Skip to main content

New skin cancer drug performs well

Thursday 23 February 2012

A study of a new drug for advanced skin cancer has shown it “almost doubles survival times”, BBC News has reported.

The drug, called vemurafenib, was tested in a clinical trial that examined its impact on tumour size and survival in patients with advanced melanoma skin cancer that had spread to other parts of the body. The outlook for this type of cancer is generally poor as it's an aggressive cancer with few treatment options and patients tend to survive for less than a year. Researchers found that approximately half of the patients responded to the drug and that the overall survival rate in these patients was nearly 16 months, on average.

This study provides evidence on the effectiveness of a new drug, vemurafenib, for treating some patients with metastatic melanoma. Because the drug works by targeting a specific genetic mutation, it won’t be suitable for patients who aren’t carrying the mutation, which is found in around half of patients with melanoma that has spread. Additionally, while the drug has been recommended for approval, it hasn't yet been approved for use in Europe; it is unclear at this point if and when it will be available for treatment in the UK, although the National Institute for Health and Clinical Excellence (NICE) is said to be currently assessing it.

Where did the story come from?

The study was carried out by researchers from Vanderbilt University, the Hoffman-La Roche pharmaceutical company and other institutions throughout the US and Australia. The research was supported by Hoffmann-La Roche, who are the manufacturers of vemurafenib.

The study was published in the peer-reviewed New England Journal of Medicine.

The BBC covered this research appropriately, emphasising the positive results but also highlighting that the drug had yet to be approved in the UK and wouldn’t be suitable for all patients with metastatic melanoma. The broadcaster also reported on some of the limitations of the research methods.

What kind of research was this?

This was a phase II clinical trial that examined how effective a drug called vemurafenib was at inducing a clinical response and its impact on overall survival in a set of patients with metastatic melanoma. Malignant melanoma is a relatively rare but aggressive type of skin cancer that can be particularly hard to treat when caught at an advanced stage. All of the patients in the trial carried a specific genetic mutation called the “BRAF V600 mutation”, which leads to the abnormal activation of an enzyme involved in cell growth and death. Previous research indicates that vemurafenib blocks the action of this enzyme.

Phase II trials are designed to assess the effects of new drugs in highly controlled settings. These trials don’t normally employ a group of control patients receiving other forms of treatment, and so generally can’t be used to tell how a new drug compares against standard or existing treatments. These types of control-group comparisons are usually performed in phase III trials. Phase II trials are, however, a key part of the development of new drugs, and are used as a confirmatory step before a drug can be given to wider research populations.

Media coverage of this trial has compared the survival rates of patients receiving vemurafenib with those seen in general patients with metastatic melanoma, rather than patients directly involved in the study. While such comparisons are useful for readers to understand more about the drug, formal scientific comparisons of different treatments have to account for a range of important factors, such as patients’ medical histories or how advanced the cancer is when treatment is started.

What did the research involve?

Researchers enrolled 132 patients with stage IV metastatic melanoma (stage IV cancer means it has spread to other parts of the body, such as the lungs or liver). They all carried a form of BRAF V600 genetic mutation. All patients had previously been treated for the disease, and they all received the same dose of the drug vemurafenib twice a day. The patients stopped taking the drug if they experienced unacceptable side effects or if their disease progressed.

The patients underwent tumour imaging (either magnetic resonance imaging (MRI) or computed tomography (CT)) at the beginning of the study and every six weeks thereafter. Researchers used these scans to assess any changes in tumour size and response to the treatment.

Researchers then analysed the data to determine the proportion of patients who responded to treatment.

What were the basic results?

The patients were followed up for an average (median) of 12.9 months. The researchers found that:

  • Overall, 53% of patients showed some reduction in the size of their tumour measured at the start of the study.
  • Among those that responded, eight patients achieved a complete response (6% of the total study group), and 62 patients (47%) achieved a partial response (47% of the total study group).
  • Of the patients who responded to treatment, 23 (33% of responders) maintained that response at the end of the study.
  • The median duration of response was 6.7 months (95% CI 5.6 to 8.6 months).
  • Median overall survival was 15.9 months (95% CI 11.6 to 18.3 months), and 62 patients (47%) were still alive at the end of the study.
  • The overall survival rate at six months was 77% (95% CI 70% to 85%), at twelve months was 58% (95% CI 49% to 67%,) and at eighteen months was 43% (95% CI 33% to 53%).

Most patients experienced at least one side effect due to the study drug. The most commonly reported side effects were joint pain, rash, fatigue, sensitivity to light and hair loss. Four patients (3%) stopped taking the drug due to side effects. One patient died due to a rapid progression of the melanoma along with kidney failure; the researchers said this may have been related to taking vemurafenib but this was not certain.

How did the researchers interpret the results?

The researchers concluded that vemurafenib effectively targets metastatic melanoma tumours in patients with BRAF V6000 mutations, and that response rates are higher than those seen with other treatments.


This study has shown that patients with a specific mutation and advanced metastatic melanoma have a high response rate to a new drug, vemurafenib. Currently, treatment options for people with metastatic melanoma can involve chemotherapy, radiotherapy or immune therapies, but even with treatment the outlook is usually poor once their cancer has spread. Often, people with late-stage disease may be enrolled in clinical trials such as this to try and find more effective treatments.

Researchers say that the long follow-up of their study provides initial evidence on the overall survival of patients receiving this drug, something that phase III studies have so far not been able to demonstrate.

Researchers point out, however, that patients do develop resistance to vemurafenib, and that further research is needed to determine how this occurs.

Previous studies have shown that patients with metastatic melanoma have an average survival rate of 6 to 10 months, as mentioned in some news coverage. However, it is difficult to compare this estimate to survival times seen in the current study, as the patient populations may be different. For example, it’s unclear whether these studies enrolled patients with the same genetic mutation, or how survival may be different between those with and without the mutation.

This study adds to the mounting evidence of the effectiveness of vemurafenib as a treatment of metastatic melanoma with BRAF V600 mutation. While this phase II study cannot directly demonstrate effectiveness compared to standard care, an additional phase III study has been conducted that randomised patients to receive vemurafenib or standard therapy. This study was stopped before it was complete, as an interim analysis indicated that vemurafenib significantly improved patients' progression-free survival and six-month survival, compared with standard care. At this point, all of the participants were given the new drug.

All in all, this is very promising research for the treatment of an aggressive cancer for which there are few existing options. At present the drug has been recommended for approval by the European Medicines Agency, and is currently being evaluated by NICE for use in the UK.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Skin cancer drug hopes raised by study

BBC News, 23 February 2012

Links to the science

Sosman JA, Kim KB, M.D., Schuchter L et al.

Survival in BRAF V600 Mutant Advanced Melanoma Treated with Vemurafenib

New England Journal of Medicine 2012; 366:707-714