Long-term outcome and effect of maintenance therapy in patients with advanced sarcoma treated with trabectedin: an analysis of 181 patients of the French ATU compassionate use program

Jean-Yves Blay, Antoine Italiano, Isabelle Ray-Coquard, Axel Le Cesne, Florence Duffaud, Maria Rios, Olivier Collard, François Bertucci, Emmanuelle Bompas, Nicolas Isambert, Loic Chaigneau, Philippe Cassier, Binh Bui, Gauthier Decanter, Olfa Derbel, Jean-Michel Coindre, Patrick Zintl, Nadia Badri, Nicolas Penel, Jean-Yves Blay, Antoine Italiano, Isabelle Ray-Coquard, Axel Le Cesne, Florence Duffaud, Maria Rios, Olivier Collard, François Bertucci, Emmanuelle Bompas, Nicolas Isambert, Loic Chaigneau, Philippe Cassier, Binh Bui, Gauthier Decanter, Olfa Derbel, Jean-Michel Coindre, Patrick Zintl, Nadia Badri, Nicolas Penel

Abstract

Background: The long term outcome of advanced sarcoma patients treated with trabectedin outside of clinical trials and the utility of maintenance treatment has not been reported.

Methods: Between 2003 and 2008, patients with advanced sarcoma failing doxorubicin could be treated within a compassionate use program (ATU, Temporary Use Authorization) of trabectedin in France using the standard 3-weekly regimen. Data from 181 patients (55%) were collected from 11 centres and analyzed.

Results: Trabectedin was given in first, second, third or fourth line in metastatic phase in 6%, 37%, 33% and 23% of patients respectively. With a median follow-up of 6 years, median PFS and OS were 3.6 months and 16.1 months respectively. The median number of cycles was 3 (range 1-19). Best response were partial response (PR, n = 18, 10%), stable disease (SD, n = 69, 39%) and progressive disease (PD, n = 83, 46%), non evaluable (NE, n = 9, 5%). Thirty patients (17%) had to be hospitalized for treatment- related side effects. Independent prognostic factors in multivariate analysis (Cox model) were myxoid LPS and line of trabectedin for PFS, and myxoid LPS and retroperitoneal sarcomas for OS. Patients in PR or SD after 6 cycles continuing treatment had a better PFS (median 5.3 vs 10.5 months, p = 0.001) and OS (median 13.9 vs 33.4 months, p = 0.009) as compared to patients who stopped after 6 cycles.

Conclusions: In this compassionate use program, trabectedin yielded similar or better PFS and OS than in clinical trials. Maintenance treatment beyond 6 cycles was associated with an improved survival.

Figures

Figure 1
Figure 1
Progression-free and overall survival of the cohort according to the number of lines. A: Progression-free survival in the whole cohort. B: Progression-free survival of patients treated in first (blue), second (green), third (light brown) or >3 (purple) line of treatment (log-rank, p = 0,043). C: Overall survival in the whole cohort. D: Overall survival of patients treated in first (blue), second (green), third (light brown) or >3 (purple) line of treatment (logrank, p = 0,018).
Figure 2
Figure 2
Overall survival according to the best response to trabectedin. Overall survival of patients whose best response was: partial response (light brown), stable disease (purple), progressive disease (green), or non evaluable (blue). Log-rank p value, p < 0,0001.
Figure 3
Figure 3
Progression-free and overall survival according to maintenance after 6 cycles. No maintenance- treatment interruption after 6 cycles (blue); maintenance- treatment beyond 6 cycles (green). Log-rank p-value for PFS, p = 0,007; Log-rank for OS, p = 0,0002.

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