UPDATE 1-Roche, GSK melanoma pill combinations look similar in showdown

Source: Reuters.com, September 2014

Roche set to compete with established GSK combination

  • Similar results with BRAF/MEK cocktails in melanoma
  • Different side effects may determine choice of regimen
  • Shares in Roche’s biotech partner Exelixis jump 20 pct (Adds Exelixis share price jump, more on treatment debate)

MADRID, Sept 29 (Reuters) – Rival two-pill combinations for melanoma from Roche and GlaxoSmithKline had similarly good results in separate clinical trials, leaving doctors with little to choose between the two skin cancer courses.

The latest findings will fuel a wider debate about the optimal treatment of melanoma as a new generation of immune-stimulating injections offers an alternative way to fight the deadliest form of skin cancer.

Roche’s combination — which includes a drug discovered by Exelixis, whose shares jumped some 20 percent in premarket trade on the study news — is not yet available. GSK is already marketing its combined treatment.

GSK, however, plans to sell its melanoma drugs and other oncology products to Novartis under a deal announced in April.

Both combinations are designed to block two proteins, known as BRAF and MEK, that are associated with tumour growth and are implicated in about half of all cases of metastatic melanoma, where the disease has spread to other parts of the body.

In the 495-patient study sponsored by Roche, patients given the company’s Zelboraf drug and the experimental compound cobimetinib lived a median 9.9 months before their disease worsened, against 6.2 months when they took Zelboraf alone.

GSK’s trial, involving 704 patients, showed its combination of the drugs Tafinlar and Mekinist increased progression-free survival by 11.4 months versus 7.3 months for patients on Zelboraf.

In both cases, patients were selected for inclusion in the studies after they had been shown to have a genetic mutation making them sensitive to such treatments.

The findings from the two studies were presented on Monday at the European Society of Medical Oncology annual congress in Madrid. The Roche study was also published online in the New England Journal of Medicine (NEJM).

Reinhard Dummer of the University of Zurich Hospital, who was not involved in the tests, said the results were very similar and the clear improvement seen in both cases provided “convincing evidence” that such combination therapy should be used routinely.

“There is hardly any space for monotherapy now,” he said.


Given the almost identical clinical outcomes, choosing between the two regimens will likely come down to the slightly different side effect profiles of the two BRAF inhibitors used in the combinations, Dummer said.

GSK’s Tafinlar is linked to a higher rate of fever, while Roche’s Zelboraf is linked to photosensitivity, which can cause severe sunburn. Dummer said this could make it less suitable for patients living in sunny climates.

Roche plans to submit its combination to regulators around the world for approval.

Cobimetinib, the second experimental pill in the Roche combination, is being developed with U.S. biotech company Exelixis.

All these pills are examples of targeted cancer drugs, designed to turn off very specific molecular pathways associated with disease. This approach can have dramatic effects in the short term but tumour cells tend to go on to develop resistance.

While combining two drugs extends the response, oncologists are also looking at ways to generate a much more durable effect, with attention now focusing on immunotherapy treatments that can offer longer-term benefits.

“Evidence suggests that these agents can lead to durable tumour responses in patients with metastatic melanoma, albeit with lower response rates than have been observed with BRAF and MEK inhibition,” researchers on the Roche study wrote in the NEJM.

Working out when to use the BRAF/MEK inhibitors and when to use immunotherapy is the next question oncologists aim to tackle with a new programme of clinical testing.

More than 230,000 people worldwide are diagnosed with melanoma each year, according to the World Health Organisation. If the disease is caught early, it can be cured — but most people with advanced melanoma have a poor prognosis

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