Aims - The primary aim of this study is to determine the role of radiotherapy in participants with locally advanced pancreatic cancer (LAP). Secondary aims are to evaluate the efficacy and safety of erlotinib.

Background - Adenocarcinoma of the pancreas represents 2% of all cancers and 10 % of gastrointestinal cancers. Approximately 20% of patients present with early disease and are able to undergo curative resection. Forty percent present with advanced loco-regional disease precluding complete resection with a median survival time of 9 – 12 months. The available therapeutic options for patients with locally advanced pancreatic cancer (LAP) are systemic chemotherapy (CT) or chemoradiotherapy (CRT) but the choice of one or other of these regimens remains controversial with conflicting results reported in the literature. The identification of an effective treatment that can achieve durable symptom control remains a high priority for these patients. This study examined several key clinical questions, in particular whether the addition of radiotherapy to standard chemotherapy will increase survival. This study built upon successful studies done in Australia in this area and parallelled an AGITG proposal put to ESPAC previously.

Study Design - LAP07 is a prospective, international, multicentre, phase III randomized study which has two randomization time points. It is led by the French Collaborative research group, GERCOR (Groupe Cooperateur Multidisciplinaire en Oncologie) and aimed to recruit 902 participants internationally from Europe, Canada and Australia, with 60 participants expected from Australia.

Study Progress - LAP07 study was awarded a Cancer Australia grant in January 2009. A total of 18 sites were activated to recruit during 2009-11 and a total of 32 ANZ participants accrued.

Following temporary suspension of recruitment in December 2011, the international Trial Executive Committee (TEC) confirmed their decision to close recruitment in February 2012. Interim results of the trial had been reviewed by the IDSMC, who responded to the TEC that while there were no safety concerns identified, there was also no clear evidence of an advantage of either treatment regimen in R1. The executive of the TMC recommended that recruitment to the trial be ceased on that basis. It was felt that the answer to the R2 question was likely on existing recruitment. All sites were strongly encouraged to continue to randomise patients still eligible to the second or R2 randomisation. Final international R1 recruitment was 442 patients. 270 patients continued onto R2 randomization. There are currently 7 patients from ANZ sites that are in follow up. Data submission is currently in progress and GERCOR anticipate a. further database lock will occur in December 2013.

The LAP07 study has 3 local sub-studies – biological - utilising tissue collected from participants; surgical – examining surgical interventions for both curative purposes and management of symptoms; and radiotherapy quality assurance – ensuring uniformed delivery of trial standard radiotherapy to participants at all sites.

Study Outcomes - From 442 patients included for R1, 269 patients reached R2. After a median follow-up of 36 m, 221 deaths had occurred. Allowing for the interim analyses, in R2 patients the overall survival was 16.5 m [15.5-18.5] and 15.3 m [13.9–17.3] in arms 1 and 2, respectively (HR=1.03 [0.79-1.34], p=0.83). IDMC confirmed that the futility boundary for the hypothesis of CRT superiority was crossed and considered this as the final analysis of the study. In the R1 analysis there was no significant difference in overall survival between gemcitabine and gemcitabine erlotinib. Administrating CRT is not superior to continuing CT in patients with controlled LAPC after 4 months of CT. The use of CRT with this schema is well tolerated, erlotinib is not beneficial in LAPC but increases the toxicity, the OS seen in patients achieving R2 is encouraging of additional strategies. Exploration of subgroups that may have greater benefit is ongoing.

TRANSLATIONAL RESEARCH – donation of FFPE tumour tissue for research is optional.