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The off-label use of targeted therapies in sarcomas: the OUTC'S program.

Eberst L, Cropet C, Le Cesne A, Pautier P, Penel N, Adenis A, Chevreau C, Bay JO, Collard O, Cupissol D, Duffaud F, Gentet JC, Piperno-Neumann S, Marec-Berard P, Bompas E, Thyss A, Chaigneau L, Cassier P, Bertucci F, Blay JY, Ray-Coquard I - BMC Cancer (2014)

Bottom Line: The median progression-free survival was 4,1 months (IC 95% [3,2-4,8]).Three complete responses were observed.No toxic death occurred, grade 3 and 4 toxicities were reported in 74 (27%) and 14 patients (5%) respectively.

View Article: PubMed Central - PubMed

Affiliation: Centre Léon Bérard, 28 rue Laennec 69 373, LYON CEDEX 08, France. isabelle.ray-coquard@lyon.unicancer.fr.

ABSTRACT

Background: Few targeted therapies (TTs) are registered for sarcoma treatment despite numerous phase II studies and yet there are potential treatment options for patients after standard treatment escape. The French Sarcoma Group - Bone Tumor Study Group (GSF-GETO) created a national registry to evaluate the outcome of patients treated with off-label TTs.

Methods: Every consecutive sarcoma-patient receiving an off-label TT outside a clinical trial was included. The objective was to describe this patient efficacy and safety data in routine practice.

Results: From October 2008 to October 2011, 249 patients in 24 centers received 278 treatment lines with TTs. Twenty-five histological subtypes were included: most frequent were leiomyosarcoma (n=48, receiving sorafenib in 63%, and sunitinib in 27%), GIST (n=39, receiving sorafenib in 79%), and angiosarcoma (n=18, receiving sorafenib in 78%). The overall response rate to TTs was 15% (95% CI [10,6-20,2]), the disease control rate at 2 months was 59%. The median progression-free survival was 4,1 months (IC 95% [3,2-4,8]). Three complete responses were observed. No toxic death occurred, grade 3 and 4 toxicities were reported in 74 (27%) and 14 patients (5%) respectively.

Conclusion: Off-label TTs can be used for sarcoma patients in routine practice with an acceptable toxicity profile and efficacy similar to that reported in non-randomized clinical trials.

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Related in: MedlinePlus

Progression-free survival data. A. Progression-free survival for soft-tissue sarcoma (except GIST). B: Progression-free survival of the patients in third line and after (number of previous chemotherapy >2). C: Progression-free survival of the GIST group. D: Progression-free survival of the leiomyosarcoma group.
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Fig1: Progression-free survival data. A. Progression-free survival for soft-tissue sarcoma (except GIST). B: Progression-free survival of the patients in third line and after (number of previous chemotherapy >2). C: Progression-free survival of the GIST group. D: Progression-free survival of the leiomyosarcoma group.

Mentions: Median follow-up since diagnosis was five years (range: 0,1 to 32,9, n = 234, 14 patients without follow-up data and one patient with missing date of diagnosis). The median PFS of the entire series was 4,1 months (95% CI [3,2-4,8]). For STS (Figure 1A), median PFS was 3,8 months (95% CI [2,4,9]). Figure 1B shows the PFS of patients treated with TTs in third line and beyond. GIST and LMS, the most two frequent subtypes, had a median PFS of 5,5 months (95% CI [4,4-8,1]) and 2,9 months (95% CI [2,1-4,6]) respectively (Figure 1C and D). Forty-eight patients died (20%), of underlying cancer in 98% of cases (47 patients). One patient died from a massive pulmonary embolism during treatment with sunitinib, in the context of an intra-cardiac metastasis of a high-grade undifferentiated thoracic sarcoma (this event was not attributed to sunitinib by the investigator).Figure 1


The off-label use of targeted therapies in sarcomas: the OUTC'S program.

Eberst L, Cropet C, Le Cesne A, Pautier P, Penel N, Adenis A, Chevreau C, Bay JO, Collard O, Cupissol D, Duffaud F, Gentet JC, Piperno-Neumann S, Marec-Berard P, Bompas E, Thyss A, Chaigneau L, Cassier P, Bertucci F, Blay JY, Ray-Coquard I - BMC Cancer (2014)

Progression-free survival data. A. Progression-free survival for soft-tissue sarcoma (except GIST). B: Progression-free survival of the patients in third line and after (number of previous chemotherapy >2). C: Progression-free survival of the GIST group. D: Progression-free survival of the leiomyosarcoma group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4289372&req=5

Fig1: Progression-free survival data. A. Progression-free survival for soft-tissue sarcoma (except GIST). B: Progression-free survival of the patients in third line and after (number of previous chemotherapy >2). C: Progression-free survival of the GIST group. D: Progression-free survival of the leiomyosarcoma group.
Mentions: Median follow-up since diagnosis was five years (range: 0,1 to 32,9, n = 234, 14 patients without follow-up data and one patient with missing date of diagnosis). The median PFS of the entire series was 4,1 months (95% CI [3,2-4,8]). For STS (Figure 1A), median PFS was 3,8 months (95% CI [2,4,9]). Figure 1B shows the PFS of patients treated with TTs in third line and beyond. GIST and LMS, the most two frequent subtypes, had a median PFS of 5,5 months (95% CI [4,4-8,1]) and 2,9 months (95% CI [2,1-4,6]) respectively (Figure 1C and D). Forty-eight patients died (20%), of underlying cancer in 98% of cases (47 patients). One patient died from a massive pulmonary embolism during treatment with sunitinib, in the context of an intra-cardiac metastasis of a high-grade undifferentiated thoracic sarcoma (this event was not attributed to sunitinib by the investigator).Figure 1

Bottom Line: The median progression-free survival was 4,1 months (IC 95% [3,2-4,8]).Three complete responses were observed.No toxic death occurred, grade 3 and 4 toxicities were reported in 74 (27%) and 14 patients (5%) respectively.

View Article: PubMed Central - PubMed

Affiliation: Centre Léon Bérard, 28 rue Laennec 69 373, LYON CEDEX 08, France. isabelle.ray-coquard@lyon.unicancer.fr.

ABSTRACT

Background: Few targeted therapies (TTs) are registered for sarcoma treatment despite numerous phase II studies and yet there are potential treatment options for patients after standard treatment escape. The French Sarcoma Group - Bone Tumor Study Group (GSF-GETO) created a national registry to evaluate the outcome of patients treated with off-label TTs.

Methods: Every consecutive sarcoma-patient receiving an off-label TT outside a clinical trial was included. The objective was to describe this patient efficacy and safety data in routine practice.

Results: From October 2008 to October 2011, 249 patients in 24 centers received 278 treatment lines with TTs. Twenty-five histological subtypes were included: most frequent were leiomyosarcoma (n=48, receiving sorafenib in 63%, and sunitinib in 27%), GIST (n=39, receiving sorafenib in 79%), and angiosarcoma (n=18, receiving sorafenib in 78%). The overall response rate to TTs was 15% (95% CI [10,6-20,2]), the disease control rate at 2 months was 59%. The median progression-free survival was 4,1 months (IC 95% [3,2-4,8]). Three complete responses were observed. No toxic death occurred, grade 3 and 4 toxicities were reported in 74 (27%) and 14 patients (5%) respectively.

Conclusion: Off-label TTs can be used for sarcoma patients in routine practice with an acceptable toxicity profile and efficacy similar to that reported in non-randomized clinical trials.

Show MeSH
Related in: MedlinePlus