Safety of ipilimumab in patients (pts) with untreated, advanced melanoma alive beyond 2 years: Results from a phase III study (#729)
Background: In a phase 3 study (CA184-024) of previously untreated pts with stage III or IV melanoma, IPI + dacarbazine (DTIC) significantly improved overall survival (OS) vs. DTIC alone (Robert et al. NEJM 2011). We now report safety data of IPI in pts from this study alive >2 yrs from study initiation.
Methods: Pts with untreated advanced melanoma, were randomized to IPI (10 mg/kg) + DTIC (850 mg/m2) or placebo + DTIC (850 mg/m2) given at Wks 1, 4, 7, 10 followed by DTIC q 3 wks through Wk 22. Eligible pts (stable disease or better) received IPI or placebo q 12 wks as maintenance. Immune-related adverse events (irAEs) occurring after 2 yrs were evaluated as was safety in subjects receiving IPI dosing after 2 yrs.
Results: In the IPI + DTIC group 68 (28%) pts survived >2 yrs compared with 44 (18%) in the DTIC alone group. In the IPI+ DTIC group, 7.4% of pts (5/68) experienced irAEs including grade 3/4 rash/pruritus (n=1), low-grade rash (n=3), pruritus (n=2), skin hypopigmentation, and elevated ALT / AST (n=1). Of 11 pts receiving IPI dosing for ≥2 yrs, 3 experienced irAEs: grade 3/4 rash/pruritus (n=1); low-grade events included rash/pruritus (n=2) and elevated ALT/AST (n=1). No gastrointestinal or endocrine events (any grade) were observed.
Conclusions: In Study 024, IPI + DTIC treatment improved OS in pts with untreated, advanced melanoma with higher survival rates in the IPI + DTIC group at 1 yr, 2 yrs and 3 yrs (HR 0.72, p<0.001). The IPI safety profile beyond 2 yrs survival suggests that treatment with IPI + DTIC is associated with low rates of irAEs in these pts. For patients receiving active IPI treatment ≥2 yrs, the safety profile appears to be consistent with the known safety profile of IPI.