04 junio 2017

PM01183 o Yondelis ... Resultados de Fase II Presentados en ASCO 17 . Pacientes Portadores de BRCA2 de la línea germinal con Cáncer de Mama metastásico (MBC) en comparación con los portadores de BRCA1

La Fase III con PM01183 esta ya en Diseño .

Resultado de imagen de pm01183 breast cancerAntitumor Activity of Yondelis ( Trabectedin ) and PM01183 ( Lurbinectedin ) in Germline BRCA2 Carriers with Metastatic Breast Cancer (MBC) as compared to BRCA1 Carriers : Analysis of two Phase II Trials.


BRCA 1/2-associated breast cancer share homologous recombination deficiency, but also have independent and potentially actionable roles. Novel drugs with innovative mechanism of action, lacking cross-resistance with other used agents are needed for BRCA 1/2 MBC. Trabectedin (TR) and its analog, lurbinectedin (L), have shown to be active in BRCA 1/2 MBC. This study was sought to determine if there was a difference in activity of these agents between BRCA1 and 2 carriers.


Safety and efficacy in MBC BRCA 1/2 were analyzed in 2 separate phase II trials of single agent TR and L.


88 patients were evaluated: 34 with TR, 54 with L. Median age: 46 and 43, respectively. Median (range) prior chemotherapy lines: TR, 4 (1-10); L, 2 (0-5). Clinical responses were seen in the 2 trials (see table) and were higher in BRCA2 than in BRCA1 (33% vs 9% with TR and 61% vs 26% with L). Main adverse event was myelosuppression (grade 3-4 neutropenia / thrombocytopenia / febrile neutropenia: TR, 62.1%/24.3%/10.8% L, 66.7%/20.4%/20.4%). Non-hematological toxicity was mostly grade 1-2: fatigue, nausea/vomiting and high transaminases (grade 3/4 TR, 40.5%, L 18.5%).


Remarkable activity of trabectedin and lurbinectedin as single agents was observed in BRCA 2 associated MBC. This finding warrants further investigation. One potential mechanistic rationale is the role of both lurbinectedin and BRCA 2 in transcription. Safety was acceptable and manageable in both studies.

esponseTrabectedin 1.3 mg/m² D1 q3wks

Lurbinectedin 7 mg FD / 3.5 mg/m²
D1 q3wks

BRCA1 (n=22)
n (%)
BRCA2 (n=12)
n (%)
BRCA1 (n=31)
n (%)
BRCA2 (n=23)
n (%)
CR--2 (6.5)-
PR2 (9.1)4 (33)6 (19.4)14 (60.9)
PRnc2 (9.1)_3 (9.7)1 (4.3)
SD9 (40.9)4 (33)12 (38.7)7 (30.4)
PD9 (40.9)4 (33)8 (25.8)1 (4.3)
DOR (mo)1.62.710.26.4
PFS (mo)
OS (mo)NANA15.026.6

CR complete response; DCR disease control rate; DOR duration of response; FD flat dose; mo, months; ORR overall response rate; PD progressive disease; PFS progression-free survival; PR partial response, PRnc non-confirmed PR; SD stable disease; NA not available.