CRA8000 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text].
METHODS: Study CA184008 was an open-label, single-arm study of ipilimumab 10 mg/kg. Study CA184022 was a randomized, dose-ranging study of ipilimumab 0.3, 3, or 10 mg/kg. Study CA184007 was a randomized, placebo-controlled study of the effect of budesonide on gastrointestinal immune-related adverse events in pts receiving ipilimumab 10 mg/kg. In all studies, ipilimumab was given every 3 weeks (Q3W) × 4 (induction); eligible pts could continue to receive maintenance ipilimumab Q12W from week 24. Pts continue to be followed-up to determine long-term survival.
RESULTS: With a median follow-up ranging from 10.1 to 16.3 months and reaching up to 32.5 months, pts receiving 10 mg/kg ipilimumab showed durable survival; 12- and 18-month survival rates are presented [ Table ]. The tail of the Kaplan-Meier curve flattened at 18 months, indicating that a substantial proportion of patients continued to survive beyond the updated follow-up period in all three studies. Long-term survivors include pts with disease progression (PD) per modified World Health Organization (mWHO) criteria.
CONCLUSIONS: Ipilimumab may result in a long-term survival benefit in pts with advanced melanoma, where 18-month survival rates across 3 Phase II studies range from 34.5% to 39.4% for previously treated pts. These results indicate that more than 1/3 of ipilimumab-treated pts with advanced melanoma experience a long-term survival benefit, including some pts characterized as PD by mWHO. The survival data continue to mature, and follow-up is ongoing. [Table: see text] [Table: see text].
CONCLUSION: As shown by the significant influence of metastatic sites, some P die from their advanced systemic disease situation before they would experience cerebral progression, in part explaining the influence of systemic treatment. In other individuals however, intensified local treatment and systemic treatment appear to influence both cTTP and OS significantly, implicating a direct influence of systemic therapy on BM. This might result from an impaired blood brain barrier around metastatic sites, making sufficient tissue concentrations of cytotoxic agents possible. No significant financial relationships to disclose.
TREATMENT: Rx 375 mg/m(2) IV at day 1; concomitant therapy: Rasburicase, steroids only for anaphylaxis, intrathecal (IT) triple drug at days 1, 3 for CNS pts only. Begin of chemotherapy at day 5. Response evaluation: product of 2 perpendicular diameters of 1 - 3 index lesions/% blasts in BM/PB within 24 h prior to Rx and at day 5: responder (RP): at least 1 lesion with at least objective effect (decrease of ≥25%) and no progress (increase of ≥25 %) at other sites. Study plan: Simon 2-stage phase II with α and β = 5%. Response rate (RR) for poor activity was set to 45%, for good activity 65%. 33 pts entered the first stage, final evaluation after 79 pts.