Patterns of care, prognosis, and survival of patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib.

Italiano, Antoîne; Cioffi, A.; Maki, Robert G.; Schöffski, Patrick; Rutkowski, Piotr; Cesne, A. Le; Duffaud, F.; Adenis, Antoine; Isambert, Nicolás; Bompas, Emmanuelle; Blay, J-Y.; Casali, Paolo G.; Coco, Paola; D’Adamo, David R.; Keohan, Mary Louise; Toulmonde, Maud; Antonescu, Cristina; Dębiec‐Rychter, Maria; Coindre, J.M.; Nguyen, Binh Bui

doi:10.1200/jco.2011.29.15_suppl.10044

Cited by 6 publications

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“…Nonetheless, these results agree with recent findings obtained with imatinib, suggesting that continued TKI treatment or TKI rechallenge in patients with GIST is beneficial. 13,14 In the current study, dosing interruptions and/or reductions were implemented in a relatively high proportion of patients (53% and 43%, respectively). This active management of sunitinib dosing allowed prolonged treatment in many patients (median treatment duration, 7.0 months, with >30% of patients treated for >1 year) and resulted in a relatively low proportion of patients dis-continuing treatment because of an AE (15%) compared with those who stopped treatment because of lack of efficacy (64%).…”

Section: Discussionmentioning

confidence: 94%

Clinical outcomes of patients with advanced gastrointestinal stromal tumors: Safety and efficacy in a worldwide treatment‐use trial of sunitinib

Reichardt

Kang

Rutkowski

et al. 2015

Cancer

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BACKGROUND To provide sunitinib to patients with gastrointestinal stromal tumor (GIST) who were otherwise unable to obtain sunitinib; to obtain broad safety and efficacy data from a large population of patients with advanced GIST after imatinib failure. METHODS Imatinib-resistant/intolerant patients with advanced GIST received sunitinib on an initial dosing schedule (IDS) of 50 mg/day in 6-week cycles (4 weeks on treatment, 2 weeks off). Tumor assessment frequency was per local practice, with response assessed by investigators per Response Evaluation Criteria in Solid Tumors version 1.0. Overall survival (OS) and safety were assessed regularly. Post-hoc analyses evaluated different patterns of treatment management. RESULTS At final data cutoff, 1124 patients comprised the intent-to-treat population; 15% had a baseline Eastern Cooperative Oncology Group performance status ≥2. Median treatment duration was 7.0 months. Median time to tumor progression was 8.3 months (95% confidence interval [CI], 8.0–9.4), and median OS was 16.6 months (95% CI, 14.9–18.0) with 36% of patients alive at the time of analysis. Patients in whom the IDS was modified exhibited longer median OS (23.5 months) than those treated strictly per the IDS (11.1 months). The most common treatment-related grade 3/4 adverse events (AEs) were hand-foot syndrome (11%), fatigue (9%), neutropenia (8%), hypertension (7%), and thrombocytopenia (6%). Treatment-related AEs associated with cardiac function (eg, congestive heart failure and myocardial infarction) were reported at frequencies of ≤1% each. CONCLUSIONS This treatment-use study confirms the long-term safety and efficacy of sunitinib in a large international population of patients with advanced GIST after imatinib failure.

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Section: Discussionmentioning

confidence: 94%

Clinical outcomes of patients with advanced gastrointestinal stromal tumors: Safety and efficacy in a worldwide treatment‐use trial of sunitinib

Reichardt

Kang

Rutkowski

et al. 2015

Cancer

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“…expression, as suggested by preliminary data from the SARC 09 trial investigating dasatinib in the third-line or fourth-line setting. 34 Finally, additional drugs and treatment lines might prolong survival simply because any TKI treatment is better than best supportive care, 35 and TKIs that have not been used in prior treatment lines could be of particular interest here. On the basis of our data in a limited number of patients, we conclude that dasatinib might be used in specific mutations and as an additional line of treatment to increase OS rather than as first-line treatment in patients with GIST.…”

Section: Discussionmentioning

confidence: 99%

Long‐term outcome of dasatinib first‐line treatment in gastrointestinal stromal tumor: A multicenter, 2‐stage phase 2 trial (Swiss Group for Clinical Cancer Research 56/07)

Montemurro

Cioffi

Dômont

et al. 2018

Cancer

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“…In vitro se demostró actividad para inhibir células de GIST resistentes a imatinib y sunitinb 35 , lo que conllevó a evaluar su eficacia en pacientes politratados, hallando una respuesta parcial y enfermedad estable en el 14% y 64%, respectivamente 32 . Una actualización de este estudio mostró una mediana de SLP de 5.2 meses (IC 95% 3.4-7.4 meses) y una SG de 11.6 meses (IC 95% 8.8-14.3) 33 , desenlaces respaldados por otra serie de corte transversal 36 . El caso aquí reportado tuvo un efecto terapéutico extrapolable a lo encontrado en modelos murinos que tienen resistencia primaria al imatinib mediada por la mutación V600E del BRAF.…”

Section: Discussionunclassified

Genotipo complejo en un paciente con GIST.

Becerra

Cardona

Acevedo

et al. 2012

Rev.Col.Hematol.Oncol

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Se presenta el caso de un hombre de 35 años diagnosticado de un tumor del estroma gastrointestinal (GIST) localizado en el yeyuno proximal y estratificado como de alto riesgo, en quien se resecó el primario sin evidencia de recaída, hasta documentar múltiples lesiones hepáticas, por lo que inició imatinib (Glivec®) 400 mg/día. Después de encontrar progresión, se aumentaron las dosis del inhibidor sin respuesta, por lo que inició sunitinib (Sutent®) 50 mg/día con el mismo resultado. Posteriormente, se realizó una reevaluación del histotipo y genotipificación, encontrando positividad para la mutación del exón 9 del gen KIT. A partir de noviembre del 2009, se administró sorafenib (Nexavar®) 400 mg cada 12 horas, logrando una respuesta metabólica superior al 50% (evaluada por tomografía por emisión de positrones –PET/TAC–) y parcial siguiendo los criterios descritos por Choi y colaboradores. Durante el tratamiento de tercera línea, se efectuó una nueva biopsia del tumor, que demostró un genotipo complejo, incluyendo la mutación V600E del BRAF, y manteniendo el beneficio clínico con la intervención descrita hasta julio del 2011; en el momento, el paciente continúa vivo. A continuación, se plantea un análisis de los mecanismos moleculares que explican la resistencia a los inhibidores de tirosina-quinasa y las implicaciones sobre la terapéutica del GIST.

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Patterns of care, prognosis, and survival of patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib.

Cited by 6 publications

References 0 publications

Clinical outcomes of patients with advanced gastrointestinal stromal tumors: Safety and efficacy in a worldwide treatment‐use trial of sunitinib

Clinical outcomes of patients with advanced gastrointestinal stromal tumors: Safety and efficacy in a worldwide treatment‐use trial of sunitinib

Long‐term outcome of dasatinib first‐line treatment in gastrointestinal stromal tumor: A multicenter, 2‐stage phase 2 trial (Swiss Group for Clinical Cancer Research 56/07)

Genotipo complejo en un paciente con GIST.

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