Objective AIO-PK0104 investigated two treatment strategies in advanced pancreatic cancer (PC): a reference sequence of gemcitabine/erlotinib followed by 2nd-line capecitabine was compared with a reverse experimental sequence of capecitabine/erlotinib followed by gemcitabine.
Methods 281 patients with PC were randomly assigned to 1st-line treatment with either gemcitabine plus erlotinib or capecitabine plus erlotinib. In case of treatment failure (eg, disease progression or toxicity), patients were allocated to 2nd-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was time to treatment failure (TTF) after 1st- and 2nd-line therapy (TTF2; non-inferiority design). KRAS exon 2 mutations were analysed in archival tumour tissue from 173 of the randomised patients.
Results Of the 274 eligible patients, 43 had locally advanced and 231 had metastatic disease; 140 (51%) received 2nd-line chemotherapy. Median TTF2 was estimated with 4.2 months in both arms; median overall survival was 6.2 months with gemcitabine/erlotinib followed by capecitabine and 6.9 months with capecitabine/erlotinib followed by gemcitabine, respectively (HR 1.02, p=0.90). TTF for 1st-line therapy (TTF1) was significantly prolonged with gemcitabine/erlotinib compared to capecitabine/erlotinib (3.2 vs 2.2 months; HR 0.69, p=0.0034). Skin rash was associated with both TTF2 (rash grade 0/1/2–4:2.9/4.3/6.7 months, p<0.0001) and survival (3.4/7.0/9.6 months, p<0.0001). Each arm showed a safe and manageable toxicity profile during 1st- and 2nd-line therapy. A KRAS wild-type status (52/173 patients, 30%) was associated with an improved overall survival (HR 1.68, p=0.005).
Conclusion Both treatment strategies are feasible and demonstrated comparable efficacy; KRAS may serve as biomarker in patients with advanced PC treated with erlotinib.
Trial registration number This study was registered at ClinicalTrials.gov, number NCT00440167.
- pancreatic cancer
- pancreatic cancer
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Previous presentation 46th ASCO Annual Meeting, 4–8 June, 2010, Chicago, IL and 35th ESMO Congress, 8–12 October, 2010, Milan, Italy.
Funding This work was supported by Hoffmann-La Roche, Germany.
Competing interests VH: Roche (consultant, honoraria for scientific presentations, research funding). UV-K: none. DW: none. EK: none. AM: none. CW: none. SK: none. GK: none. TCG: none. LFvW: none. MRC: Roche (honoraria for scientific presentations, research funding, travel grants). MG: none. TFG: none. SH-B: none. OR: none. GB: none. TH: none. YDK: none. AJ: none. SN: none. SB: Roche (honoraria for scientific presentations, research funding, travel grants).
Ethics approval This study was conducted with the approval of the ethics committee of the Ludwig-Maximilians University of Munich, Germany.
Provenance and peer review Not commissioned; externally peer reviewed.