Ipilimumab in the real world: The U.K. expanded access programme (EAP) experience in advanced melanoma.

Abstract

3018 Background: Since publication of the registration trial in 2010 (Hodi et al, NEJM 2010;363:711-23), real world use of ipilimumab (Ipi) in previously treated advanced melanoma patients has extended beyond the specific trial entry criteria of ECOG PS 0-1. We undertook a review of UK patients (pts) treated in the international EAP prior to European licensing of Ipi in August 2011, to compare real world survival outcomes. Methods: UK clinicians registered in the EAP provided anonymised data using pre-specified variable fields for all pts. The EAP stipulated pts should have previously treated, unresectable stage III or IV metastatic melanoma and receive Ipi 3 mg/kg, 3 weekly IV, for up to 4 cycles. Response using RECIST criteria was assessed 12 weekly. Grade ≥3 adverse events (AEs) using CTCAE v3.0 were collected. Results: To date, information on 162 pts has been received from 16 UK sites. Primary sites were: 78% cutaneous, 4% ocular, 1% mucosal, 17% unknown. 78% pts had M1c disease, 14% had brain metastases. No prior therapies ranged from 0-4, 72% pts received 1 prior therapy. Median age was 60 years, men>women (1.6:1). ECOG PS was: 38% 0, 47% 1, 14% 2, 1% 3. BRAF status was known in 38% cases and WT in 75% of these. 19% pts were on steroids at baseline. No cycles delivered was 4 in 52%, 3 in 13%, 2 in 16%, 1 in 17% pts. Most frequent reason for stopping early was clinical evidence of disease progression (71%), death (16%) or unacceptable AE (12%). 32% pts experienced a grade ≥3 AE, the most common being diarrhoea (13%) and fatigue (8%). Complete and partial responses were reported in 1% and 21% of treated pts. At median follow-up of 17 months, median progression free survival and overall survival (OS) were 2.8 and 5.7 months, 1 year OS was 30%. Comparing outcomes of various pt subgroups, the strongest prognostic factor for OS was ECOG PS at the start of treatment (p<0.0001). For pts with PS 0 or 1, median OS was 8.8 months (compared with 10 months in the registration trial). More detailed safety and efficacy data on pt subgroups will be presented. Conclusions: This review, representing the largest Ipi EAP UK dataset, reports overall poorer survival outcomes than in the registration trial, but pts with similar characteristics to the trial population lived longer.

Correlates of response and outcomes with talimogene laherperpvec

“…Impaired functional status, however, had a greater impact of response rates, consistent with prior experience with ipilimumab 21,22 and nivolumab. 23 In theory, TVEC therapy is a suitable treatment for larger tumors.…”

Cost Estimate of Immune-Related Adverse Reactions Associated with Innovative Treatments of Metastatic Melanoma

“…Five articles related to the epidemiological data were clinical trials conducted on patients with phase III or IV unresectable melanoma, who submitted to at least one of the innovative treatments considered in the analysis [3,[5][6][7]9]. The remaining eight articles were retrospective studies [14][15][16][17][18][19][20][21] and a review [22].…”

Head and Neck Squamous Cell Carcinomas Are Characterized by a Stable Immune Signature Within the Primary Tumor Over Time and Space

“…5) and targets of cancer immunotherapy (PDL1/CTLA4; ref. 26). In addition to this, the RPKM of CD3E, GZMA, IFNG, CTLA4, and PDL1 (CD274) are displayed as dot plots ( Supplementary Fig.…”