Promising combination treatment for most aggressive form of skin cancer

New data have been presented at the European Association of Dermato Oncology (EADO) Congress on the investigational MEK inhibitor cobimetinib (GDC-0973) in combination with BRAF^V600 inhibitor Zelboraf^® (vemurafenib) for metastatic melanoma.

The findings illustrate that cobimetinib and vemurafenib can be safely co-administered and that the combination shows promising anti-tumour activity, with a median progression-free survival (mPFS) of 13.7 months for BRAF inhibitor-naive patients.(1)

New data have been presented at the European Association of Dermato Oncology (EADO) Congress on the investigational MEK inhibitor cobimetinib (GDC-0973) in combination with BRAF^V600 inhibitor Zelboraf^® (vemurafenib) for metastatic melanoma.

The findings illustrate that cobimetinib and vemurafenib can be safely co-administered and that the combination shows promising anti-tumour activity, with a median progression-free survival (mPFS) of 13.7 months for BRAF inhibitor-naive patients.(1)

An 87% tumour response rate was achieved across BRAF inhibitor-naive patients, with the majority of responses observed within the first 6 weeks of treatment initiation and an additional 10% achieved disease stabilisation.(1) Ten per cent of the group had no radiological evidence of their cancer after treatment.(1) Eighty-three per cent of participants were still alive 1 year after they first began receiving cobimetinib and vemurafenib combined.(1)

“The data are encouraging and represent a notable development in the treatment of metastatic melanoma,” Dr James Larkin, Consultant Medical Oncologist at The Royal Marsden, said. “In the combination of the MEK inhibitor cobimetinib and the BRAF inhibitor vemurafenib, to see an average progression free survival in excess of 12 months provides a welcome indication of the progress in this therapy area. Advanced melanoma is an aggressive cancer affecting many people, and we look forward to the primary results of coBRIM, through which we can further establish the benefits this combination may offer them.”

Dr Larkin is Principal Investigator for coBRIM (GO28141), the ongoing phase III study conducted by Roche to evaluate the efficacy and tolerability of the cobimetinib and vemurafenib combination, compared with vemurafenib alone, in patients with previously untreated BRAF^V600mutation-positive, unresectable locally advanced or metastatic melanoma, the most aggressive form of skin cancer.(2) The primary results of coBRIM are expected later this year.

The findings presented at EADO are the results of BRIM7, an open-label, dose-finding and dose-expansion phase Ib study evaluating the safety and tolerability of this novel combination. In addition to the aforementioned, the BRIM7 research demonstrated evidence of activity for patients whose condition had previously progressed on vemurafenib alone.(1) For these people, the response and stable disease rates were 15% and 42%, respectively.(1) The mPFS observed in this group was 2.8 months, and 32% were alive 1 year after their treatment began.(1)

Across all treated patients, the most common adverse events included diarrhoea (64%), non-acneiform rash (60%), fatigue (48%), nausea (45%), liver laboratory test abnormality (40%) and photosensitivity/sunburn (40%). The most frequently reported Grade 3 events were liver laboratory test abnormality (11%), cutaneous squamous cell carcinoma (9%), non-acneiform rash (8%), anaemia (7%), joint pain (6%), fatigue (5%) and diarrhoea (5%).(1)

There has been a significant rise in melanoma cases in recent years.(3) Today, more than 13,000 people develop the condition annually in the UK compared with 1,800 in 1975.(4) Advances in treatment have meant that more than eight in ten people with melanoma survive for 5 years or longer following their diagnosis.(3) However, the latest statistics tell us that approximately 2,000 malignant melanoma patients die every year,(4) making continued research and development in this therapy area essential.

References

1.        Ribas A, et al. BRIM7-Vemurafenib + cobimetinib Phase 1B study in BRAF mutant melanoma. Oral presentation to be presented at 10th European Association of Dermato-Oncology (EADO); Vilnius, Lithuania, 7–10 May 2014.
2. National Institutes of Health. A phase 3 study comparing GDC-0973, a MEK inhibitor, in combination with vemurafenib vs. vemurafenib alone in patients with metastatic melanoma. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01689519 (accessed May 2014).
3. Cancer Research UK. Skin Cancer Statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/skin/ (accessed May 2014).
4. Cancer Research UK. Press release: Skin cancer rates five times higher than in 70s. Available at: http://www.cancerresearchuk.org/about-us/cancer-news/press-release/skin-cancer-rates-five-times-higher-than-in-70s (accessed May 2014).