Neoadjuvant imatinib in patients with locally advanced non metastatic GIST in the prospective BFR14 trial

Aurore Blesius, Philippe A Cassier, François Bertucci, Jerome Fayette, Isabelle Ray-Coquard, Binh Bui, Antoine Adenis, Maria Rios, Didier Cupissol, David Pérol, Jean-Yves Blay, Axel Le Cesne, Aurore Blesius, Philippe A Cassier, François Bertucci, Jerome Fayette, Isabelle Ray-Coquard, Binh Bui, Antoine Adenis, Maria Rios, Didier Cupissol, David Pérol, Jean-Yves Blay, Axel Le Cesne

Abstract

Background: The role of surgery in the management of patients with advanced gastrointestinal stromal tumors (GIST) in the era of imatinib mesylate (IM) remains debated. We analyzed the outcome of patients with non metastatic locally advanced primary GIST treated with IM within the prospective BFR14 phase III trial.

Methods: The database of the BFR14 trial was searched for patients with no metastasis at time of inclusion. Patients treated for recurrent disease were excluded. Twenty-five of 434 patients met these criteria.

Results: Fifteen of 25 patients (60%) had a partial response to IM. Nine of the 25 patients (36%) underwent surgical resection of their primary tumor after a median of 7.3 months of IM treatment (range 3.4-12.0). Per protocol patients received continuous IM treatment in the post resection period, in an adjuvant setting. With a median follow-up of 53.5 months, there was a significant improvement in progression-free survival (PFS) and overall survival (OS) for patients who underwent surgical resection versus those who did not (median not reached vs 23.6 months, p = 0.0318 for PFS and median not reached vs 42.2 months, p = 0.0217 for OS). In the group of patients who underwent resection followed by IM, the 3-year PFS and OS rates were 67% and 89% respectively

Conclusions: Following neoadjuvant IM for non metastatic locally advanced GIST 9 of 25 patients (36%) were selected for resection of the primary tumor. OS and PFS figures were close to those of localised intermediate or high risk GIST (70% at 5 years) in the subgroup of operated patients, while the outcome of the non-operated subgroup was similar to that of metastatic GIST.

Figures

Figure 1
Figure 1
Waterfall plot of patients' best response. Dark grey bars represent patients who did not undergo resection of their primary tumor. Light grey bars represent patient who had their primary tumor resected.
Figure 2
Figure 2
Progression-free-survival.
Figure 3
Figure 3
Progression-free survival according to surgical status.
Figure 4
Figure 4
Overall survival according to surgical status.

References

    1. Demetri GD, von MM, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ. et al.Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472–480. doi: 10.1056/NEJMoa020461.
    1. Verweij J, Casali PG, Zalcberg J, Lecesne A, Reichardt P, Blay JY. et al.Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004;364:1127–1134. doi: 10.1016/S0140-6736(04)17098-0.
    1. Cassier PA, Dufresne A, Arifi S, El SH, Labidi I, Ray-Coquard I. et al.Imatinib mesilate for the treatment of gastrointestinal stromal tumour. Expert Opin Pharmacother. 2008;9:1211–1222. doi: 10.1517/14656566.9.7.1211.
    1. Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S. et al.Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–580. doi: 10.1126/science.279.5350.577.
    1. Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N. et al.PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708–710. doi: 10.1126/science.1079666.
    1. Demetri GD, Benjamin RS, Blanke CD, Blay JY, Casali P, Choi H. et al.NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)--update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw. 2007;5(Suppl 2):S1–29. quiz S30.
    1. Casali PG, Jost L, Reichardt P, Schlemmer M, Blay JY. Gastrointestinal stromal tumors: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2008;19(Suppl 2):ii35–ii38. doi: 10.1093/annonc/mdn080.
    1. Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD. et al.Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373:1097–1104. doi: 10.1016/S0140-6736(09)60500-6.
    1. Andtbacka RH, Ng CS, Scaife CL, Cormier JN, Hunt KK, Pisters PW. et al.Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol. 2007;14:14–24. doi: 10.1245/s10434-006-9034-8.
    1. Bonvalot S, Eldweny H, Pechoux CL, Vanel D, Terrier P, Cavalcanti A. et al.Impact of surgery on advanced gastrointestinal stromal tumors (GIST) in the imatinib era. Ann Surg Oncol. 2006;13:1596–1603. doi: 10.1245/s10434-006-9047-3.
    1. Eisenberg BL, Harris J, Blanke CD, Demetri GD, Heinrich MC, Watson JC. et al.Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2009;99:42–47. doi: 10.1002/jso.21160.
    1. Gronchi A, Fiore M, Miselli F, Lagonigro MS, Coco P, Messina A. et al.Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg. 2007;245:341–346. doi: 10.1097/01.sla.0000242710.36384.1b.
    1. Raut CP, Posner M, Desai J, Morgan JA, George S, Zahrieh D. et al.Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. 2006;24:2325–2331. doi: 10.1200/JCO.2005.05.3439.
    1. Rutkowski P, Nowecki Z, Nyckowski P, Dziewirski W, Grzesiakowska U, Nasierowska-Guttmejer A. et al.Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate. J Surg Oncol. 2006;93:304–311. doi: 10.1002/jso.20466.
    1. Blay JY, Le CA, Ray-Coquard I, Bui B, Duffaud F, Delbaldo C. et al.Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol. 2007;25:1107–1113. doi: 10.1200/JCO.2006.09.0183.
    1. Le Cesne A, Ray-Coquard I, Bui B, Rios M, Adenis A, Bertucci F. et al.Continuous versus interruption of imatinib (IM) in responding patients with advanced GIST after three years of treatment: A prospective randomized phase III trial of the French Sarcoma Group. J Clin Oncol (Meeting Abstracts) 2007;25:10005.
    1. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L. et al.New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–216. doi: 10.1093/jnci/92.3.205.
    1. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–481. doi: 10.2307/2281868.

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