Tumor growth rate as a metric of progression, response, and prognosis in pancreatic and intestinal neuroendocrine tumors

Clarisse Dromain, Marianne E. Pavel, Philippe Ruszniewski, Alison Langley, Christine Massien, Eric Baudin, Martyn E. Caplin, Austria M. Raderer, Belgium I. Borbath, D. Ysebaert, E. Sedláčková, P. Vítek, Denmark H. Grønbæk, France A. Adenis, L. Buscail, G. Cadiot, S. Dominguez, M. Ducreux, C. Lombard-Bohas, E. MitryP. Ruszniewski, J. F. Seitz, N. Begum, I. Harsch, M. Pavel, C. Schöfl, M. Weber, B. Wiedenmann, M. Mallath, P. Patil, K. Sambasivaiah, R. Saxena, E. Bajetta, A. Buonadonna, R. Buzzoni, R. Cannizzaro, A. Colao, C. De Angelis, P. Tomassetti, J. Ćwikła, B. Kos-Kudła, Slovakia T. Salek, J. Capdevila, G. Soler, J. M. Tabernero, H. Ahlman, M. Kjellman, G. Aithal, A. Anthoney, M. Caplin, A. Grossman, J. Newell-Price, J. Ramage, N. Reed, A. Rees, W. Steward, L. Wall, M. Choti, A. T. Phan, E. M. Wolin

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background: Lanreotide depot/autogel antitumor activity in intestinal/pancreatic neuroendocrine tumors (NETs) was demonstrated in the phase-3 CLARINET study (NCT00353496), based on significantly prolonged progression-free survival (PFS) versus placebo. Methods: During CLARINET, patients with metastatic intestinal/pancreatic NETs received lanreotide depot/autogel 120 mg or placebo every 4 weeks for 96 weeks. Imaging data (response evaluation criteria in solid tumors [RECIST] v1.0, centrally reviewed) were re-evaluated in this post hoc analysis of tumor growth rate (TGR) in NETs. TGR (%/month) was calculated from two imaging scans during relevant periods: pre-treatment (TGR 0 ); 12-24 weeks before randomization versus baseline; each treatment visit versus baseline (TGR Tx-0 ); between consecutive treatment visits (TGR Tx-Tx ). To assess TGR as a measure of prognosis, PFS was compared for TGR 0 subgroups stratified by optimum TGR 0 cut-off; a multivariate analysis was conducted to identify prognostic factors for PFS. Results: TGR 0 revealed tumors growing during pre-treatment (median [interquartile range] TGR 0 : lanreotide 2.1%/month [0.2; 6.1]; placebo 2.7%/month [0.15; 6.8]), contrary to RECIST status. TGR was significantly reduced by 12 weeks with lanreotide versus placebo (difference in least-square mean TGR 0-12 of - 2.9 [- 5.1, - 0.8], p = 0.008), a difference that was maintained at most subsequent visits. TGR 0 > 4%/month had greater risk of progression/death than ≤4%/month (hazard ratio 4.1; [95% CI 2.5-6.5]; p < 0.001); multivariate analysis revealed lanreotide treatment, progression at baseline, TGR 0 , hepatic tumor load, and primary tumor type were independently associated with PFS. Conclusions: TGR provides valuable information on tumor activity and prognosis in patients with metastatic intestinal/pancreatic NETs, and identifies early lanreotide depot/autogel antitumor activity. Trial registration: Retrospective registration, 18 July 2006; EudraCT: 2005-004904-35; ClinicalTrials.gov: NCT00353496.

Original languageEnglish (US)
Article number66
JournalBMC Cancer
Volume19
Issue number1
DOIs
StatePublished - Jan 14 2019

Keywords

  • Lanreotide
  • Neuroendocrine tumor
  • Prognostic factor
  • RECIST
  • Tumor growth rate

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

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    Dromain, C., Pavel, M. E., Ruszniewski, P., Langley, A., Massien, C., Baudin, E., Caplin, M. E., Raderer, A. M., Borbath, B. I., Ysebaert, D., Sedláčková, E., Vítek, P., Grønbæk, D. H., Adenis, F. A., Buscail, L., Cadiot, G., Dominguez, S., Ducreux, M., Lombard-Bohas, C., ... Wolin, E. M. (2019). Tumor growth rate as a metric of progression, response, and prognosis in pancreatic and intestinal neuroendocrine tumors. BMC Cancer, 19(1), [66]. https://doi.org/10.1186/s12885-018-5257-x