What would you recommend as first line therapy for a 68 y/o woman with advanced pancreatic cancer and limited metastatic disease with ECOG-1? Gemcitabine plus nab-Paclitaxel Maeve Lowery MD Memorial Sloan Kettering Cancer Center

Von Hoff et al, NEJM 2013

Updated MPACT Results GI ASCO 2014 Median overall survival remained significantly longer on combination arm 4% of patient on gem-nab-P arm alive at 3 years, none in gem arm Prespecified subgroups: KPS, age, presence of liver met, elevated Ca 19.9 associated with worse outcomes, Combination therapy reduced negative survival association of elevated Ca 19.9 (homogeneity of biliary decompression not known) No grade 4 neuropathy, 17% grade 3 median time to improvements 29 days, half could resume treatment.

Modified FOLFIRINOX (MSKCC)

Modified FOLFIRNOX (MSKCC)

How Can We Compare the Data? Trial enrolled different patient populations (older pts, ECOG 2 included in MPACT) MPACT trial performed in both community and academic centers, USA, Europe and Australia – results are more broadly applicable in variety of clinical settings We just know both combinations are more effective than Gemcitabine …

Why Gem & nab-P? Toxicity profile (less febrile neutropenia, neuropathy reversible) More likely to be given in combination with experimental therapy Limited metastatic disease, ECOG 1 No mediport In practice, FOLFIRINOX is given as a modified regimen in US academic centers

Is there a Better Way to Select Therapy? Clinical characteristics Blood biomarkers – CTCs – Pharmacogenomic profiling – cfDNA Tissue biomarkers – Genotyping – Protein expression

Heinemann et al, Cancer Treatment Reviews, Volume 40, Issue 1, 2014, SPARC Expression as Biomarker of Response to Gem & nab-P Phase I/II study, high SPARC expression was associated with a significantly longer OS vs. low SPARC expression Median OS 17.8 vs. 8.1 months; p = [n = 36]

AB Results (N=35)

Conclusions Gem & nab-P appropriate for 1 st line therapy, especially in ECOG 1, limited disease burden Where possible, patients will eventually receive both treatments in sequence We need better predictive biomarkers to select 1 st line therapy in advanced PAC It’s good to have options…