelboraf approved by the FDA in BRAF V600E metastatic melanoma

The approval has been granted ahead of time, as correctly mentioned in the Reuters article recently. This means we now have two new therapies for the treatment of metastatic melanoma after ipilimumab (Yervoy) was approved in March.

These two new drugs have been rapidly approved within the space of a couple of months following the presentation of the data at the ASCO plenary session in June.

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Will vemurafenib receive early approval for metastatic melanoma?

A Reuters press release on vemurafenib (Zelboraf) caught my eye this morning, suggesting that it might be approved in BRAFV600E metastatic melanoma by the FDA might be “imminent” according to an unnamed source and much earlier than the expected PDUFA date in November October 28th (now confirmed by Roche/Genentech).

If so, that’s very good news.

However, what really caught my eye was a quote from a spokesperson at Roche Diagnostics, suggesting that the BRAFV600E test would could around $150.  That’s lower than I was expecting, although no doubt it will be considerably offset by the cost of vemurafenib itself.

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BRAF mutations in hairy cell leukemia

Last month an interesting article was published in The New England Journal of Medicine describing how BRAFV600E mutations may have a key role to play in hairy cell leukemia (HCL), which came out around the same time as the European Hematology Association (EHA) meeting that I attended in London.  The news certainly caused a buzz at the conference!

Hairy cell leukemia BRAF mutations in hairy cell leukemia

Source: Wikipedia

Hair cell leukemia is a fairly rare type of leukemia that affects B cells (lymphocytes), which are distinguished by their hairy like appearance under the microscope because they have fine projections coming from their surface.

European Hematology Association meeting 2011

Well, after just getting back from the American Society of Clinical Oncology (ASCO) meeting in Chicago, I’m heading off to Europe for the European Hematology Association (EHA) meeting – no rest for the wicked!

ASCO was a rather flat meeting this year – the stars were undoubtedly the imatinib 36 vs 12 month data in adjuvant GIST (clearly superior) and Roche/Plexxikon/Daiichi Sankyo’s vemurafenib in BRAF V600E metastatic melanoma. The ipilimumab data was strangely disappointing in the upfront setting – only 2 months improvement in survival when added to DTIC.

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BMS and Roche join forces in metastatic melanoma

Two of the most dynamic cancer markets at the moment are prostate cancer and metastatic melanoma, which is great news considering that neither has had much attention over the last decade compared to breast and lung cancers.

My colleague has posted an overview of what’s going on in advanced prostate cancer today, which you may be interested in checking out pre-ASCO.  However, what excited me this morning were announcements from BMS and Roche declaring their intent to pursue combination trials in BRAF metastatic melanoma with their therapies ipilimumab (Yervoy) and vemurafenib (PLX4032).

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