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Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC.A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented.Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer.Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.

PURPOSE Two poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and rucaparib) are US Food and Drug Administration–approved for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/ 2 mutations, but the relative efficacy of PARP inhibition in BRCA1- versus BRCA2-altered mCRPC is understudied. METHODS We conducted a multicenter retrospective analysis involving 12 sites. We collected genomic and clinical data from 123 patients with BRCA1/ 2-altered mCRPC who were treated with PARP inhibitors. The primary efficacy end point was the prostate-specific antigen (PSA) response (≥ 50% PSA decline) rate. Secondary end points were PSA progression-free survival (PSA-PFS), clinical or radiographic PFS, and overall survival. We compared clinical outcomes, and other genomic characteristics, among BRCA1- versus BRCA2-altered mCRPC. RESULTS A total of 123 patients (13 BRCA1 and 110 BRCA2) were included. PARP inhibitors used were olaparib (n = 116), rucaparib (n = 3), talazoparib (n = 2), and veliparib (n = 2). At diagnosis, 72% of patients had Gleason 8-10 disease. BRCA1 patients were more likely to have metastatic disease at presentation (69% v 37%; P = .04). Age, baseline PSA, metastatic distribution, and types of previous systemic therapies were similar between groups. There were equal proportions of germline mutations (51% v 46%; P = .78) in both groups. BRCA1 patients had more monoallelic (56% v 41%; P = .49) and concurrent TP53 (55% v 36%; P = .32) mutations. PSA50 responses in BRCA1- versus BRCA2-altered patients were 23% versus 63%, respectively ( P = .01). BRCA2 patients achieved longer PSA-PFS (HR, 1.94; 95% CI, 0.92 to 4.09; P = .08), PFS (HR, 2.08; 95% CI, 0.99 to 4.40; P = .05), and overall survival (HR, 3.01; 95% CI, 1.32 to 6.83; P = .008). Biallelic (compared with monoallelic) mutations, truncating (compared with missense) mutations, and absence of a concurrent TP53 mutation were associated with PARP inhibitor sensitivity. CONCLUSION PARP inhibitor efficacy is diminished in BRCA1- versus BRCA2-altered mCRPC. This is not due to an imbalance in germline mutations but might be related to more monoallelic mutations and/or concurrent TP53 alterations in the BRCA1 group.

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.MethodsThis single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.ResultsTwenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).ConclusionsHu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.Trial registrationNCT01137071.

Prostate cancer is the second most common cancer and the fifth leading cause of cancer deaths. In Brazil, it is likewise the second most common cancer among men, second only to non-melanoma skin cancers. The aim of this consensus is to align different opinions and interpretations of the medical literature in a practical and patient-oriented approach. The first Brazilian Consensus on the Treatment of Advanced Prostate Cancer was published in 2017, with the goal of reducing the heterogeneity of therapeutic conduct in Brazilian patients with metastatic prostate cancer. We acknowledge that in Brazil the incorporation of different technologies is a big challenge, especially in the Sistema Único de Saúde (SUS), which allows for the disparity in the options available to patients treated in different institutions. In order to update the recommendations and to make them objective and easily accessible, once more a panel of specialists was formed in order to discuss and elaborate a new Brazilian Consensus on Advanced Prostate Cancer. This Consensus was written through a joint initiative of the Brazilian Society of Clinical Oncology (SBOC) and the Brazilian Society of Urology (SBU) to support the clinical decisions of physicians and other health professionals involved in the care of patients with prostate cancer.

Background First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding Merck Sharp & Dohme.

5076 Background: LACOG 0415 is a phase II, open-label, clinical trial evaluating ADT-free alternatives for advanced castration sensitive prostate cancer (CSPC). Methods: Patients with locally advanced, high-risk biochemical recurrence or metastatic CSPC were randomized (1:1:1) to receive ADT with abiraterone acetate plus prednisone (ADT+AAP), apalutamide alone (APA), or apalutamide with AAP (APA+AAP). The primary endpoint of the trial was the proportion of patients who achieved PSA≤0.2 ng/mL level at week 25. Patients without disease-progression and with clinical benefit after week 25 were allowed to maintain treatment at the discretion of physicians. Herein, we presented the outcomes of 2 year-overall survival (2y-OS) and time-to-treatment failure (TTF). The time-to-event endpoint was estimated by Kaplan-Meier method and compared by stratified log-rank test. Results: 128 patients were randomized to the ADT+AAP (n = 42), APA (n = 42), and APA+AAP (n = 44) arms. At week 25, PSA≤0.2 ng/mL was observed in 75.6% (95%CI 59.7%-87.6%), 60.0% (95%CI 43.3%-75.1%), and 79.5% (95%CI 63.5%-90.7%) of patients in the ADT+AAP, APA, and APA+AAP arms, respectively. 110 patients continued treatment after week 25. At the 2-year visit, 80 (62.5%) patients remained on the study medication. Median TTF was 24.0 months (95%CI 23.3 - 24.0) with ADT+AAP, 24.0 months (95%CI not estimated) with APA, and 24.0 months (95%CI 13.0-24.0) with APA+AAP. The main reasons for treatment discontinuation were disease progression (n = 8, 6.3%), toxicity (n = 10, 7.8%), death (n = 6, 4.7%), withdrawal (n = 4, 3.1%), and other (n = 19, 14.8%). The estimated proportion of patients who were alive at 2 years (2y-OS rate) was 92.5% (95%CI 84.3-100) with ADT+AAP, 87.9% (95%CI 77.9-97.8) with APA, and 92.7% (95%CI 84.8-100) with APA+AAP (p = 0.5926). 2y-OS was 92.9% (95% CI 85.3 - 96.2) in patients with PSA ≤ 0.2 ng/mL at week 25, while 2y-OS was 85.0% (95% CI 72.9-97.1) in patients with PSA > 0.2 ng/mL at week 25 (p = 0.1250). Conclusions: Patients with advanced CSPC treated with ADT+AAP, APA, or APA+AAP had high rates of PSA response and favorable 2y-OS. PSA ≤ 0.2 ng/mL at week 25 seems to be a surrogate prognostic predictor of OS in advanced CSPC. In the overall sample, patients with PSA ≤ 0.2 ng/mL at week 25 had higher 2y-OS rate than those with PSA > 0.2 ng/mL at week 25 (92.9% vs. 85.0%), however without statistical significance. Clinical trial information: NCT02867020.

Purpose: Ultrasound-magnetic resonance imaging (US-MRI) fusion biopsy (FB) improves the detection of clinically significant prostate cancer (PCa). We aimed to compare the Gleason upgrading (GU) rates and the concordance of the Gleason scores in the biopsy versus final pathology after surgery in patients who underwent transrectal ultrasound (TRUS) systematic random biopsies (SRB) versus US-MRI FB for PCa. Materials and Methods: A retrospective analysis of data that were collected prospectively from January 2011 to June 2016 from patients who underwent prostate biopsy and subsequent radical prostatectomy. The study cohort was divided into two groups: US-MRI FB (Group A) and TRUS SRB (Group B). US-MRI FB was performed in patients with a previous MRI with a focal lesion with a Likert score ≥3; otherwise, a TRUS SRB was performed. Results: In total, 73 men underwent US-MRI FB, and 89 underwent TRUS SRB. The GU rate was higher in Group B (31.5% vs. 16.4%; p=0.027). According to the Gleason grade pattern, GU was higher in Group B than in Group A (40.4% vs. 23.3%; p=0.020). Analyses of the Gleason grading patterns showed that Gleason scores 3+4 presented less GU in Group A (24.1% vs. 52.6%; p=0.043). The Bland-Altman plot analysis showed a higher bias in Group B than in Group A (-0.27 [-1.40 to 0.86] vs. −0.01 [-1.42 to 1.39]). In the multivariable logistic regression analysis, the only independent predictor of GU was the use of TRUS SRB (2.64 [1.11 – 6.28]; p=0.024). Conclusions: US-MRI FB appears to be related to a decrease in GU rate and an increase in concordance between biopsy and final pathology compared to TRUS SRB, suggesting that performing US-MRI FB leads to greater accuracy of diagnosis and better treatment decisions.

Background Androgen deprivation therapy (ADT) combined with apalutamide, abiraterone acetate plus prednisone, enzalutamide, or docetaxel are the standard treatments for advanced castration-sensitive prostate cancer (CSPC). We investigated ADT-free alternatives for advanced CSPC. Patients and methods LACOG 0415 is a phase 2, open-label, non-comparative, randomized trial. Patients with advanced CSPC were randomized (1:1:1) to receive goserelin plus abiraterone acetate and prednisone (ADT plus AAP arm), apalutamide (APA arm), or apalutamide plus abiraterone acetate and prednisone (APA plus AAP arm). The primary endpoint was the proportion of patients with PSA of ≤0.2 ng/mL at week 25 in the modified intention-to-treat population. Safety analyses were performed in all patients with at least one dose of the study drug. Results Of 128 randomized patients, 120 patients were evaluable for PSA response at week 25; 17.2% had a high-risk biochemical recurrence, 8.6% had locally advanced disease, and 74.2% had distant metastases. At week 25, PSA of ≤0.2 ng/mL was observed in 75.6% (95%CI 59.7%–87.6%), 60.0% (95%CI 43.3%–75.1%), and 79.5% (95%CI 63.5%–90.7%) of patients in ADT plus AAP, APA, and APA plus AAP arms, respectively. PSA decline of ≥80% was observed in 100%, 90.0%, and 97.4%, respectively. Grade 3–4 AEs were observed in 31.0%, 21.4% and 36.4%, respectively. Testosterone levels increased significantly in the APA arm and decreased significantly in ADT plus AAP and APA plus AAP arms. Conclusions ADT-free alternatives provide a high PSA response in advanced CSPC, although the APA arm did not reach the expected rate of PSA of ≤0.2 ng/mL at week 25. These results warrant further investigation of ADT-free treatments as alternatives in advanced CSPC. Source study registration ClinicalTrials.gov NCT02867020 .

Two poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and rucaparib) are US Food and Drug Administration–approved for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 mutations, but the relative efficacy of PARP inhibition in BRCA1- versus BRCA2-altered mCRPC is understudied. METHODS: We conducted a multicenter retrospective analysis involving 12 sites. We collected genomic and clinical data from 123 patients with BRCA1/2-altered mCRPC who were treated with PARP inhibitors. The primary efficacy end point was the prostate-specific antigen (PSA) response (≥ 50% PSA decline) rate. Secondary end points were PSA progression-free survival (PSA-PFS), clinical or radiographic PFS, and overall survival. We compared clinical outcomes, and other genomic characteristics, among BRCA1- versus BRCA2-altered mCRPC. RESULTS: A total of 123 patients (13 BRCA1 and 110 BRCA2) were included. PARP inhibitors used were olaparib (n = 116), rucaparib (n = 3), talazoparib (n = 2), and veliparib (n = 2). At diagnosis, 72% of patients had Gleason 8-10 disease. BRCA1 patients were more likely to have metastatic disease at presentation (69% v 37%; P = .04). Age, baseline PSA, metastatic distribution, and types of previous systemic therapies were similar between groups. There were equal proportions of germline mutations (51% v 46%; P = .78) in both groups. BRCA1 patients had more monoallelic (56% v 41%; P = .49) and concurrent TP53 (55% v 36%; P = .32) mutations. PSA(50) responses in BRCA1- versus BRCA2-altered patients were 23% versus 63%, respectively (P = .01). BRCA2 patients achieved longer PSA-PFS (HR, 1.94; 95% CI, 0.92 to 4.09; P = .08), PFS (HR, 2.08; 95% CI, 0.99 to 4.40; P = .05), and overall survival (HR, 3.01; 95% CI, 1.32 to 6.83; P = .008). Biallelic (compared with monoallelic) mutations, truncating (compared with missense) mutations, and absence of a concurrent TP53 mutation were associated with PARP inhibitor sensitivity. CONCLUSION: PARP inhibitor efficacy is diminished in BRCA1- versus BRCA2-altered mCRPC. This is not due to an imbalance in germline mutations but might be related to more monoallelic mutations and/or concurrent TP53 alterations in the BRCA1 group.

Purpose: Lewis Y antigen is expressed in 44 to 90% of breast cancer. The expression of the antigen in carcinoma tissue is different from what occurs in normal tissue. The objective of the present study was to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone receptor-positive and Lewis Y-positive breast cancer, after progression on endocrine therapy.Methods: A single-arm phase II study was conducted in 7 centers. Patients with advanced hormone receptor-positive breast cancer who had failed previous first-line endocrine therapy were included. All patients were required to present tumoral expression of Lewis Y antigen by immunohistochemistry. Treatment consisted of hu3S193 antibody at intravenous doses of 20 mg/m2 weekly given at 8-week cycles. The primary endpoint was clinical benefit rate. Results: The study stopped accrual after an unplanned interim analysis since the hu3S193 antibody lacked sufficient activity to justify the study continuation. Twenty-two patients were enrolled; 21 were included in the efficacy analysis. The clinical benefit rate was 19%, with four patients presenting stable disease confirmed after 24 weeks. One patient received the medication for more than 2 years, with prolonged stable disease. No partial or complete responses were observed. Median time to progression and overall survival were 5.4 and 37.5 months, respectively. Conclusions: The humanized anti-Lewis Y monoclonal antibody, hu3S193, showed insufficient activity in this cohort. However, we cannot rule out the possibility of activity in a more strictly selected subgroup of patients with higher levels of Lewis Y tumoral expression.Trial registration: Clinicaltrials.gov, NCT01370239. Registered 9 June 2011, https://clinicaltrials.gov/ct2/show/NCT01370239

Introduction Severe neutropenia is a dose-limiting factor that occurs in up to 82% of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. This study evaluated the effectiveness of granulocyte colony-stimulating factor (G-CSF) plus ciprofloxacin as prophylaxis in post-docetaxel patients with mCRPC treated with cabazitaxel and at high risk for neutropenia. Patients and Methods This was a phase IV, multicenter, open-label, single-arm interventional study with men aged ≥ 65 years (or 12 weeks. Cabazitaxel 25 mg/m2 and prednisone were given on day 1, every 21 days. G-CSF was administered on days 2 to 8 of each cycle or until an absolute neutrophil count > 2000/mm3, and ciprofloxacin 1000 mg was given orally on days 5 to 12. The rate of neutropenia grade ≥ 3 during the first cycle (primary endpoint), and frequency of neutropenia grade ≥ 3, febrile neutropenia, diarrhea grade ≥ 3, prostate-specific antigen response, and quality of life during treatment (secondary end points) were estimated. Results We included 46 patients. The mean number of cabazitaxel cycles was 9.5. During the first cycle, 40.0% of patients had neutropenia grade ≥ 3, and 42.2% had at least 1 episode of neutropenia during treatment. Febrile neutropenia and diarrhea grade ≥ 3 occurred in 1 patient each. Twenty-nine (64.4%) patients achieved prostate-specific antigen response, and 77.2% improved quality of life scores in at least 1 visit. Conclusions Prophylactic G-CSF was effective in preventing neutropenia grade ≥ 3 and other hematologic complications during treatment with cabazitaxel 25 mg/m2 in post-docetaxel patients with mCRPC at high risk for neutropenia. The role of prophyclatic ciprofloxacin to prevent febrile neutropenia in this setting is still unclear and needs to be further evaluated.

The biochemical recurrence after local treatment for prostate cancer is an often challenging condition of clinical management. The aim of this report is to demonstrate the importance of the association of various imaging methods in the identification and subsequent accurate percutaneous biopsy in patients with recurrence of prostate cancer, especially in unusual sites. An 86 years old male with biochemical recurrence, during radiological investigation a PET-MRI was noted the presence of an asymmetry of the vas deferens with PSMA-68Ga uptaken, suggesting the recurrence. A percutaneous fusion biopsy with PET-MRI and ultrasound was performed using transrectal access using ultrasound confirming infiltrating adenocarcinoma of the wall of the vas deferens, compatible with neoplastic prostate recurrence. The fusion image technique combines the real–time view of the US to the possibility of higher definition and higher specificity, methods more anatomical detail as tomography and magnetic resonance imaging, simultaneously. High resolution acquired in PET / MR associated with image fusion allows orientation procedures, even in areas of difficult access, with greater accuracy than conventional techniques.

Testosterone suppression is the standard treatment for advanced prostate cancer, and it is associated with side-effects that impair patients’ quality of life, like sexual dysfunction, osteoporosis, weight gain, and increased cardiovascular risk. We hypothesized that abiraterone acetate with prednisone (AAP) and apalutamide, alone or in combination, can be an effective hormonal therapy also possibly decreasing castration-associated side effects. Phase II, open-label, randomized, efficacy trial of abiraterone acetate plus prednisone (AAP) and Androgen Deprivation Therapy (ADT) versus apalutamide versus the combination of AAP (without ADT) and apalutamide. Key eligibility criteria are confirmed prostate adenocarcinoma; biochemical relapse after definitive treatment (PSA ≥ 4 ng/ml and doubling time less than 10 months, or PSA ≥ 20 ng/ml); newly diagnosed locally advanced or metastatic prostate cancer; asymptomatic to moderately symptomatic regarding bone symptoms. Patients with other histology besides adenocarcinoma or previous use of hormonal therapy or chemotherapy were excluded. There is an urgent need to study and validate regimens such as new hormonal agents that may add benefit to castration with an acceptable safety profile. We aim to evaluate if apalutamide in monotherapy or in combination with AAP is an effective and safety hormonal treatment that can spare patients of androgen deprivation therapy. This trial was registered in ClinicalTrials.gov on October 16, 2017, under Identifier: NCT02867020.

We report a case of a 43-year-old man who underwent a radical prostatectomy 3 years before the procedure (June 2015) for a locally advanced Gleason 7(4 + 3) prostate adenocarcinoma (pT3aN0), with negative surgical margins, followed by salvage radiotherapy. He also underwent antiandrogen therapy for biochemical relapse (bicalutamide) from October 2016 through May 2017, but prostate-specific antigen continued to rise (2.5 ng/mL [December 2017] and 3.3 ng/mL [February 2018]). At this point, he underwent a Ga-prostate-specific membrane antigen PET/CT, and after multidisciplinary discussion, the therapeutic option chosen was image-guided salvage cryoablation.

64 Background: LACOG0415 is a 3-arm randomized trial evaluating ADT with abiraterone acetate plus prednisone (ADT+AAP), apalutamide alone (APA) or apalutamide with AAP (APA+AAP) for patients with locally-advanced, high-risk biochemical recurrence or metastatic castration-sensitive prostate cancer (ASCO 2020). In this trial, ADT+AAP and APA+AAP achieved the primary endpoint of percentage of patients with PSA ≤ 0.2 ng/mL at week 25. Apalutamide alone showed a high PSA decline > 50% rate, but did not achieve the pre-specified PSA threshold. Here we report patient-reported outcome data using Functional Assessment of Cancer Therapy-Prostate (FACT-P). Methods: HRQoL was measured in the overall population using the FACT-P questionnaire, comprising 5 subscales: physical wellbeing (PWB), functional wellbeing (FWB), emotional wellbeing (EWB), social/family wellbeing (SFWB), and prostate cancer subscale (PCS). Scores for each patient were measured at baseline and every four weeks until week 25. Questionnaire completion was defined as ≥ 1 question answered at an assessment time point. Analysis of HRQoL change from baseline and deterioration included only patients with baseline and ≥ 1 postbaseline score. Differences greater than 10-points in FACT-P total score and differences greater than 3-points in PWB, FWB, EWB, SFWB, and PCS scores were considered clinically significant. The time-to-event endpoint was estimated by Kaplan-Meier method and compared by stratified log-rank test. Results: 128 patients were included in LACOG0415 trial and 122 of them completed the HRQoL assessments (ranging from 95.3% at baseline to 79.7% at week 25). FACT-P and all subscales scores were similar for all three arms at baseline. There were no meaningful differences in FACT-P scores at baseline and at week 25 between the 3 arms. The subscales scores also showed no statistically differences at baseline and at week 25. Time to FACT-P deterioration did not show any statistically difference between three arms ( P=0.3371). Conclusions: ADT free alternatives with APA alone or APA+AAP did not show meaningful differences in HRQoL in patients with advanced castration-sensitive prostate cancer compared to ADT+AAP. The short follow-up period limited the ability to explore differences in HRQoL after 25 weeks. Larger studies with longer follow-up are needed to further evaluate HRQoL with ADT-free strategies. Clinical trial information: NCT02867020. [Table: see text]

100 Background: Two PARP inhibitors (olaparib, rucaparib) are now FDA approved for mCRPC patients with mutations in BRCA1/2, but the relative efficacy of PARP inhibition in BRCA1- vs BRCA2-altered mCRPC is understudied. Methods: We conducted a multi-center retrospective analysis involving 11 academic sites. We collected genomic and clinical data from 123 BRCA1/2-altered mCRPC patients receiving PARP inhibitor treatment. The primary efficacy endpoint was PSA50 response rate (≥50% decline in PSA level). Secondary endpoints were PFS (clinical, radiographic or PSA progression, whichever occurred first) and overall survival (OS). We also captured information on other concurrent genomic alterations. We compared genomic characteristics and clinical outcomes among BRCA1- vs BRCA2-altered mCRPC. Results: A total of 123 patients (13 BRCA1, 110 BRCA2) were included. PARP inhibitors used were olaparib (n = 116), rucaparib (n = 3), talazoparib (n = 2) and veliparib (n = 2). All BRCA1 and 71% of BRCA2 patients had Gleason 8-10 disease. Compared to BRCA2 patients, BRCA1 patients were more likely to have received prior taxane chemotherapy (77% vs 62%). Age, baseline PSA, and prior enzalutamide/abiraterone treatment were similar between groups. PSA50 responses in BRCA1- vs BRCA2-altered patients were 38% vs 65% respectively ( P= 0.06). Median PFS in BRCA1 vs BRCA2 patients was 3.0 mo (95%CI, 0.9–5.1) vs 8.0 mo (95%CI, 5.3–10.6) respectively (HR 0.42, P= 0.01). Similarly, median OS in BRCA1 vs BRCA2 patients was 11.0 mo (95%CI, 9.9–12.1) vs 24.0 mo (95%CI, 18.2–29.8) respectively (HR 0.33, P= 0.005). There were roughly equal proportions of germline mutations (50% vs 45%) and biallelic mutations (31% vs 25%) in the BRCA2 and BRCA1 groups, respectively. There were numerically more TP53 mutations in the BRCA1 vs BRCA2 group (40% vs 29%, P= 0.45), but an equal number of mutations in other key genes ( PTEN, RB1 and AR). Conclusions: PARP inhibitor activity is diminished in BRCA1- vs BRCA2-altered mCRPC. In our cohort, this differential activity was not explained by mutation origin (germline vs somatic) or allelic status (mono- vs biallelic). These findings warrant validation.

5505 Background: ADT combined with AAP, APA, enzalutamide or docetaxel are among the standard treatment options to patients (pts) with hormone sensitive advanced/metastatic prostate cancer (PC). However, treatment-related adverse events (TRAEs) due to ADT impact negatively on the quality of life of these patients. Effective options with fewer TRAEs are required. Methods: LACOG 0415 is a phase II, randomized trial (1:1:1) evaluating the use of AA 1000mg po + prednisone 5mg po BID + ADT versus APA 240mg po alone versus AA 1000mg po + prednisone 5mg po BID + APA 240mg po in patients with advanced PC with non-castrate testosterone levels and indication of ADT (N+ or M+ or biochemical relapse combined with PSA ≥ 20 ng/ml or with PSA≥4 ng/ml and PSA doubling-time < 10 months). Stratification factors: metastatic disease (+/-). Primary endpoint was the percentage of pts who achieved PSA ≤ 0.2 ng/mL at Week 25, we estimated a PSA response rate of 65% in each of the three arms with a null hypothesis of 45%, power of 80% and alfa 5%, using Fleming one-stage method. Secondary endpoints were percentage of pts with ≥ 80% and ≥ 50% decline in PSA at week 25, radiographic progression-free survival (rPFS) and safety. Results: 128 patients were randomized between Oct 2017 and Apr 2019, and 122 pts were evaluable for PSA response. Median age was 69y (range, 53-88); most pts had ECOG PS0-1(99%). 17% of pts had biochemical relapse only, 9% N+ and 74% M+ disease. At week 25 the PSA was ≤ 0.2 ng/mL in 76% of pts in AAP+ADT arm, 59% in APA, and 80% in APA+AAP. All pts had a decline of ≥ 50% in PSA at week 25. 97% had a decline of ≥ 80% in PSA at week 25: 100% of pts in AAP+ADT arm, 95% in APA and 98% in APA+AAP. A total of 3 pts had clinical progressive disease, one in each arm. Two of them also had radiological progression at week 25, 1 pt in AAP+ADT arm and 1 pt in APA. TRAEs rates of any grade were 71% in AAP+ADT arm, 64% in APA, and 65% in APA+AAP. TRAEs rates of Grade≥3 were 12% in AAP+ADT arm, 9% in APA and 16% in APA+AAP. 9 pts (7%) discontinued the treatment before the week 25, 5(4%) of them due to toxicity: 1 pt from AAP+ADT, 2 pts from APA, and 6 pts from APA+AAP. Conclusions: The AAP+ADT and APA+AAP groups showed high effectiveness in terms of PSA response. Radiologic disease control and the decline of ≥ 80% in PSA at week 25 were similar among all treatment arms. APA alone had less toxicity. APA+AAP and APA alone are promising regimens in this setting. No new safety signal was detected in the study. Clinical trial information: NCT02867020 .

Objective To determine the overall survival of patients with advanced pancreatic cancer and evaluate factors that impact prognosis in a private cancer center.Methods Data from the Hospital Cancer Registry at Hospital Israelita Albert Einstein were retrospectively collected. The patients enrolled had metastatic cancer at diagnosis or earlier staging and subsequent recurrence. Cases of neuroendocrine tumors were excluded.Results A total of 65 patients were evaluated, including 63 with adenocarcinoma. The median overall survival for patients in all stages was 20.7 months (95%CI: 15.6-25.7), while the overall survival of metastatic disease was 13.3 months. Among the 33 cases with stage IV cancer, there was no evidence of a statistically significant association between median survival and CA19-9 dosage (p=0.212), tumor location (p=0.482), first treatment performed (p=0.337), lymphovascular invasion (p=0.286), and age (p=0.152). However, the number of lines of chemotherapy was significantly associated with survival (log-rank p=0.013), with an estimated median survival of 10.2 months for patients who received up to two lines of treatment and 23.5 months for those receiving more than two lines of chemotherapy.Conclusion The survival of patients treated was longer than that reported in the literature. The only statistically significant factor related to increased survival was higher number of lines of chemotherapy received. We believe that the higher socioeconomic status of patients surveyed in this study, as well as their greater access to treatment options, may have influenced their overall survival. Objetivo Determinar a sobrevida global dos pacientes com câncer pancreático avançado e avaliar fatores com impacto prognóstico em um centro de câncer privado.Métodos Foram coletados retrospectivamente os dados do Registro de Câncer do Hospital Israelita Albert Einstein. Os pacientes incluídos apresentaram câncer metastático ao diagnóstico ou em estádio mais precoce com recorrência subsequente. Os casos de tumores neuroendócrinos foram excluídos.Resultados Foram avaliados 65 pacientes, incluindo 63 com adenocarcinoma. A sobrevida global mediana dos pacientes em todos os estádios foi 20,7 meses (IC95%: 15,6-25,7), enquanto a sobrevida global de doença metastática foi de 13,3 meses. Entre os 33 casos com câncer em estádio IV, não houve evidência de associação estatisticamente significativa entre a sobrevida mediana e CA19-9 ao diagnóstico (p=0,212), localização do tumor (p=0,482), primeiro tratamento realizado (p=0,337), invasão vasculo-linfática (p=0,286) e idade (p=0,152). No entanto, o número de linhas de quimioterapia foi significativamente associado com a sobrevida (log-rankp=0,013), com uma sobrevida mediana estimada de 10,2 meses para os pacientes que receberam até duas linhas de tratamento e de 23,5 meses para os que receberam mais de duas linhas.Conclusão A sobrevida dos pacientes tratados foi maior do que o relatado na literatura. O único fator estatisticamente significativo relacionado à maior sobrevida foi maior número de linhas de quimioterapia recebidas. Acreditamos que o nível socioeconômico dos pacientes pesquisados neste estudo, assim como seu maior acesso a opções de tratamento, pode ter influenciado em sua sobrevivência global.

Context Currently, standard treatment of metastatic prostatic cancer (MPCa) is androgen-deprivation therapy (ADT). Recent studies suggested that local treatment of MPCa is related to increase of survival of those patients, as observed in other tumors. Objective To evaluate the impact of local treatment on overall survival and cancer specific survival in 3 and 5 years in patients with MPCa. Materials and Methods Systematic review and meta-analysis of population studies published at PubMed, Scielo, Lilacs, Cochrane and EMBASE databases until June 2016. Several large cohorts and Post-Roc studies were included, that evaluated patients with MPCa submitted to local treatment (LT) using radiotherapy (RDT), surgery (RP) or brachytherapy (BCT) or not submitted to local treatment (NLT). Results 34.338 patients were analyzed in six included papers, 31.653 submitted to NLT and 2.685 to LT. Overall survival in three years was significantly higher in patients submitted to LT versus NLT (64.2% vs. 44.5%; RD 0.19, 95% CI, 0.17-0.21; p

Introduction Prostate cancer still represents a major cause of morbidity, and still about 20% of men with the disease are diagnosed or will progress to the advanced stage without the possibility of curative treatment. Despite the recent advances in scientific and technological knowledge and the availability of new therapies, there is still considerable heterogeneity in the therapeutic approaches for metastatic prostate cancer. Objectives This article presents a summary of the I Brazilian Consensus on Advanced Prostate Cancer, conducted by the Brazilian Society of Urology and Brazilian Society of Clinical Oncology. Materials and Methods Experts were selected by the medical societies involved. Forty issues regarding controversial issues in advanced disease were previously elaborated. The panel met for consensus, with a threshold established for 2/3 of the participants. Results and Conclusions The treatment of advanced prostate cancer is complex, due to the existence of a large number of therapies, with different response profiles and toxicities. The panel addressed recommendations on preferred choice of therapies, indicators that would justify their change, and indicated some strategies for better sequencing of treatment in order to maximize the potential for disease control with the available therapeutic arsenal. The lack of consensus on some topics clearly indicates the absence of strong evidence for some decisions.

Oren Smaletz,1 Matias Chacón,2 Ludmila de Oliveira Koch,1 Daniela R de Carvalho Rocha,1 Fernanda C Cardoso1 1Department of Oncology, Hospital Israelita Albert Einstein, São Paulo, Brazil; 2Medical Oncology Department, Alexander Fleming Institute, Buenos Aires, Argentina Objective: To describe the clinical characteristics of Latin American patients with metastatic renal cell carcinoma (mRCC) who experienced a progression-free survival (PFS) for at least 15 months following treatment with sunitinib. Patients and methods: In this retrospective analysis, mRCC patients in two institutions in Latin America received sunitinib at a starting dose of either 50 mg/day for 4 weeks followed by 2 weeks off treatment (Schedule 4/2) in repeated 6-week cycles or sunitinib 37.5 mg on a continuous daily dosing schedule. Clinical characteristics, tolerability, and PFS data were collected. Results: Twenty-nine patients with long-term clinical benefit from sunitinib were identified between September 2005 and August 2009. Median PFS was 23 months (range: 15–54 months). Two of the 29 patients with prolonged PFS achieved a complete response and additional eleven had a partial response. Most patients were aged

TPS404 Background: Androgen deprivation therapy (ADT) combined with abiraterone (AA) or docetaxel are considered the standard of care (SOC) for patients with hormone sensitive (HS) advanced/ metastatic prostate cancer (PC) (STAMPEDE, LATITUDE, CHAARTED). Treatment that could delay disease progression with less toxicities and better quality of life is warrant. Recently, enzalutamide monotherapy showed a 92% PSA response in patients with advanced/ mestatatic prostate cancer without previous hormone therapy. Our study aims to evaluate the efficacy of apalutamide, a second-generation AR inhibitor, monotherapy or in combination with AA vs. SOC in advanced/metastatic HSPC. Methods: This is a phase II, open label, randomized trial evaluating the efficacy of AA 1000mg po qd plus prednisone 5mg po bid and ADT vs. Apalutamide 240mg po alone vs. AA and Apalutamide in patients with advanced or metastatic PC with non-castrate testosterone levels. Main eligible criteria are: 1. Histologically confirmed prostate adenocarcinoma; 2. Hormone naïve patients with indication to ADT in the following settings: Advanced loco-regional disease not amenable to curative local therapy (T3/4 or node positive); Biochemical relapse after primary treatment (surgery or radiotherapy) with PSA >= 4 ng/ml and rising with doubling time less than 10 months or PSA >= 20 ng/ml or N+ or M+; 3. Newly diagnosed metastatic disease; 4. Patient is symptomatic or moderately symptomatic; 5. Non-castration level of testosterone >= 230 ng/dL. The primary endpoint is undetectable PSA levels (below 0.2ng/mL) at week 25. The study aims for 65% of undetectable PSA at week 25 (power of 80% and alfa of 5%) and a total sample size of 126 patients. Secondary endpoints are PSA progression and PSA response (50% and 80%) at week 25, radiographic progression-free survival, safety, health quality of life (FACT-P) and correlation of serum androgen levels with response. As of October 17th, 2017 the study enrolled 1 patient and the recruitment is planned for 12 months in a total of 10 sites in Brazil. This trial is registered at Clinical trial information: NCT02867020.

Objective: To report the demographic data and clinical outcomes of non-small-cell lung cancer patients exposed to erlotinib in any line of treatment. Methods: This was a retrospective cohort study of nonsmall-cell lung cancer patients from a reference general hospital and a private oncology clinic, who received erlotinib from 2005 to 2011. Statistical analysis was performed and we evaluated demographic data and response to treatment, by correlating the results of this first cohort published in Brazil with results of current literature. Results: A total of 44 patients were included; 65.9% were diagnosed with adenocarcinoma, and 63.6% had metastatic disease. The mean age was 63.3 years. The median follow-up was 47.9 months. Epidermal growth factor receptor mutation screening was performed in 22.7% of patients (n=10), with mutation present in 30% of patients. The median overall survival was 46.3 months, and there was a higher probability of survival at 60 months for females compared to males (29.4% versus 15.8%; p=0.042). The other variables did not present significant statistical difference. Conclusion: We collected the largest cohort of patients with non-small-cell lung cancer who have used erlotinib in Brazil to date, and demonstrated that outcomes of patients treated at our clinic during the study period were consistent with the results of current literature in similar patients. RESUMO Objetivo: Relatar as características demográficas e a evolução de pacientes com neoplasia de pulmão de não pequenas células que receberam erlotinibe em qualquer linha de tratamento. Métodos: Coletamos retrospectivamente dados de pacientes portadores de neoplasia de pulmão de não pequenas células que receberam erlotinibe em qualquer linha de tratamento em um hospital geral de referência e em uma clínica particular de oncologia em São Paulo, no período de 2005 a 2011. Foi realizada a análise estatística e foram avaliados aspectos demográficos e resposta ao tratamento estabelecido, correlacionando os resultados dessa primeira coorte publicada no Brasil com resultados da literatura vigente. Resultados: Foram avaliados 44 pacientes, dos quais 65,9% eram portadores de adenocarcinoma e 63,6% tinham doença metastática. A média de idade foi de 63,3 anos. O seguimento mediano foi de 47,9 meses. A pesquisa de mutação do receptor do fator de crescimento epidérmico foi realizada em 22,7% dos pacientes (n=10), resultando positiva em 30% dos avaliados. A sobrevida global mediana foi de 46,3 meses, e observou-se uma probabilidade maior de sobrevida em 60 meses para o grupo feminino, quando comparado ao grupo masculino (29,4% versus 15,8%; p=0,042). As demais variáveis não apresentaram diferença estatística significativa. Conclusão: Coletamos a maior sequência de pacientes com neoplasia de pulmão de não pequenas células que fizeram uso de erlotinibe no Brasil até a data vigente e demonstramos que a evolução dos pacientes tratados no período avaliado teve resultados concordantes com os da literatura vigente em pacientes semelhantes.

Objectives The primary objective was to evaluate the clinical efficacy of hu3S193, a humanized monoclonal antibody against the Lewis-Y antigen, in patients with platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma. Secondary objectives were safety and pharmacokinetics. In addition, we sought to determine the potential interaction of clinical benefit and patient characteristics. Methods This two-stage, multicenter, single arm, phase II trial enrolled eligible patients to receive hu3S193 weekly at a dose of 20 mg/m2 intravenously for 8 weeks (1 cycle) to a maximum of 3 cycles. Efficacy was measured as clinical benefit rate (objective response or stable disease for at least 24 weeks). Results 26 of 31 patients were eligible for efficacy analysis. No complete/partial responses were observed. Six patients had stable disease for 24 + weeks [clinical benefit rate 23% (95% CI = 9.77%–46.71%)]. Median PFS was 8.4 weeks (95% CI = 6.0 to 16.1). Median PFS differed between patients with no ascites and no visceral disease and patients with ascites and/or visceral disease [16.1 vs. 8.1 weeks (p = 0.0058)]. The most commonly reported treatment-related adverse events were fatigue (19.3%) and nausea (16.2%). Allergic reactions occurred in 6 patients (5 with Grade 1/2; 1 with Grade 3). Conclusions Hu3S193 lacked sufficient activity in the first stage of the study to open enrollment to the second stage. However, based on the longer PFS in patients with no ascites and no visceral disease, consolidation strategies in platinum sensitive disease are currently being tested.

Os autores revisaram amplamente a literatura em relação aos fatores psiquiátricos envolvendo o câncer de mama. Dentro da linha de raciocínio mestra dos tratamentos cirúrgico e oncológico dessas pacientes, ressalta-se seu impacto sobre a saúde mental. Aspectos como possibilidades cirúrgicas, imagem corporal e impacto sobre auto-estima e sexualidade, tratamentos sistêmicos e conseqüências físicas, tais como fadiga, náuseas e vômitos, foram discutidos. As diferenças entre os grupos etários submetidos ao tratamento também foram relevadas, separando-se suas questões. Tópicos sobre a qualidade de vida sempre foram ressaltados. Questões sobre intervenções farmacológicas e psicoterapêuticas foram igualmente levantadas, incluindo medicina alternativa. The authors performed a broad literature review about psychiatric factors in breast cancer. Inside the master reasoning of the surgical and oncological treatments, an emphasis was made on heir impact over the mental health. Aspects like surgical possibilities and body image and its impact over the self-estime and sexuality and systemic treatments and their physical consequences, like fatigue, nausea and vomiting were discussed. The differences between the aged groups treated also were considered, separating their issues. Topics about Quality of Life was always considered. Questions about pharmacological and psychotherapeutical approach were considered too, including alternative medicine.

Os autores revisaram amplamente a literatura em relação aos fatores psiquiátricos envolvendo o câncer de mama. Dentro da linha de raciocínio mestra dos tratamentos cirúrgico e oncológico dessas pacientes, ressalta-se seu impacto sobre a saúde mental. Aspectos como possibilidades cirúrgicas, imagem corporal e impacto sobre auto-estima e sexualidade, tratamentos sistêmicos e conseqüências físicas, tais como fadiga, náuseas e vômitos, foram discutidos. As diferenças entre os grupos etários submetidos ao tratamento também foram relevadas, separando-se suas questões. Tópicos sobre a qualidade de vida sempre foram ressaltados. Questões sobre intervenções farmacológicas e psicoterapêuticas foram igualmente levantadas, incluindo medicina alternativa.The authors performed a broad literature review about psychiatric factors in breast cancer. Inside the master reasoning of the surgical and oncological treatments, an emphasis was made on heir impact over the mental health. Aspects like surgical possibilities and body image and its impact over the self-estime and sexuality and systemic treatments and their physical consequences, like fatigue, nausea and vomiting were discussed. The differences between the aged groups treated also were considered, separating their issues. Topics about Quality of Life was always considered. Questions about pharmacological and psychotherapeutical approach were considered too, including alternative medicine.

PURPOSE: To develop a pretreatment prognostic model for survival of patients with progressive metastatic prostate cancer after castration using parameters that are measured during routine clinical management. PATIENTS AND METHODS: Pretreatment clinical and biochemical determinants from 409 patients enrolled onto 19 consecutive therapeutic protocols from June 1989 through January 2000 were evaluated. The factors selected were age, Karnofsky performance status (KPS), hemoglobin (HGB), prostate-specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALK), and albumin. These factors were combined in an accelerated failure time regression model to produce a nomogram to predict median, 1-year, and 2-year survival. The nomogram was validated internally and externally using data from a multicenter randomized trial of suramin plus hydrocortisone versus hydrocortisone alone. RESULTS: The median survival of the entire group was 15.8 months (range, 0.9 to 77.8 months); 87% have died. In multivariable analysis, KPS, HGB, ALK, albumin, and LDH were significantly associated with survival (P < .05), whereas age and PSA were not. All seven factors were included in the nomogram. When applied to the external validation data set, the nomogram achieved a concordance index of 0.67. Calibration plots suggested that the nomogram was well calibrated for all predictions. CONCLUSION: A nomogram derived from pretreatment parameters that are measured on a routine basis was constructed. It can be used to predict the median, 1-year, and 2-year survival of patients with progressive castrate metastatic disease with reasonable accuracy. The information is useful to assess prognosis, guide treatment selection, and design clinical trials.

Estimating prognosis with patients with metastatic disease is important for patient counseling, guiding treatment selection, and assessing treatment outcomes. For patients with noncastrate metastatic disease, androgen ablation is considered first-line therapy, with upward of 80% of patients showing clinical benefit. For these patients, information about duration of response to hormones and overall survival is important. Most patients eventually relapse, at which point the mortality from cancer greatly exceeds that from other causes. This article focuses on prognostic models for patients with progressive noncastrate and castrate metastatic prostate cancer.

e17039 Background: Lewis-Y (LeY) antigen is a blood group related antigen expressed in 75% of OC. hu3S193 is a humanized anti-LeY IgG1 mAb with strong complement and antibody dependent cytotoxicity with clinical benefit shown in a phase II study in pts with platinum-resistant OC and small tumor burden. Improving progression free survival (PFS) in pts who achieve a 2CR is an unmet need. Methods: This phase II study accrued pts with relapsed OC, LeY expression by IHC, and a KPS ≥ 70% who had achieved a 2CR after 5-8 cycles of platinum doublet chemotherapy (chemoRx). Patients received intravenous infusions of hu3S193, 30mg/m2every 2 weeks starting ≤ 8 weeks after the last dose of chemoRx and continuing for 12 doses (24 weeks) or until disease progression or unacceptable toxicity. Primary endpoint was PFS with a sample size calculated to detect a 50% increase in PFS, compared to a historical value of 10.8 months. Secondary objectives were safety and pharmacokinetics (PK). Results: 29 pts were enrolled. Median age: 55 yrs (range 29-67); Median KPS: 90% (range 80-100); LeY expression by IHC (N): strong (20), weak (9); stage at initial diagnosis: I/II (2), III/IV (27); median CA-125 prior to 2CR chemoRx: 104 (range 9-514); chemoRx agents to achieve 2CR: paclitaxel/platin (21), liposomal doxo/carboplatin (8); median cycles of prior chemoRx to achieve a 2CR:6; median doses of hu3S193 delivered: 10 (range 10-12). Evaluable pts: 28 (1 pt did not have 2CR); median PFS: 11.8 months (95% CI: 10.6-13.9) while 3 pts achieved PFS of 25+ months. Grade 4 toxicities observed: none. Most frequent toxicities (any grade/grade 3): Nausea (16/2), Vomiting (15/3), Hypersensitivity (9/0). PK data will be presented. Conclusions: Despite the good tolerance and the longer PFS compared to historical control, this trial did not show a significant improvement with hu3S193 as a consolidative strategy in patients with 2CR in platinum-sensitive OC. Tumor molecular analysis of patients with long PFS may provide insight for future studies. Clinical trial information: NCT01137071.

Objectives In designing a Phase II trial, the acceptable clinical activity region for a new therapy is often developed using data from historically treated patients. This region incorrectly ignores the variability of this estimate, because the efficacy of the prior treatment lies somewhere around the estimate. The size of this interval is dependent on the sample size used. This report illustrates the use of a published method that accounts for this uncertainty and aids in the decision to proceed to a definitive trial. Methods A historical data set of low-risk patients with progressive castrate metastatic prostate cancer and a group of similar patients treated in a Phase II chemotherapy trial were used. The 1-year Kaplan-Meier estimate of survival was obtained for both. This approach uses the 75% upper confidence bound of the 1-year survival probability from the historical data set to define the lower limit of acceptable clinical activity. Use of this bound makes the approach more conservative, and hence the decision to proceed to a Phase III trial more difficult. Results In the low-risk historical patients, the 1-year Kaplan-Meier estimate of survival was 66.4% (75% upper confidence bound 71.0%). In the Phase II patients, the 1-year Kaplan-Meier estimate of survival was 89.5% (95% lower confidence bound 78.2%). Conclusions A hypothesis test using the 75% upper confidence bound to define the lower limit of acceptable clinical activity demonstrates that the 1-year survival probability on Taxol/estramustine/carboplatin is greater than that of the historical population, and hence should be taken into a definitive trial. The design provides investigators increased confidence in making this decision.

Purpose: To investigate the safety and feasibility of rapid androgen cycling for men with progressive prostate cancer. Experimental Design: Schedule 1 included a 4-week induction of androgen depletion, followed by 4-week treatment cycles of a monthly gonadotropin-releasing hormone agonist, testosterone on days 1 to 7, and an estrogen patch on days 8 to 21. Schedule 2 included a 12-week induction of androgen depletion followed by 4-week cycles of gonadotropin-releasing hormone agonist and testosterone, but no estrogens for patients with a prostate-specific antigen (PSA) nadir Results: Thirty-six patients were treated; 27 were evaluable after cycling, of whom 8 of 12 (67%) and 9 of 15 (60%) on schedules 1 and 2, respectively, reached the end point. Five patients with PSA >1 ng/mL following induction did not cycle. No patient progressed radiographically or clinically during cycling. Three posttherapy PSA patterns were observed: a decline followed by a rapid increase in trough levels, a sustained decline with a plateau at a detectable nadir, and a decline to an undetectable nadir. Mean testosterone levels were castrate at the time of trough and in the normal physiologic range following androgen repletion. Major toxicities included grades 1 and 2 fatigue, hepatitis, gynecomastia, and hot flashes. Conclusions: Rapid hormonal cycling is feasible and well tolerated, and successive declines in PSA troughs are achievable. Although the sample size was small, the proportion of patients achieving declining PSA at the end of six cycles was comparable with that reached with continuous androgen depletion therapy.

To quantify the frequency of potential drug interactions unrelated to chemotherapy in cancer patients admitted to our institution, and to define risk factors for such interactions.Charts of 100 consecutive hospitalized cancer patients were reviewed. Patients receiving chemotherapy and/or hormone therapy were excluded, as were patients admitted for intensive care. Drug-drug interactions were screened with Drug Interaction Facts software, and manually by the authors. Potential interactions were graded by levels of severity (severe, moderate, minor) and significance (one to five, with one representing the highest level of evidence).The median age of the patients was 67 years, and the length of hospital stay and the number of drugs per patient were 6 days and eight drugs, respectively. In 63 patients 180 potential interactions were detected. Of the potential interactions, 18.3% were severe, 56.7% were moderate, and 25% were minor. Approximately 7%, 18% and 13% of potential interactions were graded as level 1, 2 and 3, respectively. In multivariate analysis, prescriptions with eight or more drugs (P=0.0004) and six or more days of hospital stay (P=0.014) were independent risk factors for potential interactions.Potential drug interactions are common among hospitalized cancer patients. Length of hospital stay and number of prescribed drugs are risk factors.

BACKGROUND Preclinical and clinical data have suggested that high-dose calcitriol (1,25-dihydroxycholecalciferol) has activity against prostate carcinoma. Pulse-dosed calcitriol and dexamethasone may maximize tolerability and efficacy. The authors examined the toxicity of pulse-dosed calcitriol with zoledronate and with the addition of dexamethasone at the time of disease progression. METHODS Patients with progressive prostate carcinoma were eligible for the current study. In cohorts of 3–6 patients, calcitriol was administered for 3 consecutive days per week, starting at a dose of 4 μg per day. Doses were escalated to 30 μg per day. Intravenous zoledronate (4 mg) was administered monthly. Dexamethasone could be added to the regimen at disease progression. Toxicities, markers of bone turnover, plasma calcitriol levels, and clinical outcomes were recorded. RESULTS Thirty-one patients were treated in cohorts that were defined by the calcitriol dose administered (4, 6, 8, 10, 14, 20, 24, or 30 μg). Seven patients received dexamethasone. Three patients had their doses reduced due to calcium-related laboratory findings. Patients tolerated therapy well, even in the 30 μg cohort; therefore, a maximum tolerated dose was not defined. Peak plasma levels observed in the 24 μg and 30 μg cohorts ranged from 391 to 968 pg/mL. Minimal antitumor effects were observed. CONCLUSIONS Calcitriol was well tolerated at doses up to and including 30 μg 3 times per week in combination with intravenous zoledronate 4 mg monthly, with or without dexamethasone, in patients with progressive prostate carcinoma. Peak plasma levels in the 24 μg and 30 μg cohorts were greater than the levels associated with antitumor effects preclinically. Due to the cumbersome dosing schedule and the lack of significant activity observed, Phase II trials of this regimen are not planned. Cancer 2004. © 2004 American Cancer Society.

Background: Several trials have demonstrated that the response proportions to microtubule agents in patients with prostate cancer are increased by the addition of estramustine phosphate (EMP). The epothilone B analog BMS-247550 is a novel microtubule agent that has shown activity in taxane-resistant tumors. We conducted a dose-escalation study to determine a safe dose of BMS-247550 to combine with EMP in patients with metastatic prostate cancer. Patients and methods: Chemotherapy-naive patients with castrate-metastatic prostate cancer were treated with intravenous BMS-247550 and oral EMP (280 mg three times daily for 5 days) every 3 weeks. Results: Thirteen patients were treated at two dose levels (35 and 40 mg/m 2 ). Three of six patients treated at 40 mg/m 2 developed grade 4 neutropenia, establishing 35 mg/m 2 as the maximum-tolerated dose. Significant peripheral neuropathy (grade ≥2) was related to dose level and infusion rate. A decline in prostate-specific antigen (PSA) of ≥50% was seen in 11 of 12 evaluable patients (92%) (95% confidence interval 76% to 100%). There were objective responses in soft tissue (57%) and bone metastasis (40%). Conclusions: The phase II dose of BMS-247550 combined with EMP is 35 mg/m 2 over 3 h every 3 weeks. This combination is safe and ≥50% post-therapy declines in PSA were seen in 11 of 12 patients (92%).

e15537 Background: PC-RPLND plays an important role in the management of residual masses of advanced NSGCT of the testis. Teratomatous elements in the primary tumor is a risk factor for teratoma in...

465 Background: Prospective studies with sunitinib in mRCC have shown median progression-free survival (mPFS) of 11 months (first line) and 8.3 months (second line). In order to identify patients with LTB with SU, we describe the clinical characteristics of patients with mRCC treated with SU with an mPFS of 15 months or more. Methods: This is a retrospective chart review of patients with mRCC treated with SU in two hospitals, Alexander Fleming Institute Buenos Aires in Argentina and Hospital Israelita Albert Einstein in Sao Paulo, Brazil. Inclusion criteria included patients treated with SU who had a PFS of at least 15 months. Results: Between September 1995 and August 2009, 29 cases were identified. Patient demographics were: median age of 56 years, 65% male, 96% with previous nephrectomy, Eastern Cooperative Oncology Group performance status (PS) of either 0 (52%) or 1 (48%), 93% had clear cell histology, 69% received prior systemic therapy, and 78% had ≤ 2 metastatic sites (mostly in the lungs, liver and bone). Patients were started on SU 50 mg 4 weeks on treatment/2 weeks off treatment (4/2) (n=26) or 37.5 mg 6 weeks continuous dosing (n=3). For those patients starting on 4/2, dose reduction was necessary in 59% of the patients to maintain SU therapy. Median duration of therapy was 23.7 months. During treatment, 24 patients (83%) developed hypertension. Response rates were as follows: complete response 7% (n=2), partial response 38% (n=11), stable disease 52% (n=15); data missing for one patient. Conclusions: LTB is seen in patients who are young, have good performance status, and either 1 or 2 metastatic sites. Dose reductions are common in order to maintain treatment while benefiting from SU. Treatment with SU as either first- or second-line therapy did not appear to influence outcome. Hypertension is a common finding and serves as a predictive marker during treatment, but study limitations preclude the identification of pre-treatment predictive factors.