Bringing the Oncology Community Together

BRIM-2 Upholds Benefits Emerging with Vemurafenib in Melanoma

Oncology & Biotech News
Published Online: Monday, July 25, 2011
Antoni Ribas, MD

Antoni Ribas, MD

In patients with metastatic melanoma, the BRAF inhibitor vemurafenib led to high objective response rates (ORRs) and durable treatment responses in an open-label phase II study presented at ASCO 2011 by Antoni Ribas, MD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.

“A significant number of patients have ongoing responses between 10 and 12 months from the study start,” said Ribas. “Overall survival (OS) is 58% at 12 months. Median OS has not been reached.”

The study was initiated after the highly encouraging phase I results of the drug in 32 patients with a V600E activating mutation in the BRAF gene. In that study, vemurafenib led to a high incidence of tumor regression and an unconfirmed ORR of 81%. This high ORR has since been downgraded to a confirmed ORR of 53%.

The phase II BRIM-2 trial, which enrolled 132 previously treated patients, essentially validated the initial findings of high activity for the novel agent.

Table. Patient Baseline Disease Characteristics

No. (%)
N = 132
Stage at diagnosis

33 (25)
18 (14)
81 (61)
Serum LDH

67 (51)
65 (49)
No. prior therapies

67 (51)
36 (27)
29 (22)
Previous ipilimumab or

125 (95)
7 (5)

LDH indicates lactate dehydrogenase.
Adapted from Ribas et al. J Clin Oncol. 2011;29(suppl; abstr 8509).

Patients who had received at least 1 prior line of therapy for metastatic melanoma (49% had received 2 or more) received vemurafenib 960 mg PO BID until progression, unacceptable toxicity, or death. The primary endpoint was ORR by independent review.

At a median follow-up time of 10 months, the ORR was 53%, which met the study’s primary endpoint (a target ORR of 30% and lower boundary of 95% confidence interval of at least 20%). Stable disease was noted in 29% of patients, Ribas reported.

In the prespecified exploratory subset analysis, there were no differences in response rates according to age, gender, performance status, stage, number of prior therapies, or receipt of high-dose interleukin-2. Patients with high baseline lactate dehydrogenase (LDH) (>1.5 times upper limit of normal), however, were less likely to respond than those with normal LDH, he reported.

Median progression-free survival (PFS) was 6.7 months. OS was 77% at 6 months and 58% at 1 year. Median duration of response was 6.7 months, but responses are ongoing for as long as a year in many patients. Ribas added that time to response can also be delayed in some patients, even up to 1 year from start of therapy. At this time, 27% of patients are still on study.

The drug was well tolerated, with the most common side effects being arthralgias (58%), skin rash (52%), and photosensitivity (52%). He said that squamous cell carcinomas develop in about 25% of patients, tend to appear within the first 2 months, and are easily managed.

Dose modifications were necessary in 45% of patients; however, the median daily dose— 1750 mg—was 91% of the intended total dose. Only 4 patients discontinued due to drugrelated adverse events.

Page: 12Next Page (2) >>
Related Articles
PD-L1 Predictive of Response to MK-3475 in Melanoma and NSCLC
PD-L1 levels adequately predict response and clinical outcomes for PD-1 inhibitor MK-3475 in patients with non-small cell lung cancer (NSCLC) and melanoma
T-VEC Promotes Tumor Shrinkage in Unresectable Melanoma
The oncolytic immunotherapeutic vaccine talimogene laherparepvec (T-VEC) promoted tumor shrinkage in 64% of patients with advanced melanoma, including a marked reduction in the size of uninjected metastatic lesions
Nivolumab Delivers Durable Remissions With Low Toxicity in Advanced Melanoma
Nivolumab, a PD-1-specific antibody, has been shown to produce long-term remissions with limited toxicity in patients with advanced melanoma, according to results from one of the longest follow ups to examine the drug.
New Paradigms Emerge for Translating Immunotherapy Into Broad Clinical Use
Although breakthrough successes are generating a renaissance for anticancer immunotherapies, the framework for translating promising research results into clinical practice remains very much under construction.
Most Popular Right Now
More Reading
External Resources

American Journal of Managed Care
Pharmacy Times
Physicians' Education Resource
Physician's Money Digest
Specialty Pharmacy Times
OncLive Resources

OncLive TV
Oncology Nurses
Web Exclusives

About Us
Advisory Board
Contact Us
Forgot Password
Privacy Policy
Terms & Conditions
Intellisphere, LLC
666 Plainsboro Road
Building 300
Plainsboro, NJ 08536
P: 609-716-7777
F: 609-716-4747

Copyright OncLive 2006-2014
Intellisphere, LLC. All Rights Reserved.