* Similar results with BRAF/MEK combinations in melanoma
* Different side effects may determine choice of regimen
By Ben Hirschler
MADRID, Sept 29 (Reuters) - Rival two-pill combinations formelanoma from Roche and GlaxoSmithKline haveyielded similar results in separate clinical trials, leavingdoctors with little to choose between the two regimens.
Roche's combination is not yet available but GSK is alreadymarketing its combined treatment, though it now plans to sellthe drugs involved and other oncology products to Novartis under a deal announced in April.
Both the combinations are designed to block two proteins,known as BRAF and MEK, that are associated with tumour growthand are implicated in about half of all cases of metastaticmelanoma, where disease has spread to other parts of the body.
In the 495-patient study sponsored by Roche, patients giventhe company's Zelboraf drug and an experimental compound calledcobimetinib lived a median 9.9 months before their diseaseworsened, against 6.2 months when they took Zelboraf alone.
GSK's trial, involving 704 patients, showed its combinationof the drugs Tafinlar and Mekinist increased progression-freesurvival by 11.4 months versus 7.3 months seen for patients onZelboraf.
In both cases, patients were selected for inclusion in the studies after they had been shown to have a genetic mutationmaking them sensitive to such treatments.
The findings from the two studies were presented on Mondayat the European Society of Medical Oncology annual congress inMadrid. The Roche study was also published online in the NewEngland Journal of Medicine (NEJM).
Reinhard Dummer of the University of Zurich Hospital, whowas not involved in the tests, said the results were verysimilar and the clear improvement seen in both cases provided"convincing evidence" that such combination therapy should beused routinely.
"There is hardly any space for monotherapy now," he said.
SIDE EFFECTS
Given the almost identical clinical outcomes, choosingbetween the two regimens will likely come down to the slightlydifferent side effect profiles of the two BRAF inhibitors usedin the combinations, Dummer added.
GSK's Tafinlar is linked to a higher rate of fever, whileRoche's Zelboraf is linked to photosensitivity, which can causesevere sunburn, and Dummer said this could make it less suitablefor patients living in sunny climates.
Roche plans to submit its combination to regulators aroundthe world for approval. Cobimetinib, the second experimentalpill 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 associatedwith disease. This approach can have dramatic effects in theshort term but tumour cells tend to go on to develop resistance.
While combining two drugs extends the response, oncologistsare also looking at ways to generate a much more durable effect,with attention now focusing on immunotherapy treatments that canoffer longer-term benefits.
"Evidence suggests that these agents can lead to durabletumour responses in patients with metastatic melanoma, albeitwith lower response rates than have been observed with BRAF andMEK inhibition," researchers on the Roche study wrote in theNEJM.
More than 230,000 people worldwide are diagnosed withmelanoma each year, according to the World Health Organisation.If the disease is caught early, it can be cured - but mostpeople with advanced melanoma have a poor prognosis. (Reporting by Ben Hirschler; Editing by Michael Urquhart)