No abstract

In this prospective phase III trial, afatinib combined with paclitaxel improved progression-free survival and objective response, compared with single-agent chemotherapy, in patients with NSCLC who were clinically enriched for ErbB dependency having failed platinum-based chemotherapy, gefitinib/erlotinib and afatinib monotherapy after initial benefit on each tyrosine kinase inhibitor.

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.

Before licensing, ipilimumab was first made available to previously treated advanced melanoma patients through an expanded access programme (EAP) across Europe. We interrogated data from UK EAP patients to inform future clinical practice. Clinicians registered in the UK EAP provided anonymized patient data using a prespecified variable fields datasheet. Data collected were baseline patient characteristics, treatment delivered, toxicity, response, progression-free survival and overall survival (OS). Data were received for 193 previously treated metastatic melanoma patients, whose primary sites were cutaneous (82%), uveal (8%), mucosal (2%), acral (3%) or unknown (5%). At baseline, 88% of patients had a performance status (PS) of 0–1 and 20% had brain metastases. Of the patients, 53% received all four planned cycles of ipilimumab; the most common reason for stopping early was disease progression, including death from melanoma. Toxicity was recorded for 171 patients, 30% of whom experienced an adverse event of grade 3 or higher, the most common being diarrhoea (13%) and fatigue (9%). At a median follow-up of 23 months, the median progression-free survival and OS were 2.8 and 6.1 months, respectively; the 1-year and 2-year OS rates were 31 and 14.8%, respectively. The 2-year OS was significantly lower for patients with poorer PS (P<0.0001), low albumin concentrations (P<0.0001), the presence of brain metastases (P=0.007) and lactate dehydrogenase levels more than two times the upper limit of normal (P<0.0001) at baseline. These baseline characteristics are negative predictors of benefit from ipilimumab and should be taken into consideration before prescription.