S Delaloge1, R Wolp-Diniz2, T Byrski3, J L Blum4, A Gonçalves5, M Campone6, P Lardelli7, C Kahatt7, A Nieto7, M Cullell-Young7, J Lubinski3. 1. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France suzette.delaloge@gustaveroussy.fr. 2. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. 3. Department of Medical Oncology, International Hereditary Cancer Center, Sczeczin, Poland. 4. Department of Oncology, Baylor-Charles A. Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, USA. 5. Department of Medical Oncology, Institut Paoli Calmettes, Marseille. 6. Department of Medical Oncology, Institut de Cancérologie de l'OUEST, Nantes, France. 7. Clinical R&D, PharmaMar, Colmenar Viejo, Madrid, Spain.
Abstract
BACKGROUND: Breast cancer is a heterogeneous disease defined by both germline and somatic abnormalities. In preclinical models, tumors carrying homologous recombination defects are highly sensitive to trabectedin. This phase II trial evaluated the efficacy and safety of trabectedin in BRCA1/2 germline mutation carriers with pretreated metastatic breast cancer (MBC). PATIENTS AND METHODS: Trabectedin 1.3 mg/m(2) as a 3-h i.v. infusion was administered every 3 weeks until progression or intolerance. The primary efficacy end point was the objective response rate (ORR) as per RECIST. Secondary efficacy end points comprised time-to-event end points, and changes in tumor volume and expression of tumor marker CA15.3. Safety was evaluated using the NCI-CTCAE. RESULTS: Forty BRCA1/2 germline mutation carriers with MBC were included. Confirmed partial response (PR) occurred in 6 of 35 assessable patients [ORR = 17%; 95% confidence interval (CI) 7% to 34%] and lasted 1.4-6.8 months. Median PFS was 3.9 months (95% CI 1.6-5.5 months). Eight patients (21%) showed changes in tumor volume, and 14 (40%) a clinical benefit. Trabectedin-related adverse events were generally mild/moderate, the most common being fatigue, nausea, constipation and anorexia. Severe laboratory abnormalities (neutropenia, transaminase increases) were mostly transient and noncumulative, and were managed by dose adjustments. CONCLUSIONS: With the caveat of the limited patient number, trabectedin monotherapy showed activity and was well tolerated in heavily pretreated MBC patients selected for germline BRCA mutation. These results prompt further evaluation of trabectedin alone or combined with other specific drugs in this indication. CLINICALTRIALSGOV: NCT00580112.
BACKGROUND: Breast cancer is a heterogeneous disease defined by both germline and somatic abnormalities. In preclinical models, tumors carrying homologous recombination defects are highly sensitive to trabectedin. This phase II trial evaluated the efficacy and safety of trabectedin in BRCA1/2 germline mutation carriers with pretreated metastatic breast cancer (MBC). PATIENTS AND METHODS: Trabectedin 1.3 mg/m(2) as a 3-h i.v. infusion was administered every 3 weeks until progression or intolerance. The primary efficacy end point was the objective response rate (ORR) as per RECIST. Secondary efficacy end points comprised time-to-event end points, and changes in tumor volume and expression of tumor marker CA15.3. Safety was evaluated using the NCI-CTCAE. RESULTS: Forty BRCA1/2 germline mutation carriers with MBC were included. Confirmed partial response (PR) occurred in 6 of 35 assessable patients [ORR = 17%; 95% confidence interval (CI) 7% to 34%] and lasted 1.4-6.8 months. Median PFS was 3.9 months (95% CI 1.6-5.5 months). Eight patients (21%) showed changes in tumor volume, and 14 (40%) a clinical benefit. Trabectedin-related adverse events were generally mild/moderate, the most common being fatigue, nausea, constipation and anorexia. Severe laboratory abnormalities (neutropenia, transaminase increases) were mostly transient and noncumulative, and were managed by dose adjustments. CONCLUSIONS: With the caveat of the limited patient number, trabectedin monotherapy showed activity and was well tolerated in heavily pretreated MBC patients selected for germline BRCA mutation. These results prompt further evaluation of trabectedin alone or combined with other specific drugs in this indication. CLINICALTRIALSGOV: NCT00580112.
Authors: L Boudin; A Gonçalves; R Sabatier; J Moretta; P Sfumato; P Asseeva; D Livon; F Bertucci; J-M Extra; C Tarpin; G Houvenaeghel; E Lambaudie; A Tallet; M Resbeut; H Sobol; E Charafe-Jauffret; B Calmels; C Lemarie; J-M Boher; P Viens; F Eisinger; C Chabannon Journal: Bone Marrow Transplant Date: 2016-04-04 Impact factor: 5.483
Authors: Cristina Cruz; Alba Llop-Guevara; Judy E Garber; Banu K Arun; José A Pérez Fidalgo; Ana Lluch; Melinda L Telli; Cristian Fernández; Carmen Kahatt; Carlos M Galmarini; Arturo Soto-Matos; Vicente Alfaro; Aitor Pérez de la Haza; Susan M Domchek; Silvia Antolin; Linda Vahdat; Nadine M Tung; Rafael Lopez; Joaquín Arribas; Ana Vivancos; José Baselga; Violeta Serra; Judith Balmaña; Steven J Isakoff Journal: J Clin Oncol Date: 2018-09-21 Impact factor: 44.544