1. 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

2. Von Hoff et al, NEJM 2013

5. 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.

9. Modified FOLFIRINOX (MSKCC)

10. Modified FOLFIRNOX (MSKCC)

11. 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 …

12. 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

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

14. Heinemann et al, Cancer Treatment Reviews, Volume 40, Issue 1, 2014, 118 - 128 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 = 0.0431 [n = 36]

20. AB Results (N=35)

21. 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…