Abstract
272 Molecular prescreening (MP) to treat advanced pancreatic cancer (PC) patients (pts) in early clinical trials Background: Advanced PC has a dismal prognosis, with conventional therapies having poor impact on disease course. The aim of this study was to investigate the impact of a MP program to identify potentially targetable alterations (PTa) in PC pts eligible for clinical trials with matched targeted therapies. Methods: From Jan 2011 to June 2015, a total of 86 chemorefractory PC pts were referred to MP at the VHIO Phase I Unit. Archived tumor samples were analyzed for selected gene mutations (mut) in using mass spectrometry (MassARRAY, Sequenom) until June 2014 or next-generation sequencing (Amplicon, MiSeq) thereafter. PTEN and PDL1 expression levels were measured with immunohistochemistry. All demographic, treatment and survival data were extracted retrospectively from electronic medical records. Results: Median age was 61 years (range 29-78) and 64% were male. Median treatment lines before MP was 2 (range 1-5). Tissue used for MP was primary tumor in 74% and metastatic lesion in 26%. In total, 29% of the samples did not have enough material for mut analysis. The most common PTa were KRAS mut (20/35 with Sequenom, 57%; 22/26 with Amplicon, 85%; p = 0.02), PTEN low (9/22, 41%), PTEN null (4/22, 18%) and CDKN2A mut (2/26, 8%). RNF43 mut, STK11 mut, BRAF V600E and BRAF G469A were found in one sample each. A total of 30 pts were enrolled in Phase I trials following MP, 10 of them with a direct matched therapy (5 with PI3K pathway inh - PTEN low/null, 3 with PI3K + MEK inhibitor - KRAS mut, 1 anti-PDL1 therapy - PDL1 high, 1 HDM2 inh - TP53 wild-type). Partial response was observed in 1 case (PI3K inh + chemotherapy, PTEN null) and stable disease in additional 4 pts (3 with PI3K inh +/- chemotherapy, PTEN low/null; 1 PI3K + MEK inh, KRASmut). Median time on treatment with matched therapy was 2.5 months (CI95% 1.8 – not reached). Conclusions: Genomic/proteomic characterization of PC is able to identify a subpopulation eligible for matched therapy in early clinical trials, with rare cases presenting a clear treatment benefit. Low recruitment can be linked to lack of enough material for MP, low prevalence of PTa and patient characteristics
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