%), and received no prior chemotherapy for advanced or metastatic disease (66%). The distribution of BRAF V600 mutations was BRAF V600E (87%), V600K (12%), or both (<1%). The median durations of follow-up prior to initiation of alternative treatment were 4.9 months for patients treated with MEKINIST and 3.1 months for patients treated with chemotherapy. Fifty-one (47%) patients crossed over from the chemotherapy arm at the time of disease progression to receive MEKINIST.
Trial 1 demonstrated a statistically significant increase in progression-free survival in the patients treated with MEKINIST. Table 4 and Figure 1 summarize the PFS results.
Table 4. Investigator-Assessed Progression-Free Survival and Confirmed Objective Response Results MEKINIST
N = 214
Chemotherapy
N = 108
PFS
Number of Events (%) 117 (55%)
77 (71%)
Progressive Disease 107 (50%)
70 (65%)
Death 10 (5%)
7 (6%)
Median, months (95% CI) 4.8 (4.3, 4.9)
1.5 (1.4, 2.7)
HRa (95% CI)
P value (log-rank test) 0.47 (0.34, 0.65)
P<0.0001
Confirmed Tumor Responses
Objective Response Rate 22%
8%
(95% CI) (17, 28)
(4, 15)
CR, n (%) 4 (2%)
0
PR, n (%) 43 (20%)
9 (8%)
Duration of Response
Median, months (95% CI) 5.5 (4.1, 5.9)
NR (3.5, NR)
a Pike estimator.
CI = confidence interval; CR = complete response; HR = Hazard Ratio; NR = Not reached, PFS = Progression-free Survival; PR = partial response.
Figure 1. Kaplan-Meier Curves of Investigator-Assessed Progression-Free Survival (ITT population)
In supportive analyses based on independent radiologic review committee assessment, the PFS results were consistent with those of the primary efficacy analysis.
14.2 Lack of Clinical Activity in Metastatic Melanoma Following BRAF Inhibitor Therapy
The clinical activity of MEKINIST was eva luated in a single-arm, multicenter, international trial (Trial 2) in 40 patients with BRAF V600E or V600K mutation-positive, unresectable or metastatic melanoma who had received prior treatment with a BRAF inhibitor. All patients received MEKINIST at a dose of 2 mg orally once daily until disease progression or unacceptable toxicity.
The median age was 58 years, 63% were male, all were white, 98% had baseline ECOG PS of 0 or 1, and the distribution of BRAF V600 mutations was V600E (83%), V600K (10%), and the remaining patients had multiple V600 mutations (5%), or unknown mutational status (2%). No patient in Trial 2 achieved a confirmed partial or complete response as determined by the clinical investigators.
16 HOW SUPPLIED/STORAGE AND HANDLING
0.5 mg Tablets: Yellow, modified oval, biconvex, film-coated tablets with ‘GS’ debossed on one face and ‘TFC’ on the opposing face and are available in bottles of 30 (NDC 0173-0849-13).
1 mg Tablets: White, round, biconvex, film-coated tablets with ‘GS’ debossed on one face and ‘LHE’ on the opposing face and are available in bottles of 30 (NDC 0173-0858-13).
2 mg
