Maeve Lowery MD Memorial Sloan Kettering Cancer Center

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…