Initial systemic chemotherapy ( 6 months ) with a combination regimen is recommended for most patients ( for some patients radiation therapy may be offered up front ) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile .
There is no clear evidence to support one regimen over another .
PURPOSE To provide evidence -based recommendations to oncologists and others for treatment of patients with locally advanced , unresectable pancreatic cancer .
Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the ‘Arbeitsgemeinschaft Internistische Onkologie’ (AIO-PK0104)
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 r and omly 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 r and omised 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 Clinical Trials.gov , number NCT00440167 . Significance of this study What is already known on this subject ? Gemcitabine-based chemotherapy remains an international st and ard of care for patients with non-resectable , advanced pancreatic cancer ( PC ) .  Anti-EGFR treatment with the tyrosine kinase inhibitor erlotinib , as well as chemotherapy intensification by application of the FOLFIRINOX regimen , both significantly improved overall survival in r and omised phase 3 trials . The optimal ( sequential ) regimen for the use of gemcitabine , erlotinib and the oral fluoropyrimidine capecitabine remains unclear in advanced PC . Molecular predictors for the efficacy of anti-EGFR treatments in PC have not been defined up to now . What are the new findings ? The sequential use of gemcitabine , erlotinib and capecitabine is safe and equally effective in PC ; gemcitabine appears to be more effective in 1st- and 2nd-line therapy than capecitabine and therefore remains the preferred combination partner for erlotinib .  Skin rash is strongly correlated with efficacy outcome measures in PC patients treated with erlotinib . KRAS wild-type status appears to be associated with improved overall survival in patients treated with erlotinib in this AIO study . Significance of this study How might it impact on clinical practice in the foreseeable future ? The benefit of adding erlotinib to chemotherapy is restricted to patients that experience skin rash during treatment ; non-rash patients are characterised by a very poor outcome and need to be offered novel treatment strategies . Second-line salvage chemotherapy is effective and safe in selected PC patients . KRAS could serve as the first biomarker for improved survival in erlotinib-treated patients ; the predictive value of KRAS for erlotinib efficacy remains to be defined prospect ively
Initial systemic chemotherapy ( 6 months ) with a combination regimen is recommended for most patients ( for some patients radiation therapy may be offered up front ) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile .
There is no clear evidence to support one regimen over another .
PURPOSE To provide evidence -based recommendations to oncologists and others for treatment of patients with locally advanced , unresectable pancreatic cancer .