Results from recent clinical trials presented at the European Society of Medical Oncology annual congress in Madrid, showed that two of the new pill combinations for melanoma treatment from Roche (Zelboraf plus Cobimetinib) and GlaxoSmithKline (Tafinlar plus Mekinist) had similar promising results.
Due to the identical results, the decision of which regimen will prevail will probably depend on the minor differences in side effect profiles of the two BRAF inhibitors used in the combined therapies.
These two combinations are specific BRAF and MEK inhibitors, two proteins involved in the majority of metastatic melanomas.
In Roche’s clinical trial, a total of 495 patients were given either the combination of Zelboraf plus cobimetinib, or Zelboraf alone. Subjects who were administered the combination, lived a median of 9.9 months before their disease progressed, vs 6.2 months for patients who took Zelboraf alone.
GSK’s trial enrolled 704 patients and showed that its combination of Tafinlar and Mekinist increased progression-free survival by 11.4 months versus 7.3 months for patients on Zelboraf.
In terms of side effects, GSK’s Tafinlar showed a higher rate of fever, while Roche’s Zelboraf was associated with photosensitivity, making it less suitable for patients living in sunny climates.
Importantly, in both clinical trials, patients were included only if they carried a genetic mutation which rendered them sensitive to the experimental treatments.
Roche’s combination is not yet available, however the company plans to submit its combination to worldwide regulators for approval. On the other hand, GSK is already marketing its combined treatment.
Both of these pills are designed to turn off specific molecular pathways in tumor cells, resulting in dramatic effects in the short term, but allowing cancers cells to develop resistance.
Even though combining these two drugs can enhance a quick response, researchers are developing new strategies that will allow the generation of drugs with a much durable effect, particularly immunotherapies.
“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,” Roche researchers wrote in their study, published in the New England Journal of Medicine.
