Abstract 638P
Background
MM are rare in mCRPC, with dural metastases (mts) being the most commonly reported. MM impact quality of life and are likely to be occur more often with the increasing survival of patients (pts) who benefit from more life-prolonging agents. Here, we evaluated MM in mCRPC pts.
Methods
The records of mCRPC pts screened between March 2017 and October 2019 in clinical trials of PARP inhibitors at Gustave Roussy were evaluated for the diagnosis (dg) of MM. Patients lost to follow-up (FU) were excluded. Dg of MM was based on typical clinical and imaging findings, after radiological review. We assessed the incidence of MM, the time from CRPC to MM dg, MM’s presentation, progression-free survival (PFS) and overall survival (OS).
Results
Out of 201 pts, 23 (11.4%) developed MM (all dural mts and 3 had also leptomeningeal mts). Characteristics of pts with and without MM are depicted in Table. At MM dg, pts had a median PSA of 515 ng/mL (127-1242), an ECOG performance status ≥2 in 18/23 (78%), neurologic symptoms in 21/23 (91%) and systemic progression in 21/23 (91%). Pts had nodular MM in 14/28 (61%), with a median diameter of 15 mm (13-40). Intracranial bleeding was detected in 5 pts. Active treatment was given in 9 pts (ECOG<4): 6 chemotherapy, 3 radiotherapy. Clinical response occurred with chemotherapy alone in 3 pts (2 carboplatin, 1 docetaxel) and with steroids in 8/14 pts. The median PFS with active treatment was 3.6 months (95%CI 1-6.3). The median OS since MM dg was 5.29 months (95%CI: 1.76-8.81) and 2.07 months (95%CI: 1.98-2.15) in pts with and without active treatment, respectively (log rank, p=0.012). Death occurred with concomitant extracranial progression. Table: 638P
| No MM (n=178) | MM (n=23) | P value | |
| Time from CRPC to MM dg or last date of FU, months (95%CI) | 33.18 (27.09-39.27) | 28.9 (23.7-34) | 0.01 |
| Skull mts | 34/123 (28%) | 14/20 (70%) | 0.0005 |
| Lines of therapy in the mts phase, median [range] | 4 [3-5] | 4 [3-5] | |
| DNA damage repair defects (DDR+) in tissue | 36/95 (38%) | 5/10 (50%) | 0.5 |
| DDR+ liquid biopsy* | 53/83 (64%) | 11/13 (85%) | 0.2 |
*monoallelic defects included.
Conclusions
MM occur in advanced, heavily pre-treated mCRPC, who usually have skull mts. Pts can present large nodular lesions and intracranial bleeding. Neurological deterioration is common and treatment can partially relief symptoms.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Karim Fizazi.
Funding
Has not received any funding.
Disclosure
E. Colomba-Blameble: Honoraria (self): IPSEN, BMS, Pfizer, Sanofi, GSK; Honoraria (institution): IPSEN; Advisory/Consultancy: IPSEN, BMS, Pfizer, Sanofi, GSK; Travel/Accommodation/Expenses: IPSEN, BMS, Pfizer, Novartis. P. Lavaud: Travel/Accommodation/Expenses: Astellas Oncology; Ipsen; Janssen; Mundipharma Research. C. Massard: Advisory/Consultancy: Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion; Leadership role, Investigator/Sub-investigator of Clinical Trials: Abbvie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveopharmaceuticals, Bayer, Beigene, Blueprint, BMS, BoeringerIngelheim, Celgene, Chugai, Clovis, DaiichiSankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 biomed. Y. Loriot: Honoraria (self): Pfizer; Sanofi; Advisory/Consultancy: Astellas Pharma; AstraZeneca; Bristol-Myers Squibb; Clovis Oncology; Janssen; Janssen (Inst); MSD Oncology; MSD Oncology (Inst); Roche; Seattle Genetics; Research Funding - AstraZeneca (Inst); Boehringer Ingelheim (Inst); Clovis Oncology (Inst); CureVac (; Travel/Accommodation/Expenses: Astellas Pharma; AstraZeneca; Janssen Oncology; MSD Oncology; Roche; Seattle Genetics. L. Albiges: Advisory/Consultancy: Amgen (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); Bristol-Myers Squibb (Inst); Corvus Pharmaceuticals (Inst); Exelixis (Inst); Ipsen (Inst); Merck (Inst); MSD (Inst); Novartis (Inst); Novartis (Inst); Peloton therapeutics (Inst); Pfizer (Inst); Ro; Research grant/Funding (institution): Bristol-Myers Squibb ; Travel/Accommodation/Expenses: BMS; MSD. G. Baciarello: Honoraria (self): Janssen, Roche; Advisory/Consultancy: Amgen, Astellas Oncology, Janssen, Roche; Travel/Accommodation/Expenses: Astellas Oncology, Ipsen, Janssen, Roche. K. Fizazi: Honoraria (self): Astellas Pharma, Bayer, Janssen, Sanofi; Advisory/Consultancy: Amgen (Inst), Astellas Pharma, AstraZeneca (Inst), Bayer, Curevac (Inst), ESSA (Inst), Janssen Oncology, Orion Pharma GmbH, Sanofi; Travel/Accommodation/Expenses: Amgen, Janssen. All other authors have declared no conflicts of interest.