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INTRODUCTION AND OBJECTIVE:The phase 3 TITAN and SPARTAN studies demonstrated improved outcomes with the addition of apalutamide (APA) to androgen deprivation therapy (ADT); outcomes included prolo...

INTRODUCTION AND OBJECTIVE:The phase 1/2 KEYNOTE-365 study (NCT02861573) previously showed that pembro+olaparib was associated with antitumor activity and acceptable safety in molecularly unselecte...

INTRODUCTION AND OBJECTIVES:SPARTAN, a randomized phase 3 placebo (PBO)-controlled study in pts with high-risk nmCRPC, demonstrated that APA added to androgen deprivation therapy (ADT) prolonged me...

INTRODUCTION AND OBJECTIVES:APA, a next-generation androgen receptor inhibitor, added to androgen deprivation therapy (ADT) improved MFS by > 2 years (median 40.5 vs 16.2 mo; p < 0.0001) in high-ri...

Translocation renal cell carcinomas represent a distinct clinicopathological entity. Studying the natural history, biological behavior and potential prognostic factors are crucially warranted.We selected 54 patients with renal cell carcinoma with positive nuclear transcription factor E3 and transcription factor EB expression from the Juvenile RCC Network. Recurrence-free survival and overall survival were assessed.Median patient age was 24 years (range 1 to 64) and the male-to-female ratio was 1:1.4. At diagnosis 35 patients (65%) had local disease while 19 (35%) presented with distant metastases. The latter patients were older (median age 36 years) and predominantly male (male-to-female ratio 2) whereas the former group had a median age of 16 years and a male-to-female ratio of 1:2.5. Overall 36 patients underwent complete tumor resection and of these 8 had recurring cancer. On univariate analysis only lymph node involvement and American Joint Committee on Cancer stage were associated with poor recurrence-free survival. When stratified according to lymph node status age 25 years or older was found to predict relapse (p = 0.03). With a median followup of 19.2 months (range 1 to 58) 3-year overall survival was 14.3% in patients with distant metastasis and 70.6% in those without distant metastasis. Distant metastasis developed in the 2 patients with ASPSCR1-TFE3 fusion vs 1 of 11 with other fusion genes.Transcription factor E3 and transcription factor EB renal cell carcinoma display different clinical behavior according to gender and age. Lymph node involvement represents the only factor that predicts recurrence. ASPSCR1-TFE3 might be the most aggressive among the transcription factor E3 fusion genes.

Sorafenib and sunitinib are 2 tyrosine kinase inhibitors that were recently approved for renal cell carcinoma. In many patients sequential administration of the 2 drugs occurs because of the lack of sustained efficacy of the first agent. We determined the efficacy and safety of sequential administration.To determine whether cross-resistance occurs between these 2 drugs we analyzed the outcome in 90 consecutive patients with renal cell carcinoma from 4 sites in France who had received the 2 drugs sequentially. All patients received sorafenib followed by sunitinib or vice versa. From 2003 to 2006, 68 patients received sorafenib, while 22 received sunitinib first.In the sorafenib-sunitinib group median progression-free survival was 26 weeks with sorafenib and 28 with sunitinib. In the sunitinib-sorafenib group median progression-free survival was 22 weeks with sunitinib and 17 with sorafenib. Median overall survival was 135 weeks in the sorafenib-sunitinib group and 82 weeks in the sunitinib-sorafenib group (HR 0.49, 95% CI 0.16 to 0.96, p = 0.04). The average duration of sequential administration was 61 and 49 weeks, respectively, in the sorafenib-sunitinib and sunitinib-sorafenib groups. Each sequence was well tolerated and no increase in grade 3-4 toxicity was observed.Overall this retrospective study supports the conclusion of the lack of absolute cross-resistance between tyrosine kinase inhibitors. In this renal cell carcinoma population sorafenib followed by sunitinib was associated with longer survival than sunitinib followed by sorafenib. However, this observation needs further confirmation.

Collecting duct carcinoma of the kidney is a rare and aggressive neoplasm of the distal collecting tubules for which there is no established treatment. Since the histology of collecting duct carcinoma is similar to that of urothelial carcinoma, the standard chemotherapy regimen defined by a gemcitabine and platinum salts combination was prospectively investigated in patients with metastatic collecting duct carcinoma.A total of 23 patients with metastatic collecting duct carcinoma with no prior systemic chemotherapy were treated with 1,250 mg/m(2) gemcitabine on days 1 and 8 plus 70 mg/m(2) cisplatin or carboplatin (AUC 5) in patients with renal insufficiency on day 1. The drugs were repeated every 21 days for 6 cycles according to toxicity and efficacy. The objective response rate was the primary end point.There were 1 complete and 5 partial responses for an objective response rate of 26% (95% CI 8 to 44). Median progression-free and overall survival was 7.1 (95% CI 3 to 11.3) and 10.5 months (95% CI 3.8 to 17.1), respectively. Toxicity was mainly hematological with grade 3-4 neutropenia and thrombocytopenia in 52% and 43% of patients, respectively. The severity of granulocytopenia and the number of metastatic sites were associated with overall survival on univariate and multivariate analyses.To our knowledge this is the first prospective, multicenter, phase II study showing that the platinum salts combination is an active and safe regimen as first line treatment in patients with metastatic collecting duct carcinoma. This platinum based chemotherapy should be considered the standard regimen in these patients.

Fred Saad*, Montr eal, Canada; Thian Kheoh, Margaret K. Yu, Los Angeles, CA; Matthew R. Smith, Boston, MA; Eric J. Small, San Francisco, CA; Peter F. A. Mulders, Nijmegen, Netherlands; Karim Fizazi, Villejuif, France; Dana Rathkopf, New York, NY; St ephane Oudard, Paris, France; Howard I. Scher, New York, NY; Joaquim Bellmunt, Mary-Ellen Taplin, Boston, MA; Ian D. Davis, Victoria, Australia; Dirk Schrijvers, Antwerp, Belgium; Andrew Protheroe, Oxford, United Kingdom; Arturo Molina, Menlo Park, CA; Thomas W. Griffin, Los Angeles, CA; Johann S. de Bono, Sutton, United Kingdom; Charles J. Ryan, San Francisco, CA

Collecting duct carcinoma (CDC) of the kidney is a rare variant that is associated with an extremely poor prognosis. We report our experience with this variety of cancer in the last 9 years.From 1993 to 2002, 9 patients with CDC were treated at our institution. The diagnosis of CDC was made by a nephrectomy specimen in 8 cases and by renal biopsy in 1. Tumor characteristics, and patient treatment and outcome are reported.At presentation 1 T1N0M0, 1 T3N0M0, 3 T3N+M0 and 4 T3N+M+ tumors were seen. Mean followup was 13.6 months. Five patients received no complementary treatment. The patient with the T1N0M0 tumor remained free of disease 13 months after nephrectomy and the one with T3N0M0 tumor remained free of disease at 17 months. A patient with a T3N+M+ tumor experienced progression at 1 month, local recurrence at 17 months and was then lost to followup. The 2 other patients with T3N+M0 and T3N+M+ disease, respectively, progressed rapidly and were lost to followup after 5 months. One patient with a T3N+M0 neoplasm received immunotherapy and died after 24 months, while the other with T3N+M0 disease was treated with oral prednisolone and died after 5 months. Finally, 2 patients with T3N+M+ disease received chemotherapy, consisting of 1,250 mg/m2 gemcitabine on days 1 and 8, and 70 mg/m2 cisplatin on day 1. Each patient achieved an objective response after 3 chemotherapy cycles and remained disease-free 27 and 9 months after nephrectomy, respectively.CDC is an aggressive variety of kidney neoplasm that is often associated with nodal and visceral metastases at presentation. Our data suggest that combined gemcitabine and cisplatin chemotherapy may be the best therapeutic option for patients with this tumor.

Matthew Smith*, Boston, MA; Fred Saad, Montreal, Canada; Neal Shore, Myrtle Beach, SC; Stephane Oudard, Paris, France; Kurt Miller, Berlin, Germany; Bertrand Tombal, Bruxelles, Belgium; Paul Sieber, Lancaster, PA; Karim Fizazi, Villejuif, France; Peter Van Veldhuizen, Kansas City, MO; Ronaldo Damiao, Rio de Janeiro, Brazil; Gavin Marx, Wahroonga, Australia; Juan Morote, Barcelona, Spain; Amy Feng, Roger Dansey, Carsten Goessl, Thousand Oaks, CA

INTRODUCTION AND OBJECTIVES: Men with castrate-resistant prostate cancer (CRPC) who develop bone metastases may experience pain that seriously impacts function and quality of life. A recent randomized phase 3 trial demonstrated superiority of denosumab to zoledronic acid (ZA) for prevention of skeletal complications of bone metastases in men with CRPC. Here we report the results of pain interference (PI) with daily functioning. METHODS: Patients with CRPC and 1 site of bone metastasis received either subcutaneous (SC) denosumab 120 mg and intravenous (IV) placebo (n 950) or IV ZA 4 mg and SC placebo (n 951) every 4 weeks. PI with daily functioning (overall; activity [general activity, walking, work]; and affect [mood, enjoyment of life, relations with others]) was assessed using the Brief Pain Inventory at baseline and before each monthly visit. Responses on a scale of 0 (no) to 10 (complete) interference were analyzed for all randomized patients through month 18, when 50% of patients had dropped out due to death, disease progression, or consent withdrawal. RESULTS: Overall, from month 1 to 18, the average relative proportion of patients who reported increased PI ( 2 point increase) was 5% greater in the ZA group than in the denosumab group. Among patients with no/mild pain at baseline (56%), 13% more in the ZA group had increased PI relative to denosumab. For PI activity and affect domains, overall relative proportional differences between ZA and denosumab were 6% and 5%, respectively, favoring denosumab. For patients with no/mild pain at baseline, the average relative proportional differences for both domains were 13% each (Figure: Activity). CONCLUSIONS: In this trial of men with CRPC and bone metastases, denosumab was associated with a reduced incidence of increased pain interference over the study period compared with ZA, and this was further accentuated in patients with no or mild pain at baseline. Effective management of the impact of pain on patients’ daily lives is important to minimize patients’ distress and maintain quality of life. Preservation of physical function and mood, particularly in the early stages of treatment, contributes substantially towards this goal.