Roche announces phase III study results of Zelboraf for adjuvant treatment of BRAF V600 mutation-positive melanoma

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced data for the phase III BRIM8 study, which was designed to investigate the efficacy and safety of Zelboraf® (vemurafenib) in the adjuvant (after surgery) treatment of people with completely resected, BRAF V600 mutation-positive melanoma. The study assessed two cohorts; stage IIC-IIIB (cohort 1) and stage IIIC (cohort 2) melanoma patients. The study did not meet its primary endpoint of significantly reducing the risk of recurrence (disease-free survival; DFS) in patients with stage IIIC melanoma (cohort 2); however, a 46% reduction in recurrence risk was observed in stage IIC-IIIB patients (cohort 1). The safety profile was consistent with that seen in previous studies of Zelboraf in advanced melanoma.

• People in cohort 2 had a median DFS of 23.1 months with Zelboraf vs. 15.4 months with placebo (HR=0.80; 95% CI 0.54-1.18, p=0.2598).
• For people in cohort 1, median DFS was not reached with Zelboraf compared with median DFS of 36.9 months with placebo, (HR=0.54; 95% CI 0.37-0.79). Due to the pre-specified statistical design of the study, the results for cohort 1 cannot be formally tested for significance.

“While results in people with stage IIIC melanoma were not what we had hoped, the reduction in the risk of recurrence in people with stage IIC-IIIB disease is encouraging and suggests Zelboraf may play a role in this earlier setting,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development.

Full data will be presented today at the European Society of Medical Oncology (ESMO) annual meeting in Madrid, Spain as part of Presidential Symposium III (Abstract #LBA7) from 4.30pm to 5.45pm CET.

The results will also be featured in ESMO’s official press program.

About BRIM8

BRIM8 is a multicentre, randomized, double-blind, two-cohort, placebo-controlled study that investigated the efficacy and safety profile of Zelboraf for the adjuvant treatment of people with completely resected, BRAF V600 mutation-positive melanoma at high risk for recurrence. The primary endpoint was disease-free survival. The study had a Special Protocol Assessment and was designed with two cohorts with a hierarchical analysis where cohort 2 was required to meet the primary endpoint before cohort 1 analysis. People in cohort 1 had completely resected Stage IIC, IIIA or IIIB melanoma; people in cohort 2 had completely resected Stage IIIC melanoma. In the study, 498 people were randomised to receive either oral Zelboraf 960mg or placebo twice daily for 52 weeks.

About melanoma

Melanoma is less common, but more aggressive and deadlier than other forms of skin cancer.^1,2 BRAF is mutated in approximately half of melanomas.³ More than 232,000 people worldwide are currently diagnosed with melanoma each year.⁴ In recent years, there have been significant advances in treatment for metastatic melanoma and people with the disease have more options. However, it continues to be a serious health issue with a high unmet need and a steadily increasing incidence over the past 30 years.⁵ 

About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. Thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry nine years in a row by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2016 employed more than 94,000 people worldwide. In 2016, Roche invested CHF 9.9 billion in R&D and posted sales of CHF 50.6 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

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References

1. Algazi AP, Soon CW, Daud AI. Treatment of cutaneous melanoma: current approaches and future prospects. Cancer Manag Res. 2010;2:197-211.
2. Finn L, Markovic SN, Joseph RW. Therapy for metastatic melanoma: the past, present, and future. BMC Med. 2012;10:23.
3. Ascierto PA, Kirkwood JM, Grob JJ, et al. The role of BRAF V600 mutation in melanoma. J Transl Med. 2012;10:85.
4. International Agency for Research on Cancer. GLOBOCAN 2012, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet; cited 2017 Sept 4]. Available from: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx .
5. Bataille V. Risk factors for melanoma development. Expert Rev Dermatol. 2009;4:533-9.