Medical Oncology Department, Hospital 12 de Octubre, Madrid, Spain
Jose A. Lopez-Martin , Ana M. Arance , Luis De La Cruz-Merino , Ana Illescas , Izazkun Valduvieco , Alfonso Berrocal , José López Torrecilla , Ivan Marquez Rodas , Maria Teresa Curiel Garcia , Virtudes Soriano , Ana Alvarez , M.L. Chust Vicente , Delvys Rodriguez-Abreu , M.C. Peñas Sanchez , Eva Muñoz-Couselo , Javier Aristu , Antonio Gomez Caamaño , Salvador Martin-Algarra
Background: Laboratory and clinical experiences suggest that radiotherapy may be synergistic with anti-CTLA-4 strategies. This hypothesis is explored in melanoma patients (pts) with brain metastases (BM) not candidate to surgery/radiosurgery. Methods: Single arm phase-2 trial evaluating Ipilimumab (IPI) and whole brain RT (WBRT), in pts with melanoma and unresectable BM. Endpoints: Primary: 1-year overall survival (OS@1y). Secondaries: progression free survival (PFS), objective response rate (ORR) and safety. Main eligibility criteria: first-BM episode, non-suitable for radical therapy; Barthel Index > 10; RTOG-RPA class-2; measurable disease; Karnofsky > 70%; LDH < 2 xULN; no rapid clinical deterioration; dexamethasone < 16 mg/d. Treatment: IPI 3mg/Kg q3weeks (4 cycles); WBRT 30Gy in 10 fractions (or equivalent). Evaluable pts: Safety > 1 IPI dose. Efficacy: complete WBRT and > 1 IPI dose. Trial required 56 evaluable pts to detect an 35% OS@1y, assuming the historical 20% OS in this population (α:0.05, β:0.8; 1-stage Fleming design). Results: From April/2014 to January/2017, 58 pts were included; 51 completed WBRT and > 1 IPI dose. Demographic characteristics: Age (median/range) 63 (37/85). Male/Female 36/22. Karnofsky (100/90; 80/70) 42. 16. BM (1, > 1, nonspecified) 14; 43; 1. Barthel Index ( > 15; 10-15) 56; 2. Steroids at baseline 31 (53,4%). Prior treatments (1, > 1) 20 (34,5%), 9 (15,5%). Previous BRAF/MEKinhibitors 18 (31%). Liver metastases 16 (27,6%). Treatment intensity: WBRT: completed in 55 pts (3 early termination). IPI 4/3/2/1 doses: 31/10/10/7 pts. Efficacy: OS@1y: 31.8% (95%CI 18.8-44.8%). 15 pts are alive > 1 year. Median PFS: 4.8mo (95%CI 2.2-3.4). Median OS 5.8mo (95%CI 3.6-5.9). Safety: Serious AEs: 40 pts (69%). Treatment-related SAEs: 11 pts (19%). IPI-related: ALT/AST (4), diarrhea (4), intestinal perforation (1), headache (1). RT-related: headache and vomiting (1). Conclusions: Concomitant IPI+WBRT is feasible and there were no unexpected safety issues. Steroids at baseline do not impair the effect of IPI in this population. OS@1y in this trial is higher than the historical results. Clinical trial information: 2013-001132- 22.
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