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- Title
Imatinib and everolimus in patients with progressing advanced chordoma: A phase 2 clinical study.
- Authors
Stacchiotti, Silvia; Morosi, Carlo; Lo Vullo, Salvatore; Casale, Alessandra; Palassini, Elena; Frezza, Anna Maria; Dinoi, Gabriella; Messina, Antonella; Gronchi, Alessandro; Cavalleri, Adalberto; Venturelli, Elisabetta; Morelli, Daniele; Pilotti, Silvana; Collini, Paola; Brich, Silvia; Tamborini, Elena; Mariani, Luigi; Casali, Paolo G.
- Abstract
<bold>Background: </bold>We present the results of an academic phase 2 study on imatinib plus everolimus in patients who have progressive advanced chordoma.<bold>Methods: </bold>In January 2011, 43 adult chordoma patients were enrolled in the study and received imatinib 400 mg/day and everolimus 2.5 mg/day until progression or limiting toxicity. Eligible patients had progressed in the 6 months before study entry. PDGFRB, S6, and 4EBP1 expression and phosphorylation were evaluated by way of immunohistochemistry and/or western blotting. The primary endpoint was the overall response rate (ORR) according to Choi criteria. Secondary endpoints were RECIST 1.1 response, progression-free survival (PFS), overall survival (OS), correlation between S6/4EBP1 phosphorylation and response.<bold>Results: </bold>Thirteen of 43 patients were pretreated with imatinib. Among 40 of the 43 patients who were evaluable by Choi criteria, the best responses were 9 with partial response (ORR, 20.9%), 24 with stable disease (SD) (ORR, 55.8%), and 7 with progressive disease (ORR, 16.3%). Forty-two patients were evaluable by RECIST criteria, with 1 partial response (ORR, 2.3%), 37 stable disease (ORR, 86%), and 4 progressive disease (ORR, 9.3%). The median PFS according to Choi criteria was 11.5 months (range, 4.6-17.6 months), and 58.8% and 48.1% of patients were progression-free at 9 and 12 months, respectively. The median PFS by RECIST criteria was 14 months; the median OS was 47.1 months. When assessable, S6/4EBP1 was phosphorylated in a high and moderate/low proportion of tumor cells in responsive and nonresponsive patients, respectively. Toxicity caused a temporary and definitive treatment discontinuation in 60.5% and 30.2% of patients, respectively.<bold>Conclusions: </bold>Imatinib plus everolimus showed a limited activity in progressing advanced chordoma. Interestingly, the amount of tumor cells activated for mammalian target of rapamycin effectors correlated with the response. Toxicity was not negligible.
- Subjects
CHORDOMA; EVEROLIMUS; IMATINIB; COMBINATION drug therapy; DISEASE progression
- Publication
Cancer (0008543X), 2018, Vol 124, Issue 20, p4056
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.31685