Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Results of a Prospective Phase II Study

Optimal therapy of biochemically relapsed prostate cancer (BRPC) after local treatment is elusive. An established modified citrus pectin (PectaSol®, P-MCP), a dietary polysaccharide, is an established antagonist of galectin-3, a carbohydrate-binding protein involved in cancer pathogenesis. Based on PSA dynamics, we report on the safety and the primary outcome analysis of a prospective phase II study of P-MCP in non-metastatic BRPC based. Sixty patients were enrolled, and one patient withdrew after a month. Patients (n = 59) were given P-MCP, 4.8 grams X 3/day, for six months. The primary endpoint was the rate without PSA progression and improved PSA doubling time (PSADT). Secondary endpoints were the rate without radiologic progression and toxicity. Patients that did not progress by PSA and radiologically at six months continued for an additional twelve months. After six months, 78% (n = 46) responded to therapy, with a decreased/stable PSA in 58% (n = 34), or improvement of PSADT in 75% (n = 44), and with negative scans, and entered the second twelve months treatment phase. Median PSADT improved significantly (p = 0.003). Disease progression during the first 6 months was noted in only 22% (n = 13), with PSA progression in 17% (n = 10), and PSA and radiologic progression in 5% (n = 3). No patients developed grade 3 or 4 toxicity.

Prostate Cancer Metastasis to the Pituitary Gland Manifesting as Corticosteroid Withdrawal, and the Impact of the Switch from Prednisone to Dexamethasone on Survival Time

Despite improvements in the diagnosis and treatment of cancers, the incidence of pituitary metastasis has increased. Prostate cancer metastasis to the pituitary, however, is rare, and these tumors usually grow rapidly. They are also more likely to be located in the posterior pituitary, and the presenting symptoms are often nonspecific, which makes early diagnosis challenging. The management of this condition is usually multidisciplinary, and requires careful assessment and decision making. We present a case of a patient who developed prostate cancer metastasis to the pituitary. In this report, we show that patients with prostate cancer on corticosteroid therapy who develop withdrawal symptoms or other endocrine symptoms should be assessed for pituitary and other brain metastasis. This case report also discusses the impact of switching from prednisone and abiraterone to dexamethasone and abiraterone. Our report shows that patients on abiraterone and prednisone whose PSA has increased, but who have no radiologic progression, may have their PSA controlled and thereby improved survival time when they are switched to abiraterone and dexamethasone.

Sorafenib for Desmoid Tumors. A Cost Analysis: Too Much for Too Little?

Background: A recent randomized trial showed that sorafenib increased progression free survival (PFS) in patients with desmoid tumors despite many patients experiencing stable disease or spontaneous regression without treatment. Using these trial data, we completed a cost analysis of sorafenib efficacy through two years of treatment. Methods: 2019 Medicare Part D rates for sorafenib were used (dose 400 mg/day, cost $309/day). Yearly costs per progression and objective response were calculated. Radiologic progression and response were defined using Response Evaluation Criteria in Solid Tumors (RECIST). Patients with disease progression were separately analyzed in two groups: both clinical and radiologic (CAR), and radiologic alone. Results: 84 previously randomized patients were analyzed (placebo: 35, sorafenib: 49). After 1 year, sorafenib was associated with 43% absolute risk reduction (ARR) of CAR progression and number-needed-to-treat (NNT) of 2.3 patients/year, costing $259,406. After 2 years, ARR was 48% and NNT of 2.1 patients/year, costing $473,697. When assessing only patients with RECIST defined radiologic progression, sorafenib patients had ARR of 13.9% with NNT 7.2 and estimated costs of $812,052 at one year. Two-year ARR was 17.5% with NNT 5.7 and estimated costs $1,285,052. Sorafenib patients experienced improved RECIST partial response rates at 1 and 2 years of 14.7% and 14.3%, with NNT 6.8 and 6.9, and costs of $766,938 and $1,556,433; respectively. Conclusion: For the treatment of desmoid tumors, Sorafenib led to improved PFS, but at a substantial cost per patient. Beneficial RECIST outcomes were less likely and at higher cost. Patients should be informed of possible benefits of treatment versus potential financial burden.

Rising Circulating Tumor DNA As a Molecular Biomarker of Early Disease Progression in Metastatic Breast Cancer

PURPOSE Accurate monitoring of therapeutic response remains an important unmet need for patients with metastatic breast cancer (MBC). Analysis of tumor genomics obtained via circulating tumor DNA (ctDNA) can provide a comprehensive overview of tumor evolution. Here, we evaluated ctDNA change as an early prognostic biomarker of subsequent radiologic progression and survival in MBC. PATIENTS AND METHODS Paired blood samples from patients with MBC were analyzed for levels of ctDNA, carcinoembryonic antigen, and cancer antigen 15-3 at baseline and during treatment. A Clinical Laboratory Improvement Amendments–certified sequencing panel of 73 genes was used to quantify tumor-specific point mutations in ctDNA. Multivariable logistic regression analysis was conducted to evaluate the association between ctDNA rise from baseline to during-treatment (genomic progression) and subsequent radiologic progression and progression-free survival (PFS). RESULTS Somatic mutations were detected in 76 baseline samples (90.5%) and 71 during-treatment samples (84.5%). Patients with genomic progression were more than twice as likely to have subsequent radiologic progression (odds ratio, 2.04; 95% CI, 1.74 to 2.41; P < .0001), with a mean lead time of 5.8 weeks. Genomic assessment provided a high positive predictive value of 81.8% and a negative predictive value of 89.7%. The subset of patients with genomic progression also had shorter PFS (median, 4.2 v 8.3 months; hazard ratio, 2.97; 95% CI, 1.75 to 5.04; log-rank P < .0001) compared with those without genomic progression. CONCLUSION Genomic progression, as assessed by early rise in ctDNA, is an independent biomarker of disease progression before overt radiologic or clinical progression becomes evident in patients with MBC.

Combination therapy in rheumatoid arthritis

The therapeutic armamentarium available for treatment of rheumatoid arthritis (RA) has changed significantly over the past 30 years, transforming the therapeutic landscape and prognosis for a substantial proportion of patients with RA. Combination therapies represent an important therapeutic paradigm for management of rheumatoid arthritis. The rationale for combination therapies is clear and demonstrated to bring treatment benefit to patients achieving lower disease activity scores and reduced radiologic progression according to ‘treat-to-target’ principles. A rigorous evidence-based debate is required involving not only parameters related to disease activity scores and radiologic progression, but related to the cost-effectiveness analysis of using many of these newer agents compared to older csDMARDs. This chapter addresses the evidence related to the utilization of combination strategies for the management of RA as compared to monotherapy.

AB0305 STUDY OF CORRELATION OF B-CELL LEVEL AND PROGRESSION OF BONE DESTRUCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING RITUXIMAB THERAPY

Background:Rheumatoid arthritis is a chronic autoimmune disease characterised by inflammation of the synovial tissue and destruction of the underlying cartilage and bone. The goal of antirheumatic treatment is not only to attenuate the clinical symptoms of joint inflammation, but also to inhibit the progression of joint destruction. Rituximab - it is a chimeric monoclonal antibody that targets the CD20 molecule expressed on the surface of B cells. It has been successfully used to treat rheumatoid arthritis, and it is worth noting that his antidestructive effect sometimes does not meet the clinical.Objectives:The aim of our study was to evaluate the correlation between the degree of В-cell depletion and the development of the clinical and antidestructive effects of Rituximab (RTM) therapy in patients with rheumatoid arthritis (RA).Methods:the study included 108 patients (pts) with rheumatoid arthritis, most are middle-aged women with high disease activity (mean DAS28 6,1±1.04, RF-positive 77%, ACCP-positive 83%) treated with RTX (1000 mgx2 or 500 mgx2). Clinical effect was scored by EULAR criteria, radiographic progression was assessed using Sharp/van der Heijde (SvH) modified scoring method. B-cell level was measured with flow cytometry.Results:patients who were treated by different doses of RTX (500 x2 or 1000 x2) had good response. After 48 week of treatment RTX clinical improvement was achieved in 65% pts, good and moderate response by EULAR criteria in 23 % and 42 % pts respectively. Noteworthy, after 12 months of treatment RTX radiological progression was absent in 50 % pts with high disease activity. There was no significant difference in the degree of B-cell reduction when assessing the antidestructive effect. However, in assessing the clinical effect, it was noted that depletion of B cells in patients with RA in a state of remission (median 0.05% B cells) was more pronounced than in patients with signs of disease activity (2.03% B cells).Conclusion:rituximab therapy slows the radiologic progression regardless of the therapeutic effect. Radiologic progression did not show any dependence on the degree of B-cell reduction. The most pronounced depletion of B cells was observed in RA patients in a state of remission.Disclosure of Interests:Anastasia Kudryavtseva: None declared, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Alexander Smirnov: None declared, Svetlana Glukhova: None declared, Eugenia Aronova: None declared, Galina Gridneva: None declared

Association of body composition with survival and efficacy of first-line treatment in patients with castration-resistant prostate cancer.

115 Background: We aimed to investigate the association of body composition with survival and efficacy of first-line treatments in patients with castration-resistant prostate cancer (CRPC). Methods: Records of CRPC patients who were treated with first-line docetaxel or androgen receptor signaling inhibitors (ARSi) between 2005 and 2018 were reviewed. Skeletal muscle index (SMI), visceral fat index, and subcutaneous fat index were evaluated using pretreatment computed tomography images. Results: Of the 230 eligible patients, 144 patients received docetaxel and 86 received ARSi as the first-line treatment for CRPC. SMIhi (based on median value) group had higher prostate-specific antigen (PSA) progression-free survival (median 13.5 vs. 8.3 months, p=0.030), radiologic progression-free survival (14.9 vs. 9.1 months; p<0.001), and overall survival (24.1 vs. 16.9 months, p=0.015) compared than SMIlo group. In multivariable analysis, SMI was independently associated with risk of PSA progression (HR=0.68; 95% CI, 0.50-0.93; p=0.017), radiologic progression (HR=0.54; 95% CI, 0.39-0.75; p=0.001), and overall survival (HR=0.72; 95% CI, 0.52-0.98; p=0.037), regardless of BMI. In docetaxel-treated patients, PSA progression-free survival (13.5 vs. 5.9 months, p=0.016) and radiologic progression-free survival (14.6 vs. 6.7 months, p<0.001) were higher in SMIhi than SMIlo group. However, PSA progression-free survival and radiologic progression-free survival were similar between two groups in ARSi-treated patients. Based on treatment-specific hazards of radiologic progression, patients with SMIlo are more likely to benefit from ARSi compared than docetaxel. Conclusions: High skeletal muscle mass may be associated with reduced risks of disease progression and mortality in patients with CRPC. However, the significance of these relationships is limited in patients treated with docetaxel. These results suggest that skeletal muscle mass may be helpful in treatment selection and predicting treatment response in CRPC. Further prospective studies are warranted.