On this episode of the SO files, we interview Dr. Andrea Wang-Gillam MD/PhD, associate professor in the division of oncology at Wash U School of medicine and clinical director of the GI oncology, about systemic options for treating pancreatic adenocarcinoma. As much as we all love a good Whipple, this really is a systemic disease, and unlike other cancers 100% of patients regardless of stage will need some form of systemic treatment. Good thing we have great options to choose from! …Right?
RCTs in the metastatic setting
Daniel D. Von Hoff, M.D., Thomas Ervin, M.D., Francis P. Arena, M.D., E. Gabriela Chiorean, M.D., Jeffrey Infante, M.D., Malcolm Moore, M.D., Thomas Seay, M.D., Sergei A. Tjulandin, M.D., Wen Wee Ma, M.D., Mansoor N. Saleh, M.D., Marion Harris, M.D., Michele Reni, M.D., Scot Dowden, M.D., Daniel Laheru, M.D., Nathan Bahary, M.D., Ramesh K. Ramanathan, M.D., Josep Tabernero, M.D., Manuel Hidalgo, M.D., Ph.D., David Goldstein, M.D., Eric Van Cutsem, M.D., Xinyu Wei, Ph.D., Jose Iglesias, M.D., and Markus F. Renschler, M.D.
Take away: nab-Paclitaxel (Abraxane) added to gemcitabine improved survival when compared to gemcitabine alone (median OS 8.5 pos vs 6.7 mos, ORR 23% vs 7%).
Thierry Conroy, M.D., Françoise Desseigne, M.D., Marc Ychou, M.D., Ph.D., Olivier Bouché, M.D., Ph.D., Rosine Guimbaud, M.D., Ph.D., Yves Bécouarn, M.D., Antoine Adenis, M.D., Ph.D., Jean-Luc Raoul, M.D., Ph.D., Sophie Gourgou-Bourgade, M.Sc., Christelle de la Fouchardière, M.D., Jaafar Bennouna, M.D., Ph.D., Jean-Baptiste Bachet, M.D., Faiza Khemissa-Akouz, M.D., Denis Péré-Vergé, M.D., Catherine Delbaldo, M.D., Eric Assenat, M.D., Ph.D., Bruno Chauffert, M.D., Ph.D., Pierre Michel, M.D., Ph.D., Christine Montoto-Grillot, M.Chem., and Michel Ducreux, M.D., Ph.D. for the Groupe Tumeurs Digestives of Unicancer and the PRODIGE Intergroup
FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, fluorouracil) is a much more effective regimen than gemcitabine alone (median OS 11.1 mos vs 6.8 mos; ORR 32% vs 9%), but is a more toxic regimen with higher rate of adverse events.
RCTS in the Adjuvant Setting
Take away: 6 months of gemcitabine treatment after complete resection was better for OS than no treatment (13.4 mos vs 6.7 mos).
Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O’Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW; European Study Group for Pancreatic Cancer.
Take away: Combination gemcitabine and capecitabine (Xeloda) did better than gemcitabine alone in patients with completely resected disease (OS 28 mos v 25.5 pos).
New and exciting things coming down the pipeline…
1. Targeting desmoplastic reaction
Hingorani SR, Zheng L, Bullock AJ, Seery TE, Harris WP, Sigal DS, Braiteh F, Ritch PS, Zalupski MM, Bahary N, Oberstein PE, Wang-Gillam A, Wu W, Chondros D, Jiang P, Khelifa S, Pu J, Aldrich C, Hendifar AE.
Take away: The addition of PEGPH20 (pegvorhyaluronidase alfa) to gem/abraxane improved PFS and OS compared to gem/abraxane alone in patients with untreated metastatic disease, especially in patients with hyaluron high tumors. Phase III study ongoing!!
2. Targeting cancer stem cells
Ongoing phase Ib dose escalation study of BBI608 (Napabucasin), STAT3/cancer stem cell inhibitor, in combination with other standard chemotherapy regimens (gem/abraxane, FOLFIRINOX, FOLFIRI). Accrual slated to complete June 2018.
3. Targeting innate immunity
Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial.
Lancet Onc. 2016
Nywening TM, Wang-Gillam A, Sanford DE, Belt BA, Panni RZ, Cusworth BM, Toriola AT, Nieman RK, Worley LA, Yano M, Fowler KJ, Lockhart AC, Suresh R, Tan BR, Lim KH, Fields RC, Strasberg SM, Hawkins WG, DeNardo DG, Goedegebuure SP, Linehan DC.
Blockade of CCR2, as a means to suppress tumor infiltration of immunosuppressive tumor associated macrophages, in combination with FOLFIRINOX chemotherapy for borderline resectable or locally advanced PDAC resulted in a 49% objective tumor response rate.
CCR2 inhibition decreases tumor-associated macrophages and Treg cells, and increases CD8+ and CD4+ T cells in pancreatic tumors. In preliminary data presented at ASCO, CX872-B plus FOLFIRINOX resulted in a TCR of 78% and an ORR of 30 to 37% with no safety issues ascribed to CCX872-B use. Estimated study completion date December 2018.