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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- P aclitaxel. Maeve Lowery MD Memorial Sloan Kettering Cancer Center. Von Hoff et al, NEJM 2013.

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Maeve Lowery MD Memorial Sloan Kettering Cancer Center

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  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

  3. 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.

  4. Modified FOLFIRINOX (MSKCC)

  5. Modified FOLFIRNOX (MSKCC)

  6. 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 …

  7. 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

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

  9. 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] Heinemann et al, Cancer Treatment Reviews, Volume 40, Issue 1, 2014, 118 - 128

  10. Results (N=35) A B

  11. 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…

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