Tumor Reduction in Primary and Metastatic Pancreatic Cancer Lesions With nab-Paclitaxel and Gemcitabine: An Exploratory Analysis From a Phase 3 Study
Volker Kunzmann, Ramesh K Ramanathan, David Goldstein, Helen Liu, Stefano Ferrara, Brian Lu, Markus F Renschler, Daniel D Von Hoff, Volker Kunzmann, Ramesh K Ramanathan, David Goldstein, Helen Liu, Stefano Ferrara, Brian Lu, Markus F Renschler, Daniel D Von Hoff
Abstract
Objectives: Results from the phase 3 Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT) led to approval of nab-paclitaxel plus gemcitabine for first-line treatment of metastatic pancreatic cancer. The current analysis evaluated the effects of nab-paclitaxel plus gemcitabine versus gemcitabine on primary pancreatic and metastatic lesions.
Methods: In this analysis of the previously described MPACT trial, changes in pancreatic and metastatic tumor burden were assessed using independently measured diameters of lesions on computed tomography or magnetic resonance imaging scans. Changes in the sums of longest tumor diameters were summarized using descriptive statistics and were included in a multivariate analysis of overall survival.
Results: Primary pancreatic lesion measurement was feasible. Reductions in primary pancreatic tumor burden and metastatic burden from baseline to nadir were significantly greater with nab-paclitaxel plus gemcitabine versus gemcitabine. Baseline pancreatic tumor burden was independently predictive of survival. Both regimens elicited linear reductions in primary pancreatic and metastatic tumor burden through time. There was a high within-patient concordance of tumor changes between primary pancreatic lesions and metastatic lesions.
Conclusions: This analysis of MPACT demonstrated significant tumor shrinkage benefit for nab-paclitaxel plus gemcitabine in both primary pancreatic and metastatic lesions, supporting ongoing evaluation of this regimen in locally advanced disease.
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References
- National Cancer Institute-Surveillance, Epidemiology, and End Results Program. SEER stat fact sheets: pancreas cancer. Available at: . Accessed June 17, 2016.
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.
- Ducreux M, Cuhna AS, Caramella C, et al. Cancer of the pancreas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(suppl 5):v56–v68.
- National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Pancreatic adenocarcinoma. V1. 2016. Available at: . Accessed June 17, 2016.
- American Cancer Society. Cancer facts and figures. 2016. Available at: . Accessed June 17, 2016.
- Heinemann V, Haas M, Boeck S. Neoadjuvant treatment of borderline resectable and non-resectable pancreatic cancer. Ann Oncol. 2013;24:2484–2492.
- Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014;371:2140–2141.
- Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362:1605–1617.
- Hammel P, Huguet F, Van Laethem JL, et al. Comparison of chemoradiotherapy (CRT) and chemotherapy (CT) in patients with a locally advanced pancreatic cancer (LAPC) controlled after 4 months of gemcitabine with or without erlotinib: final results of the international phase III LAP 07 study. J Clin Oncol. 2013;31(suppl):[abstract LBA4003].
- Huguet F, Hammel P, Vernerey D, et al. Impact of chemoradiotherapy (CRT) on local control and time without treatment in patients with locally advanced pancreatic cancer (LAPC) included in the international phase III LAP 07 study. J Clin Oncol. 2014;32(suppl):4001.
- Burris HA, 3rd, Moore MJ, Andersen J, et al. 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;15:2403–2413.
- Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–1825.
- Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–1703.
- Goldstein D, El-Maraghi RH, Hammel P, et al. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J Natl Cancer Inst. 2015;107:dju413.
- Celgene Corporation. Abraxane for Injectable Suspension (Paclitaxel Protein-Bound Particles for Injectable Suspension; Albumin-Bound). Summit, NJ: Celgene Corporation; 2014.
- Tabernero J, Chiorean EG, Infante JR, et al. Prognostic factors of survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer. Oncologist. 2015;20:143–150.
- Vogel A, Penenberg D, McGovern D, et al. Efficacy and safety of nab-paclitaxel (nab-P) plus gemcitabine (gem) vs gem alone in patients (pts) with metastatic pancreatic cancer (MPC) treated to progressive disease (PD) in the phase III MPACT trial. Eur J Cancer. 2015;51(suppl 3):S455.
- Chiorean EG, Wan Y, Whiting S, et al. Impact of nab-paclitaxel (nab-P) plus gemcitabine (G) vs gemcitabine alone on Karnofsky performance status (KPS) in metastatic pancreatic cancer pts with good or poor performance status at baseline: a post-hoc analysis of the MPACT trial. Eur J Cancer. 2015;51(suppl 3):S450.
- Abramson MA, Jazag A, van der Zee JA, et al. The molecular biology of pancreatic cancer. Gastrointest Cancer Res. 2007;1(4 suppl 2):S7–S12.
- Whatcott C, Han H, Posner RG, et al. Tumor-stromal interactions in pancreatic cancer. Crit Rev Oncog. 2013;18:135–151.
- Whatcott CJ, Diep CH, Jiang P, et al. Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer. Clin Cancer Res. 2015;21:3561–3568.
- Philip PA, Lacy J, Dowden SD, et al. LAPACT: An open-label, multicenter phase II trial of nab-paclitaxel (nab-P) plus gemcitabine (Gem) in patients with locally advanced pancreatic cancer (LAPC). J Clin Oncol. 2016;34(suppl):TPS477.
- . Trial to investigate intensified neoadjuvant chemotherapy in locally advanced pancreatic cancer (NEOLAP). Available at: . Accessed February 3, 2016.
Source: PubMed