No abstract

e15743 Background: NG is a standard 1st line treatment for APC. Although recommended in 2nd line after FOLFIRINOX, there is little evidence of its efficacy, tolerability and of markers of efficacy. Methods: We performed a multicenter retrospective cohort study, including patients (pts) with APC from 5 centers in Portugal treated with 2nd line NG after 1st line FOLFIRINOX from 01/2013-12/2016. We collected demographic, clinicopathological characteristics and treatment data. We used descriptive statistics, Kaplan-Meier methods and Cox proportional hazards analysis. Results: 30 pts were included; median age was 64 years (range 45–78); the majority had stage IV (90%) disease, an ECOG Performance Status of 0 (76.7%) and had received a median of 8.5 cycles of FOLFIRINOX (range 1–18). A median of 6 cycles of NG were administered (range 1–13). Median progression free survival (PFS) and overall survival (OS) were 6.4 months (CI 95% 3.0-8.5) and 11.4 months (CI 95% 8.4–16.5), respectively, and did not differ by age < 65 or ≥65 (p = 0.87; p = 0.57 respectively). The most frequent toxicity was fatigue (66.6%, any grade). Grade 3-4 events occurred in 40% of pts – thrombocytopenia in 16.7%, neutropenia in 10.0%; anemia, sensorial neuropathy, fatigue and diarrhea each occurred in 3.3% of patients. No febrile neutropenia events or toxic deaths occurred. Median CA 19.9 at the beginning of NG was 1254U/mL (IQR: 207–6775); the median decrease of CA19.9 at 3 months was 45U/mL (IQR:-1373– +174). CA 19.9 variation at 3 months did not correlate with PFS (p = 0.53) or OS (p = 0.09) in multivariate analysis (adjusted for age and stage at diagnosis). Neutrophil to Lymphocyte ratio (NLR) was high ( > 3.0) in 37.5% of patients before 1st line treatment and in 27.6% at the beginning of NG. In multivariate analysis NLR before 1st or 2nd chemotherapy lines were not associated with PFS (p = 0.39; p = 0.14 respectively) or OS (p = 0.44; p = 0.12, respectively). Conclusions: In this cohort of pts with APC, NG was an effective and well tolerated 2nd line regimen after FOLFIRINOX failure, even in pts ≥65 years. Neither CA19.9 variation at 3 months nor NLR were markers of NG clinical benefit.

The prognosis in the setting of metastatic castration-resistant prostate cancer patients (mCRPC) remains limited. Therefore, novel treatment strategies remain an unmet need. Antibody-drug conjugates (ADC) emerged as a new drug concept with the potential to deliver a cytotoxic payload with limited off-target toxicity and potentially bystander effect. Following the success of ADCs in breast cancer and urothelial tumours, their activity in prostate cancer is now under investigation. Thus, the aim of this systematic review was to identify published and ongoing prospective clinical trials regarding ADC treatment in prostate cancer.A systematic search of PubMed, MEDLINE, and Web of Science was conducted as per PRISMA guidelines to identify prospective clinical trials of ADC in prostate cancer. Trials are currently ongoing on ClinicalTrials.gov and in the EU. The Clinical Trials Register was also identified. Abstracts, publications in languages other than English, review articles, retrospective analyses, and phase I trials were excluded.A total of six phase I/II prospective clinical trials already published were included. Seven ongoing trials were also identified. All studies were in the refractory/advanced tumour setting, and two included only mCRPC patients. The ADC targets were prostate-specific membrane antigen (PSMA), trophoblast cell surface antigen-2 (TROP-2), six-transmembrane epithelial antigen of prostate-1 (STEAP-1), tissue factor (TF), deltalike protein 3 (DLL-3), B7-H3 family of proteins (B7-H3), and human epidermal growth factor receptor 2 (HER2). Regarding the efficacy of PSMA ADC treatment in the second-line or beyond mCRPC setting, a PSA ≥ 50% decline rate in 14% of all treated patients was reported. One patient achieved a complete response with TROP-2 ADC. Overall, a wide range of safety issues were raised, particularly in connection with neuropathy and hematologic toxicity.Novel therapies have been changing the scope of treatment in mCRPC. ADCs seem to provide efficacy benefits, even with potential toxicity. The results of most prospective ongoing studies are still awaited, and a longer follow-up time is warranted to evaluate the real impact of ADCs in PCa.