Gemcitabine Plus Erlotinib (Ge) Followed By Capecitabine (C) Versus Capecitabine Plus Erlotinib (Ce) Followed By Gemcitabine (G) In Advanced Pancreatic Cancer (Apc): A Randomized, Cross-Over Phase Iii Trial Of The Arbeitsgemeinschaft Internistische Onkologie (Aio)

LBA4011 Background: Gemcitabine plus erlotinib (GE) is regarded as one standard of care for patients (pts) with APC and CE as an all-oral regimen could be a feasible option in this population. To date, the value of a prospectively defined second-line treatment is unclear in APC. Methods: Within a prospective multicenter phase III trial, 281 pts with histologically confirmed APC and adequate organ function were randomly assigned to first-line treatment with either C (2,000 mg/m2/d, d1-14 q3w) plus E (150 mg/d, arm A) or G (1,000 mg/m2 over 30 min weekly x 7, then d1, 8, 15 q4w) plus E (150 mg/d, arm B). In case of treatment-failure (e.g. disease progression or toxicity, TTF1), pts were "crossed-over" to second-line treatment with the comparator cytostatic drug without E. The primary study endpoint was time to treatment failure of second-line therapy (TTF2); secondary endpoints included TTF1, objective response, overall survival (OS) and toxicity. Results: Of 279 eligible pts, 60% were male and median age was 64 years; 47 pts had locally advanced and 232 metastatic disease, 141 pts (51%) received second-line chemotherapy. Objective response rate (CR+PR, ITT) to first-line treatment was 5% (A) vs. 13% (B). Currently, TTF2 is estimated with 4.4 months (mo) in arm A and 4.2 mo in arm B (HR 0.98, p=0.43), median OS is 6.9 mo (A) and 6.6 mo (B), respectively (HR 0.96, p=0.78). TTF1 was significantly prolonged in arm B (2.4 mo vs 3.4 mo; HR 0.69, p=0.0036). Hematological toxicity was more frequent with G-containing regimens, skin rash > grade 1 during E treatment occurred in 31% pts in arm A and in 43% pts in arm B. Tissue tumor samples are available from 204 pts; 123 tumors (70%) harboured a somatic KRAS mutation (mut). Pts with KRAS wildtype (wt, n=53) had an improved OS (wt: 8.0 mo vs. mut: 6.6 mo; HR 1.62, p=0.011). Conclusions: TTF2 and OS were comparable in both arms; GE was superior compared to CE with regard to TTF1. Wt KRAS status was associated with an imprved OS in pts with APC. [Table: see text]