Clinical Outcomes and Safety of Patients Treated with NAb-Paclitaxel Plus Gemcitabine in Metastatic Pancreatic Cancer: The NAPA Study

Author(s): Martina Catalano, Giandomenico Roviello*, Raffaele Conca, Alberto D’Angelo, Valeria Emma Palmieri, Benedetta Panella, Roberto Petrioli, Anna Ianza, Stefania Nobili, Enrico Mini, Monica Ramello

Journal Name: Current Cancer Drug Targets

Volume 20 , Issue 11 , 2020


  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice.

Methods: From January 2015 to December 2018, patients with metastatic PDAC receiving firstline treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed.

Results: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95% CI; 9-13) and the median progression-free survival (PFS) was 6 months (95% CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients, respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 hematological toxicity frequency was 22.61% for neutropenia, 5.22% for anemia, and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 non-hematological events were reported. Dose reduction was necessary in 51.3% of the patients.

Conclusion: Our results confirm the efficacy and safety of a first-line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.

Keywords: Metastatic pancreatic adenocarcinoma, combined chemotherapy, nab-paclitaxel, gemcitabine, prognostic factor, cancer.

[1]
Maisonneuve, P. Epidemiology and burden of pancreatic cancer. Presse Med., 2019, 48(3 Pt 2), e113-e123.
[http://dx.doi.org/10.1016/j.lpm.2019.02.030] [PMID: 30878335]
[2]
Ferlay, J.; Colombet, M.; Soerjomataram, I.; Dyba, T.; Randi, G.; Bettio, M.; Gavin, A.; Visser, O.; Bray, F. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur. J. Cancer, 2018, 103, 356-387.
[http://dx.doi.org/10.1016/j.ejca.2018.07.005] [PMID: 30100160]
[3]
Bilimoria, K.Y.; Bentrem, D.J.; Ko, C.Y.; Ritchey, J.; Stewart, A.K.; Winchester, D.P.; Talamonti, M.S. Validation of the 6th edition AJCC Pancreatic Cancer Staging System: report from the National Cancer Database. Cancer, 2007, 110(4), 738-744.
[http://dx.doi.org/10.1002/cncr.22852] [PMID: 17580363]
[4]
Vincent, A.; Herman, J.; Schulick, R.; Hruban, R.H.; Goggins, M. Pancreatic cancer. Lancet, 2011, 378(9791), 607-620.
[http://dx.doi.org/10.1016/S0140-6736(10)62307-0] [PMID: 21620466]
[5]
Burris, H.A., III; Moore, M.J.; Andersen, J.; Green, M.R.; Rothenberg, M.L.; Modiano, M.R.; Cripps, M.C.; Portenoy, R.K.; Storniolo, A.M.; Tarassoff, P.; Nelson, R.; Dorr, F.A.; Stephens, C.D.; Von Hoff, D.D. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J. Clin. Oncol., 1997, 15(6), 2403-2413.
[http://dx.doi.org/10.1200/JCO.1997.15.6.2403] [PMID: 9196156]
[6]
Rocha Lima, C.M.; Green, M.R.; Rotche, R.; Miller, W.H., Jr; Jeffrey, G.M.; Cisar, L.A.; Morganti, A.; Orlando, N.; Gruia, G.; Miller, L.L. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J. Clin. Oncol., 2004, 22(18), 3776-3783.
[http://dx.doi.org/10.1200/JCO.2004.12.082] [PMID: 15365074]
[7]
Sultana, A.; Smith, C.T.; Cunningham, D.; Starling, N.; Neoptolemos, J.P.; Ghaneh, P. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J. Clin. Oncol., 2007, 25(18), 2607-2615.
[http://dx.doi.org/10.1200/JCO.2006.09.2551] [PMID: 17577041]
[8]
Heinemann, V.; Quietzsch, D.; Gieseler, F.; Gonnermann, M.; Schönekäs, H.; Rost, A.; Neuhaus, H.; Haag, C.; Clemens, M.; Heinrich, B.; Vehling-Kaiser, U.; Fuchs, M.; Fleckenstein, D.; Gesierich, W.; Uthgenannt, D.; Einsele, H.; Holstege, A.; Hinke, A.; Schalhorn, A.; Wilkowski, R. Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J. Clin. Oncol., 2006, 24(24), 3946-3952.
[http://dx.doi.org/10.1200/JCO.2005.05.1490] [PMID: 16921047]
[9]
Kindler, H.L.; Niedzwiecki, D.; Hollis, D.; Sutherland, S.; Schrag, D.; Hurwitz, H.; Innocenti, F.; Mulcahy, M.F.; O’Reilly, E.; Wozniak, T.F.; Picus, J.; Bhargava, P.; Mayer, R.J.; Schilsky, R.L.; Goldberg, R.M. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J. Clin. Oncol., 2010, 28(22), 3617-3622.
[http://dx.doi.org/10.1200/JCO.2010.28.1386] [PMID: 20606091]
[10]
Conroy, T.; Desseigne, F.; Ychou, M.; Bouché, O.; Guimbaud, R.; Bécouarn, Y.; Adenis, A.; Raoul, J.L.; Gourgou-Bourgade, S.; de la Fouchardière, C.; Bennouna, J.; Bachet, J.B.; Khemissa-Akouz, F.; Péré-Vergé, D.; Delbaldo, C.; Assenat, E.; Chauffert, B.; Michel, P.; Montoto-Grillot, C.; Ducreux, M. Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N. Engl. J. Med., 2011, 364(19), 1817-1825.
[http://dx.doi.org/10.1056/NEJMoa1011923] [PMID: 21561347]
[11]
Von Hoff, D.D.; Ervin, T.; Arena, F.P.; Chiorean, E.G.; Infante, J.; Moore, M.; Seay, T.; Tjulandin, S.A.; Ma, W.W.; Saleh, M.N.; Harris, M.; Reni, M.; Dowden, S.; Laheru, D.; Bahary, N.; Ramanathan, R.K.; Tabernero, J.; Hidalgo, M.; Goldstein, D.; Van Cutsem, E.; Wei, X.; Iglesias, J.; Renschler, M.F. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N. Engl. J. Med., 2013, 369(18), 1691-1703.
[http://dx.doi.org/10.1056/NEJMoa1304369] [PMID: 24131140]
[12]
Sohal, D.P.S.; Mangu, P.B.; Khorana, A.A.; Shah, M.A.; Philip, P.A.; O’Reilly, E.M.; Uronis, H.E.; Ramanathan, R.K.; Crane, C.H.; Engebretson, A.; Ruggiero, J.T.; Copur, M.S.; Lau, M.; Urba, S.; Laheru, D. Metastatic pancreatic cancer: American Society of Clinical Oncology clinical practice guideline. J. Clin. Oncol., 2016, 34(23), 2784-2796.
[http://dx.doi.org/10.1200/JCO.2016.67.1412] [PMID: 27247222]
[13]
Panel NP adenocarcinoma. NCCN Guidelines Pancreatic Adenocarcinoma Gastrointest Oncol, 2019.www.nccn.org
[14]
Eisenhauer, E.A.; Therasse, P.; Bogaerts, J.; Schwartz, L.H.; Sargent, D.; Ford, R.; Dancey, J.; Arbuck, S.; Gwyther, S.; Mooney, M.; Rubinstein, L.; Shankar, L.; Dodd, L.; Kaplan, R.; Lacombe, D.; Verweij, J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer, 2009, 45(2), 228-247.
[http://dx.doi.org/10.1016/j.ejca.2008.10.026] [PMID: 19097774]
[15]
National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. NIH Publ 2009.ctep.cancer.gov
[16]
Frese, K.K.; Neesse, A.; Cook, N.; Bapiro, T.E.; Lolkema, M.P.; Jodrell, D.I.; Tuveson, D.A. nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Discov., 2012, 2(3), 260-269.
[http://dx.doi.org/10.1158/2159-8290.CD-11-0242] [PMID: 22585996]
[17]
De Vita, F.; Ventriglia, J.; Febbraro, A.; Laterza, M.M.; Fabozzi, A.; Savastano, B.; Petrillo, A.; Diana, A.; Giordano, G.; Troiani, T.; Conzo, G.; Galizia, G.; Ciardiello, F.; Orditura, M. NAB-paclitaxel and gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): from clinical trials to clinical practice. BMC Cancer, 2016, 16(1), 709.
[http://dx.doi.org/10.1186/s12885-016-2671-9] [PMID: 27590845]
[18]
Lo Re, G.; Santeufemia, D.A.; Foltran, L.; Bidoli, E.; Basso, S.M.M.; Lumachi, F. Prognostic factors of survival in patients treated with nab-paclitaxel plus gemcitabine regimen for advanced or metastatic pancreatic cancer: a single institutional experience. Oncotarget, 2015, 6(10), 8255-8260.
[http://dx.doi.org/10.18632/oncotarget.3143] [PMID: 25779664]
[19]
Montes, AF; Villarroel, PG; Ayerbes, M; De La Cámara Gómez, J; Aldana, GQ; Tuñas, LV Prognostic and predictive markers of response to treatment in patients with locally advanced unresectable and metastatic pancreatic adenocarcinoma treated with gemcitabine/nab-paclitaxel: Results of a retrospective analysis J Cancer Res Ther, 2017, 13(2), 240-245.
[20]
Papneja, N; Zaidi, A; Chalchal, H; Moser, M; Tan, K; Olson, C Comparisons of Outcomes of Real-World Patients With Advanced Pancreatic Cancer Treated With FOLFIRINOX Versus Gemcitabine and Nab-Paclitaxel: A Population-Based Cohort Study Pancreas, 2019, 48(7), 920-926.
[http://dx.doi.org/10.1097/MPA.0000000000001340]
[21]
Wang, Y.; Camateros, P.; Cheung, W.Y. A Real-World Comparison of FOLFIRINOX, Gemcitabine Plus nab-Paclitaxel, and Gemcitabine in Advanced Pancreatic Cancers. J. Gastrointest. Cancer, 2019, 50(1), 62-68.
[http://dx.doi.org/10.1007/s12029-017-0028-5] [PMID: 29143916]
[22]
Blomstrand, H.; Scheibling, U.; Bratthäll, C.; Green, H.; Elander, N.O. Real world evidence on gemcitabine and nab-paclitaxel combination chemotherapy in advanced pancreatic cancer. BMC Cancer, 2019, 19(1), 40.
[http://dx.doi.org/10.1186/s12885-018-5244-2] [PMID: 30621618]
[23]
Kobayashi, S.; Ueno, M.; Ikeda, M.; Ozaka, M.; Sano, Y.; Hirotani, A.; Tozuka, Y.; Fukushima, T.; Tezuka, S.; Moriya, S.; Umemoto, K.; Watanabe, K.; Sasaki, M.; Hashimoto, Y.; Imaoka, H.; Ohno, I.; Mitsunaga, S.; Yamada, I.; Sasaki, T.; Sasahira, N.; Morimoto, M. A Multicenter Retrospective Study of Gemcitabine Plus Nab-Paclitaxel for Elderly Patients With Advanced Pancreatic Cancer. Pancreas, 2020, 49(2), 187-192.
[http://dx.doi.org/10.1097/MPA.0000000000001484] [PMID: 32011536]
[24]
Walker, E.J.; Ko, A.H. Beyond first-line chemotherapy for advanced pancreatic cancer: an expanding array of therapeutic options? World J. Gastroenterol., 2014, 20(9), 2224-2236.
[http://dx.doi.org/10.3748/wjg.v20.i9.2224] [PMID: 24605022]
[25]
Oettle, H; Riess, H; Stieler, JM; Heil, G; Schwaner, I; Seraphin, J Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: Outcomes from the CONKO-003 Trial J Clin Oncol, 2014, 32(23), 2423-9.
[26]
Kaddis, N.; Saif, M.W. Second-line treatment for pancreatic cancer. JOP, 2014, 15(4), 344-347.
[PMID: 25076339]
[27]
Taieb, J.; Pointet, A.L.; Van Laethem, J.L.; Laquente, B.; Pernot, S.; Lordick, F.; Reni, M. What treatment in 2017 for inoperable pancreatic cancers? Ann. Oncol., 2017, 28(7), 1473-1483.
[http://dx.doi.org/10.1093/annonc/mdx174] [PMID: 28459988]
[28]
Braiteh, F.; Patel, M.B.; Parisi, M.; Ni, Q.; Park, S.; Faria, C. Comparative effectiveness and resource utilization of nab-paclitaxel plus gemcitabine vs FOLFIRINOX or gemcitabine for the first-line treatment of metastatic pancreatic adenocarcinoma in a US community setting. Cancer Manag. Res., 2017, 9, 141-148.
[http://dx.doi.org/10.2147/CMAR.S126073] [PMID: 28461766]
[29]
Scheithauer, W.; Ramanathan, R.K.; Moore, M.; Macarulla, T.; Goldstein, D.; Hammel, P.; Kunzmann, V.; Liu, H.; McGovern, D.; Romano, A.; Von Hoff, D.D. Dose modification and efficacy of nab-paclitaxel plus gemcitabine vs. gemcitabine for patients with metastatic pancreatic cancer: phase III MPACT trial. J. Gastrointest. Oncol., 2016, 7(3), 469-478.
[http://dx.doi.org/10.21037/jgo.2016.01.03] [PMID: 27284481]
[30]
Dell’Aquila, E.; Fulgenzi, C.A.M.; Minelli, A.; Citarella, F.; Stellato, M.; Pantano, F.; Russano, M.; Cursano, M.C.; Napolitano, A.; Zeppola, T.; Vincenzi, B.; Tonini, G.; Santini, D. Prognostic and predictive factors in pancreatic cancer. Oncotarget, 2020, 11(10), 924-941.
[http://dx.doi.org/10.18632/oncotarget.27518] [PMID: 32206189]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 11
Year: 2020
Published on: 18 September, 2020
Page: [887 - 895]
Pages: 9
DOI: 10.2174/1568009620999200918122426
Price: $65

Article Metrics

PDF: 68
HTML: 2