A phase II study of retifanlimab, a humanized anti-PD-1 monoclonal antibody, in patients with solid tumors (POD1UM-203).

BACKGROUND: POD1UM-203, an open-label, multicenter, phase II study, evaluated retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in patients with selected solid tumors where immune checkpoint inhibitor therapies have previously shown efficacy. PATIENTS AND METHODS: Eligible patients (≥18 years) had measurable disease and included unresectable or metastatic melanoma, treatment-naive metastatic non-small-cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression (tumor proportion score ≥50%), cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (UC) with PD-L1 expression (combined positive score ≥10%), or treatment-naive locally advanced/metastatic clear-cell renal cell carcinoma (RCC). Retifanlimab 500 mg was administered intravenously every 4 weeks as a 30-min infusion. The primary endpoint was investigator-assessed overall response rate. RESULTS: Overall, 121 patients (35 melanoma, 23 NSCLC, 29 UC, 34 RCC) were enrolled and treated. The overall response rate [95% confidence interval (CI)] was 40.0% (23.9-57.9) in the melanoma cohort, 34.8% (16.4-57.3) in the NSCLC cohort, 37.9% (20.7-57.7) in the UC cohort, and 23.5% (10.7-41.2) in the RCC cohort. Median duration of response was 11.5 months (95% CI 2.2-not reached) in the UC cohort, and was not reached in the other cohorts. Retifanlimab safety was consistent with previous experience for PD-(L)1 inhibitors. CONCLUSIONS: Retifanlimab demonstrated durable antitumor activity in patients with melanoma, NSCLC, UC, or RCC. The efficacy and safety of retifanlimab were as expected for a PD-(L)1 inhibitor. These data support further study of retifanlimab in solid tumors.

Gastrointestinal metastases in renal cell carcinoma: A retrospective multicenter GETUG (Groupe d'Étude des Tumeurs Uro-Génitales) study.

BACKGROUND: Among patients with renal cell carcinoma (RCC), bone and visceral metastases have a poor prognosis, while endocrine gland metastases have a more favorable prognosis. Gastrointestinal metastases (GIMs) are rare, and their prognosis is still poorly understood. OBJECTIVES: To report clinical presentations, patient characteristics, therapeutic strategies, and prognosis of GIMs from RCC. METHODS: We retrospectively collected data from RCC patients presenting GIMs, in 10 French GETUG centers, between 2000 and 2021. RESULTS: We identified 74 patients with 87 GIMs, mostly gastric or duodenal. The median age at GIM diagnosis was 69 years and 76% of patients already had other metastases. GIMs occurred after a median duration of 5.4 years (IC95%=[4.2-7.1]) and 1.9 years (IC95%=[1.2-3.8]) from RCC diagnosis and first metastasis, respectively. GIMs were symptomatic in 52 patients (70%), with anemia in 41 patients (55%) and/or gastrointestinal bleeding in 31 patients (42%). Only 22 asymptomatic patients (30%) were fortuitously diagnosed. GIM management consisted of systemic treatment only in 29 GIMs (33%), local treatment only in 23 GIMs (26%), and both local and systemic treatment in 18 GIMs (21%). For 17 GIMs (20%), there was no therapeutic modification. After diagnosis of GIM, median overall survival was 19 months. CONCLUSION: We report the largest retrospective cohort of GIMs in RCC patients. They should be suspected in case of anemia or gastrointestinal bleeding in any patient with a history of RCC. Their management varies widely depending on their location in the digestive tract and whether or not they are symptomatic.

Urachal carcinoma: a large retrospective multicentric study from the French Genito-Urinary Tumor Group.

Introduction: Urachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of UrC is adenocarcinoma. UrC develops from an embryonic remnant, and is frequently diagnosed in advanced stage with poor prognosis. The treatment is not standardized, and based only on case reports and small series. This large retrospective multicentric study was conducted by the French Genito-Urinary Tumor Group to gain a better understanding of UrC. Material and Methods: data has been collected retrospectively on 97 patients treated at 22 French Cancer Centers between 1996 and 2020. Results: The median follow-up was 59 months (range 44-96). The median age at diagnosis was 53 years (range 20-86), 45% were females and 23% had tobacco exposure. For patients with localized disease (Mayo I-II, n=46) and with lymph-node invasion (Mayo III, n=13) median progression-free-survival (mPFS) was 31 months (95% CI: 20-67) and 7 months (95% CI: 6-not reached (NR)), and median overall survival (mOS) was 73 months (95% CI: 57-NR) and 22 months (95% CI: 21-NR) respectively. For 45 patients with Mayo I-III had secondary metastatic progression, and 20 patients were metastatic at diagnosis. Metastatic localization was peritoneal for 54% of patients. Most patients with localized tumor were treated with partial cystectomy, with mPFS of 20 months (95% CI: 14-49), and only 12 patients received adjuvant therapy. Metastatic patients (Mayo IV) had a mOS of 23 months (95% CI: 19-33) and 69% received a platin-fluorouracil combination treatment. Conclusion: UrC is a rare tumor of the bladder where patients are younger with a higher number of females, and a lower tobacco exposure than in standard urothelial carcinoma. For localized tumor, partial cystectomy is recommended. The mOS and mPFS were low, notably for patients with lymph node invasion. For metastatic patients the prognosis is poor and standard therapy is not well-defined. Further clinical and biological knowledge are needed.

[Does the announcement of cancer at the time of Non Muscle-Invasive Bladder Cancer diagnosis affect quality of life and adherence of patients? Data from the French prospective cohort VICAN]. / L'annonce du cancer au diagnostic de Tumeur de vessie non infiltrant le muscle modifie-t-elle la qualité de vie et l'observance des patients ? Données de la cohorte prospective française VICAN.

INTRODUCTION: The information provided at the time of diagnosis of Non Muscle-Invasive Bladder Cancer (NMIBC) is highly variable. Well-informed patient are more involved in shared decisions. The objective of our study was to assess the information perceived by the patient at the time of NMIBC diagnosis and its impact on quality of life. METHODS: The VICAN french cohort involved a representative sample of 4174 cancer patients and 5 years survivors. Patients reported outcomes (PROs) were collected by phone and self-questionnaire. Among the 118 NMIBC patients, the term used to define the pathology at diagnosis was prospectively evaluated. The impact on quality of life (using SF-12, EORTC-QLQ-C30 and HAD scale) and on adherence to the care protocol (endoscopic monitoring) has been assessed. RESULTS: Only 26.8% of patients reported hearing the word « Cancer ¼ at the time of NMIBC diagnosis. Conversely, 73.2% of them reported others terms, including « Tumor ¼ (22%), « Polyp ¼ (24%), and « Carcinoma ¼ (17.1%). There was no difference in terms of physical, mental quality of life and anxiety, regardless of the term used. Adherence to the follow-up endoscopic protocol was better in the group of patients hearing the word "Cancer". CONCLUSION: Three quarters of patients treated for NMIBC did not integrate the concept of « Cancer ¼ at the time of diagnosis. Quality of life and anxiety did not differ significantly depending on the term used at diagnosis. However, adherence to care protocol appears to be higher when using the word "Cancer". LEVEL OF EVIDENCE: 3.

Efficacy and correlative analyses of avelumab plus axitinib versus sunitinib in sarcomatoid renal cell carcinoma: post hoc analysis of a randomized clinical trial.

BACKGROUND: Among patients with advanced renal cell carcinoma (RCC), those with sarcomatoid histology (sRCC) have the poorest prognosis. This analysis assessed the efficacy of avelumab plus axitinib versus sunitinib in patients with treatment-naive advanced sRCC. METHODS: The randomized, open-label, multicenter, phase III JAVELIN Renal 101 trial (NCT02684006) enrolled patients with treatment-naive advanced RCC. Patients were randomized 1 : 1 to receive either avelumab plus axitinib or sunitinib following standard doses and schedules. Assessments in this post hoc analysis of patients with sRCC included efficacy (including progression-free survival) and biomarker analyses. RESULTS: A total of 108 patients had sarcomatoid histology and were included in this post hoc analysis; 47 patients in the avelumab plus axitinib arm and 61 in the sunitinib arm. Patients in the avelumab plus axitinib arm had improved progression-free survival [stratified hazard ratio, 0.57 (95% confidence interval, 0.325-1.003)] and a higher objective response rate (46.8% versus 21.3%; complete response in 4.3% versus 0%) versus those in the sunitinib arm. Correlative gene expression analyses of patients with sRCC showed enrichment of gene pathway scores for cancer-associated fibroblasts and regulatory T cells, CD274 and CD8A expression, and tumors with The Cancer Genome Atlas m3 classification. CONCLUSIONS: In this subgroup analysis of JAVELIN Renal 101, patients with sRCC in the avelumab plus axitinib arm had improved efficacy outcomes versus those in the sunitinib arm. Correlative analyses provide insight into this subtype of RCC and suggest that avelumab plus axitinib may increase the chance of overcoming the aggressive features of sRCC.

[Safety of Hyperthermic IntraVEsical Chemotherapy (HIVEC) for BCG Unresponsive Non-Muscle Invasive Bladder Cancer Patients]. / Tolérance de la thermo-chimiothérapie par HIVEC® chez les patients réfractaires au BCG.

INTRODUCTION: There is increasing evidence that Hyperthermic Intravesical Chemotherapy is an effective treatment for non-muscle invasive bladder cancer (NMIBC). HIVEC (COMBAT BRS system) is an innovative hyperthermia delivering device. The aim of our study is to evaluate tolerance and safety of HIVEC in patients with BCG-refractory NMIBC. MATERIALS AND METHODS: In this study, we included 22 patients between January 2017 and April 2018. The treatment consisted in a weekly instillation of Hyperthermic Mitomycin for a total of 6 weeks, with a follow-up every 3 months. In order to evaluate the tolerance, patients filled a questionnaire before each instillation. We analyzed collected data to evaluate safety and efficiency of the treatment after one year. RESULTS: Among 22 patients included, no patient suffered from severe side effects. The minor side effects reported were : urinary urgency (40,1 %), urinary pain (40,1%), macroscopic hematuria (4,5%). The IPSS score didn't significantly varied before and after instillations (mean IPSS: 10.8 versus 10.1, p=0.77). The mean follow-up was 11.2 months. The recurrence rate was 27,3% with an average time to recurrence of 7.36 months. Two patients (9.1%) presented a progression to muscle-invasive disease. Four patients (18,2%) had a radical cystectomy. CONCLUSION: Hyperthermic Mitomycin using the HIVEC® device is a rather safe and well tolerated treatment. Efficiency remains partial as 27.3% of patients experienced recurrence during the first year. These data should be confirmed by prospective multicentric studies.

[Is a routine second transurethral resection of the bladder still necessary after hexaminolévulinate photodynamic diagnosis-assisted TURBT?] / La résection transurétrale de vessie de réévaluation est-elle toujours nécessaire en cas de primo-résection sous luminofluorescence par hexaminolévulinate ?

OBJECTIVES: The aim of our study was to assess the impact of blue light cystoscopy with hexaminolevulinate on residual tumor rates at second-look transurethral resection of the bladder (TURB). MATERIAL AND METHODS: Among all patients undergoing TURB in our center between 2012 and 2017, 52 patients had a second-look after a first complete TURB with a delay<3months. We compare patients with standard white light cystoscopy/TURB then second-look blue light cystoscopy/re-TURB (group A, n=30) and patients with blue light cystoscopy/TURB at the initial procedure then white light cystoscopy/re-TURB (group B, n=22). The residual tumor rates at second-look, restaging and changing in therapeutic strategy, as well as recurrence free survival and progression rate were compared. RESULTS: Residual tumor at the time of second-look cystoscopy was detected in 42.3% of cases in our cohort, with a significant difference between the two groups (63.3% in group A versus 0% in group B, <0.001). In group A, 16.7% (5/30) of patients had upstaging and/or upgrading at second-look cystoscopy, resulting in a change in therapeutic strategy in most cases (4/5) while none upstaging was observed in group B. In multivariate analysis, the use of luminofluorescence at the first TURB was the only independent predictive factor of residual tumor (P=0.0031). CONCLUSION: The quality of the initial TURB, when performed by using blue light cystoscopy, had a significant impact on the rate of residual tumor at the second-look resection and could modify therapeutic strategy of NMIBC. LEVEL OF EVIDENCE: 4.

[The REVELA13 observatory to study new cases of bladder tumor among women living in Bouches-du-Rhône county]. / Rôle de l'observatoire REVELA13 dans l'épidémiologie des tumeurs de vessie des femmes dans les Bouches-du-Rhône.

INTRODUCTION: The REVELA13 observatory is a unique epidemiological tool listing the new cases of kidney tumors, bladder tumors and acute leukaemias in the Bouches-du-Rhône county (France). Aim was to exploit for the first time data from this observatory regarding new cases of bladder tumors≥T1 in women from 2012 to 2014. MATERIALS: This epidemiological study was observational and descriptive. Fifteen non-nominative variables from the REVELA13 database were analyzed in order to describe the clinical and pathological characteristics of the incident cases as well as their spatial and temporal distribution. The incidence rates expressed in new cases per year per 100000 inhabitants were standardized on the world age, calculated with 95 % confidence intervals and compared to national estimates for the same period. RESULTS: Incident bladder tumor cases were recorded in 291 women, corresponding to a standardized incidence on the world age of 3.85 [3.32-4.37] new cases per year per 100,000 population, 54 % higher than the national estimates of 2012 and 2015. Median age of diagnostic was 75.9 years. Sex ratio was 19.41 % (W/M). Tumors were predominantly non-muscle-invasive (52 %), high grade (69 %) and without associated carcinoma in situ (Cis) (49 %). The two most affected territories were Marseille and Aubagne-La Ciotat. CONCLUSION: The REVELA13 observatory has improved our epidemiological knowledge on female bladder tumors in Bouches-du-Rhône county and highlighted a local over incidence. LEVEL OF EVIDENCE: 3.

Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer.

Background: A nivolumab monotherapy flat-dosing regimen of 480 mg every 4 weeks (Q4W) has been approved in several markets, including the United States, Canada, and European Union, as an alternative dosing regimen for several indications. Approvals of this Q4W regimen were based on population pharmacokinetic (PK) analyses, established flat exposure-response relationships, and clinical safety. The objective of this study was to compare the PK exposure of 480 mg Q4W with 3 mg/kg every 2 weeks (Q2W) and 240 mg Q2W using modeling and simulation, and to evaluate clinical safety of the Q4W regimen. Patients and methods: Nivolumab PK exposure for the 480 mg Q4W schedule was simulated for 3817 patients across multiple tumor types and compared with those for the 3 mg/kg Q2W and 240 mg Q2W schedules. The safety profile of the Q4W schedule was assessed by analysis of clinical data from 61 patients who transitioned to nivolumab 480 mg Q4W from 3 mg/kg Q2W during four phase III clinical trials. Results: Compared with 3 mg/kg Q2W, nivolumab 480 mg Q4W produced similar time-averaged concentration, approximately 16% lower trough concentration, and 45% higher peak concentration at steady state. The peak concentration for 480 mg Q4W was significantly lower than that of 10 mg/kg Q2W, a dose previously shown to have an acceptable tolerability and safety profile. Treatment-related adverse events (TRAEs) that started after transitioning from 3 mg/kg Q2W to 480 mg Q4W were reported in 14.8% of patients, with 1.6% of patients reporting grades 3-4 TRAEs. Pooled safety data for these patients are consistent with those for the 3 mg/kg Q2W schedules, and no new safety signals were identified. Conclusions: The time-averaged steady-state exposure and safety profile of nivolumab 480 mg Q4W are consistent with that of 3 mg/kg Q2W across multiple tumor types. Nivolumab 480 mg Q4W represents a new dosing schedule option, and in addition to 240 mg Q2W, provides convenience and flexibility for patient care. Clinical trial numbers: NCT01721772, NCT01668784, NCT01673867, NCT01642004.

What is the optimal systemic treatment of men with metastatic, hormone-naive prostate cancer? A STOPCAP systematic review and network meta-analysis.

Background: Our prior Systemic Treatment Options for Cancer of the Prostate systematic reviews showed improved survival for men with metastatic hormone-naive prostate cancer when abiraterone acetate plus prednisolone/prednisone (AAP) or docetaxel (Doc), but not zoledronic acid (ZA), were added to androgen-deprivation therapy (ADT). Trial evidence also suggests a benefit of combining celecoxib (Cel) with ZA and ADT. To establish the optimal treatments, a network meta-analysis (NMA) was carried out based on aggregate data (AD) from all available studies. Methods: Overall survival (OS) and failure-free survival data from completed Systemic Treatment Options for Cancer of the Prostate reviews of Doc, ZA and AAP and from recent trials of ZA and Cel contributed to this comprehensive AD-NMA. The primary outcome was OS. Correlations between treatment comparisons within one multi-arm, multi-stage trial were estimated from control-arm event counts. Network consistency and a common heterogeneity variance were assumed. Results: We identified 10 completed trials which had closed to recruitment, and one trial in which recruitment was ongoing, as eligible for inclusion. Results are based on six trials including 6204 men (97% of men randomised in all completed trials). Network estimates of effects on OS were consistent with reported comparisons with ADT alone for AAP [hazard ration (HR) = 0.61, 95% confidence interval (CI) 0.53-0.71], Doc (HR = 0.77, 95% CI 0.68-0.87), ZA + Cel (HR = 0.78, 95% CI 0.62-0.97), ZA + Doc (HR = 0.79, 95% CI 0.66-0.94), Cel (HR = 0.94 95% CI 0.75-1.17) and ZA (HR = 0.90 95% CI 0.79-1.03). The effect of ZA + Cel is consistent with the additive effects of the individual treatments. Results suggest that AAP has the highest probability of being the most effective treatment both for OS (94% probability) and failure-free survival (100% probability). Doc was the second-best treatment of OS (35% probability). Conclusions: Uniquely, we have included all available results and appropriately accounted for inclusion of multi-arm, multi-stage trials in this AD-NMA. Our results support the use of AAP or Doc with ADT in men with metastatic hormone-naive prostate cancer. AAP appears to be the most effective treatment, but it is not clear to what extent and whether this is due to a true increased benefit with AAP or the variable features of the individual trials. To fully account for patient variability across trials, changes in prognosis or treatment effects over time and the potential impact of treatment on progression, a network meta-analysis based on individual participant data is in development.

Patterns of relapse in poor-prognosis germ-cell tumours in the GETUG 13 trial: Implications for assessment of brain metastases.

BACKGROUND: The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. METHODS: We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain. RESULTS: With a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (n = 19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, n = 58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy. CONCLUSIONS: Brain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2-3 months of chemotherapy.

Q-TWiST analysis of patients with metastatic castrate naive prostate cancer treated by androgen deprivation therapy with or without docetaxel in the randomised phase III GETUG-AFU 15 trial.

BACKGROUND: Early chemotherapy has recently become a new standard of care for patients with metastatic castrate-naive prostate cancer (mCNPC). The survival benefit is evident in patients with high-volume disease, but less clear in those with low-volume disease. Here, we assessed the trade-offs between toxicity and survival using a Quality-adjusted Time Without Symptoms of disease and Toxicity of treatment (Q-TWiST) analysis. PATIENTS AND METHODS: This analysis was performed from the data of the Genito-Urinary Oncology Group (GETUG)-AFU 15 phase III trial evaluating the benefits of docetaxel (D) combined with androgen deprivation therapy (ADT) versus ADT alone in 385 mCNPC patients. Overall survival was partitioned into three periods, namely toxic phase of treatment (TOX), time before progression without toxicity (TWIST), and progression (PROG). These health states were weighted according to patients' utility to determine quality-adjusted survival times. In threshold analyses, utility for TOX and PROG were varied from 0 to 1. RESULTS: A better quality-adjusted survival was found in the ADT + D arm when the utility for PROG and TOX states were ≤0.2 and ≥ 0.8, respectively. When the utility for PROG was 0.4 or more, ADT + D and ADT alone yielded similar quality-adjusted survival. When patients were stratified into high-volume versus low-volume disease, we found a significant Q-TWiST benefit in favour of the ADT + D arm only for high-volume patients when the utility for PROG was less than 0.35, while we found no benefit in low-volume disease patients, whatever the coefficients tested. CONCLUSION: Early docetaxel may provide significant quality-adjusted survival benefits for patients with mCNPC, especially those with high-volume disease, depending on the values assigned to the times spent in the toxicity phase and after PROG. The Q-TWiST methodology is a useful tool for decision-making regarding trade-offs between survival, PROG and toxicity.

RANK/OPG ratio of expression in primary clear-cell renal cell carcinoma is associated with bone metastasis and prognosis in patients treated with anti-VEGFR-TKIs.

BACKGROUND: Bone metastases (BMs) are associated with poor outcome in metastatic clear-cell renal carcinoma (m-ccRCC) treated with anti-vascular endothelial growth factor tyrosine kinase inhibitors (anti-VEGFR-TKIs). We aimed to investigate whether expression in the primary tumour of genes involved in the development of BM is associated with outcome in m-ccRCC patients treated with anti-VEGFR-TKIs. METHODS: Metastatic clear-cell renal cell carcinoma patients with available fresh-frozen tumour and treated with anti-VEGFR-TKIs. Quantitative real-time PCR (qRT-PCR) for receptor activator of NF-kB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), the proto-oncogene SRC and DKK1 (Dickkopf WNT signalling pathway inhibitor-1). Time-to-event analysis by Kaplan-Meier estimates and Cox regression. RESULTS: We included 129 m-ccRCC patients treated between 2005 and 2013. An elevated RANK/OPG ratio was associated with shorter median time to metastasis (HR 0.50 (95% CI 0.29-0.87); P=0.014), shorter time to BM (HR 0.54 (95% CI 0.31-0.97); P=0.037), shorter median overall survival (mOS) since initial diagnosis (HR 2.27 (95% CI 1.44-3.60); P=0.0001), shorter median progression-free survival (HR 0.44 (95% CI 0.28-0.71); P=0.001) and mOS (HR 0.31 (95% CI 0.19-0.52); P<0.0001) on first-line anti-VEGFR-TKIs in the metastatic setting. Higher RANK expression was associated with shorter mOS on first-line anti-VEGFR-TKIs (HR 0.46 (95% CI 0.29-0.73); P=0.001). CONCLUSIONS: RANK/OPG ratio of expression in primary ccRCC is associated with BM and prognosis in patients treated with anti-VEGFR-TKIs. Prospective validation is warranted.

Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project†.

BACKGROUND: In clinical trials, the use of intermediate time-to-event end points (TEEs) is increasingly common, yet their choice and definitions are not standardized. This limits the usefulness for comparing treatment effects between studies. The aim of the DATECAN Kidney project is to clarify and recommend definitions of TEE in renal cell cancer (RCC) through a formal consensus method for end point definitions. MATERIALS AND METHODS: A formal modified Delphi method was used for establishing consensus. From a 2006-2009 literature review, the Steering Committee (SC) selected 9 TEE and 15 events in the nonmetastatic (NM) and metastatic/advanced (MA) RCC disease settings. Events were scored on the range of 1 (totally disagree to include) to 9 (totally agree to include) in the definition of each end point. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent end points and the associated events. RESULTS: Thirty-four experts scored 121 events for 9 end points. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds, respectively. The expert recommend the use of three and two endpoints in NM and MA setting, respectively. In the NM setting: disease-free survival (contralateral RCC, appearance of metastases, local or regional recurrence, death from RCC or protocol treatment), metastasis-free survival (appearance of metastases, regional recurrence, death from RCC); and local-regional-free survival (local or regional recurrence, death from RCC). In the MA setting: kidney cancer-specific survival (death from RCC or protocol treatment) and progression-free survival (death from RCC, local, regional, or metastatic progression). CONCLUSIONS: The consensus method revealed that intermediate end points have not been well defined, because all of the selected end points had at least one event definition for which no consensus was obtained. These clarified definitions of TEE should become standard practice in all RCC clinical trials, thus facilitating reporting and increasing precision in between trial comparisons.

First-line treatment with sunitinib for type 1 and type 2 locally advanced or metastatic papillary renal cell carcinoma: a phase II study (SUPAP) by the French Genitourinary Group (GETUG)†.

BACKGROUND: Papillary renal cell carcinoma (PRCC), type 1 and type 2, represents 10%-15% of renal cell carcinomas (RCC). There is no standard first-line treatment of metastatic PRCC (mPRCC). Anti-angiogenics have shown activity in retrospective studies but no prospective studies in pure papillary histology have been reported, but one with foretinib. PATIENTS AND METHODS: A prospective phase II study evaluated sunitinib in first-line treatment of mPRCC. The primary end point was overall response rate (ORR). Secondary end points were progression-free survival (PFS) and overall survival (OS). RESULTS: Fifteen and 46 patients, respectively, with type 1 and type 2 mPRCC were enrolled. Using the MSKCC scoring system: 12 (20%), 33 (55%) and 9 (15%) patients were, respectively, in the favourable, intermediate or poor risk group and 7 undetermined. Median follow-up is 51.4 months. In type 1, 2 patients 13% [95% confidence interval (CI) 0.1-30.5] had a partial response (PR), 10 had stable disease (SD) with 5 (33%) ≥12 weeks. In type 2, 5 patients 11% (95% CI 1.9-20.3) had a PR, 25 had SD with 10(22%) ≥12 weeks. Median PFS was 6.6 months (95% CI 2.8-14.8) in type 1 and 5.5 months (95% CI 3.8-7.1) in type 2. Median OS was 17.8 (95% CI 5.7-26.1) and 12.4 (95% CI 8.2-14.3) months, respectively, in type 1 and 2. Safety was as expected with sunitinib for metastatic RCC. CONCLUSION: Sunitinib showed activity in treatment of type 1 and 2 mPRCC but lower than in clear-cell mRCC. Both PFS and OS are longer in type I PRCC. Sunitinib represents an acceptable option in first-line treatment of mPRCC.

Long-term survivors after surgical management of metastatic spinal cord compression.

PURPOSE: Metastatic spinal cord compression (MSCC) incidences are increasing. Our objective was to identify predictive factors involved in long-term survival after use of a surgical approach. METHODS: We retrospectively analyzed all patients referred to our institution for MSCC who underwent surgery (N = 138). We identified patients with an overall survival (OS) rate greater than 2 years, compared their characteristics to the remaining patients, and performed recursive partitioning analysis (RPA). RESULTS: Median OS was 7.8 months (95 % confidence interval 4.4-11.2). Thirty-nine patients presented with OS ≥2 years. A comparative analysis found significant differences concerning the delay (first symptom-surgery, p < 0.001), number of systemic (p = 0.001) or bone metastases (p = 0.013), Karnofsky performance status (KPS) (p = 0.006), Frankel (p = 0.025), ASA scores (p < 0.001), weight loss (p = 0.003), hyperalgia (p = 0.002), chemotherapy use (p = 0.034), and primary tumor (p < 0.001). RPA classification identified six prognostic classes based on the ASA score, primary type, KPS, and systemic metastases. CONCLUSION: Long-term metastatic cancer survivor patients are an increasing population with specific characteristics.

[Head to head comparison of two currently used nomograms predicting the risk of side specific extra capsular extension to indicate nerve sparing during radical prostatectomy for treatment of prostate cancer]. / Validation externe des nomogrammes de prédiction de l'extension extra-prostatique spécifiquement au côté pour des patients atteints de cancer de prostate traités par prostatectomie totale.

OBJECTIVE: To perform a head to head comparison of these two nomograms by an external validation combined with an identification of probability cut-offs when to indicate NS. METHODS: The full models of the nomograms of Ohori et al. and Steuber et al. were used to calculate the risk of ECE based on PSA and side specific information on clinical stage, biopsy Gleason score, % positive cores, and % cancer in cores. A dataset of 968 prostate half lobes was used retrospectively for analysis. All patients underwent laparoscopic robot-assisted or open radical prostatectomy for localized prostate cancer. RESULTS: The predictive accuracy of the Ohori nomogram was at 0.80 and for the Steuber Nomogram at 0.78 (comparison P > 0.05). In the calibration plot, the Ohori nomogram showed less departures from ideal predictions than the Steuber nomogram. The best probability cut-off to allow NS for the Ohori nomogram seemed to be ≤ 10%, permitting NS in 59.7% of all cases and being associated with a false negative rate of 10%. The best cut-off for the Steuber nomogram seemed to be ≤ 8%, permitting NS in 44% and associated with a false negative rate 12.5%. CONCLUSIONS: The Ohori et al. and the Steuber et al. nomograms allow highly accurate and comparable predictions of the risk of side specific ECE. LEVEL OF EVIDENCE: 4.

A phase II trial of high-dose chemotherapy (HDCT) supported by hematopoietic stem-cell transplantation (HSCT) in germ-cell tumors (GCTs) patients failing cisplatin-based chemotherapy: the Multicentric TAXIF II study.

BACKGROUND: High-dose chemotherapy (HDCT) is an effective salvage treatment of germ-cell tumors (GCTs) patients. In the first salvage setting, 30%-70% of patients may achieve durable remissions. Even when HDCT is administered as subsequent salvage treatment, up to 20% of patients may still be definitively cured. However, patients with refractory/relapsed disease still have a very poor long-term prognosis, requiring earlier intervention of HDCT. PATIENTS AND METHODS: This phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy. Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy, nonseminomatous GCT in relapse after first or second lines, partial remission after first line, primary mediastinal GCT in first relapse. Patients received two cycles combining Epirubicin and Paclitaxel (Epi-Tax), followed by three consecutive HDCT, one using a Paclitaxel/Thiotepa (Thio-Tax) association and two using the 5-day Ifosfamide-Carboplatin-Etoposide regimen. The main objective was to determine the complete response rate. RESULTS: Forty-five patients were included between September 2004 and December 2007: 44 received the first HDCT cycle, 39 two HDCT cycles, 29 could receive the whole protocol. Sixteen patients did not receive the entire protocol, including eight (17.7%) for toxic side-effects. Two patients (4.4%) died of toxicities, and 17 (37.7%) of disease progression. With a median follow-up time of 26 months (range, 4-51), the final overall response rate was 48.8% (including a complete response rate of 15.5% and a partial response/negative serum markers rate of 26.6%) in an intent-to-treat analysis. The median progression-free survival (PFS) and overall survival (OS) times were 22 months [95% confidence interval (CI) 2-not reached] and 32 months (95% CI 4-49), respectively. The 2-year PFS was a plateau setup at 50% (95% CI 32-67) and the 2-year OS was 66% (95% CI 44-81). CONCLUSION: The TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatin-based chemotherapy. The toxic death rate remained acceptable in the field of HDCT regimens. TRIAL REGISTRATION NUMBER: NCT00231582.