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 MDMemorial 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, 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]
A B
Results (N=35)
Conclusions
• Gem & nab-P appropriate for 1st 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 1st line therapy in advanced PAC
• It’s good to have options…