A equipe do MOC selecionou os abstracts de maior impacto da ASCO 2014. Veja abaixo os destaques em Câncer geniturinário:

Câncer de Próstata

• Sensitivity analyses for radiographic progression-free survival (rPFS): Results from the phase 3 PREVAIL trial comparing enzalutamide to placebo
• PROSPER: A phase 3 study of enzalutamide in nonmetastatic (M0) castration-resistant prostate cancer (CRPC) patients
• 1.5-year post-treatment follow-up of radium-223 dichloride (Ra-223) safety in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases from the phase 3 ALSYMPCA study
• A phase I/II study of the investigational drug alisertib in combination with abiraterone and prednisone (AP) for patients with metastatic castration-resistant prostate cancer (mCRPC) progressing on abiraterone
• A randomized phase III, factorial design, of cabazitaxel and pelvic radiotherapy in patients with localized prostate cancer and high-risk features of relapse
• A randomized, open label, multicenter, phase 3, 2-arm study of androgen deprivation with leuprolide (L), ± docetaxel (D) for clinically asymptomatic prostate cancer (PC) subjects with a rising PSA following definitive local therapy: Safety results
• A study of ERG, PTEN, and ki-67 in a phase III trial assessing docetaxel and estramustine in high-risk localized prostate cancer (GETUG 12)
• Docetaxel-estramustine in localized high-risk prostate cancer: Results of the French Genitourinary Tumor Group GETUG 12 phase III trial
• Prevention of symptomatic skeletal events with denosumab administered every 4 weeks versus every 12 weeks: A noninferiority phase III trial (SAKK 96/12, REDUSE)
•  SWOG S1216: A phase III randomized trial comparing androgen deprivation therapy (ADT) plus TAK-700 with ADT plus bicalutamide in patients with newly diagnosed metastatic hormone-sensitive prostate cancer (HSPC) (NCT01809691)
• The site of visceral metastases (mets) to predict overall survival (OS) in castration-resistant prostate cancer (CRPC) patients (pts): A meta-analysis of five phase III trials

Câncer de Rim

• Genotype correlations with blood pressure and efficacy outcomes from the randomized phase III AXIS trial of second-line axitinib versus sorafenib in metastatic renal cell carcinoma
• A pilot, open-label phase II study of sorafenib combined with cisplatin plus gemcitabine for the treatment of patients with advanced renal collecting duct carcinoma

Câncer de Testículo

• Pazopanib in chemoresistant patients with germ cell tumors (GCT): Updated results of the open-label, single-group, phase 2 Pazotest-01 trial
• A single arm, open-label multicenter phase II trial of everolimus in patients with relapsed/refractory germ cell cancer (RADIT)
• Phase 2 trial of bevacizumab (BEV)/high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) for refractory germ-cell tumors (GCT)

Câncer de Bexiga

• Comparative effectiveness of gemcitabine plus cisplatin (GC) versus methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC)
• Long-term results and prognostic factors for survival following adjuvant chemotherapy (AC) for muscle-invasive urothelial bladder cancer (UC): A French retrospective multicenter cohort
• Neoadjuvant dose-dense gemcitabine and cisplatin (DDGC) in patients (pts) with muscle-invasive bladder cancer (MIBC): Final results of a multicenter phase II study
• Pathologic down-staging following standard (SD) MVAC (methotrexate-vinblastine-doxorubicine-cisplatin) or dose-dense MVAC (DD) neoadjuvant chemotherapy (NC) for muscle-invasive urothelial bladder cancer (UC): A retrospective multicenter cohort of the French Genitourinary Tumor Group (GETUG/AFU)
• Trans Tasman Radiation Oncology Group (TROG) 02.03 phase III trial: Concurrent weekly cisplatin and radiation therapy in localized muscle- invasive bladder cancer—Compliance, toxicity, QOL, and overall results

Câncer de próstata

Sensitivity analyses for radiographic progression-free survival (rPFS): Results from the phase 3 PREVAIL trial comparing enzalutamide to placebo

Abstract No: 5054
Author(s): Michael J. Morris, Yohann Loriot, Tomasz M. Beer, et al.
Background: In the PREVAIL trial, enzalutamide (ENZ), an androgen receptor inhibitor, significantly improved overall survival (HR: 071, P<0.0001) and rPFS (HR: 0.19, P<0.0001) compared with placebo in asymptomatic/mildly symptomatic chemotherapy-naive men with mCRPC (Beer, ASCO GUCS 2014, LBA1). Sensitivity analyses (SA) were performed to assess the impact of different sources of progression on the prespecified rPFS analysis. We also analyzed concordance between central and local reviewers. Methods: In this double-blind, placebo-controlled, multinational study (NCT01212991), 1,717 patients were randomized 1:1 to ENZ 160 mg/day (n=872) or placebo (n=845). rPFS was a co-primary endpoint defined as time from randomization to the earliest objective evidence of radiographic progression by central review or death within 169 days of treatment discontinuation. Radiographic progression was defined by PCWG2 guidelines for bone disease or by RECIST 1.1 for soft tissue disease; bone progression was captured using a validated bone scan data capture assay. The primary rPFS analysis was event driven (at least 410 events). Characteristics of representative SA are reported in the Table. Results: Concordance between central and local assessment of progression was 87.6%. Results of the SA were statistically significant in favor of ENZ (see Table). Conclusions: rPFS sensitivity analyses in PREVAIL demonstrated a consistent and robust treatment benefit with ENZ. Central and local assessment showed good concordance using a quantitative definition of radiographic progression and validated bone scan data assay. Clinical trial information: NCT01212991.

*All p values <0.0001.

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PROSPER: A phase 3 study of enzalutamide in nonmetastatic (M0) castration-resistant prostate cancer (CRPC) patients

Abstract No: TPS5094
Author(s): Maha Hussain, Karim Fizazi, Fred Saad, et al.
Background: There is no standard of care for patients with M0 CRPC. In a recent study, patients with a PSA ≥8 ng/mL or PSA doubling time of ≤10 months had a median time to bone metastasis of only 2 years (Smith et al. Lancet 2012; 379: 39–46). Prostate cancer growth is dependent on androgen receptor (AR) signaling. Enzalutamide (formerly MDV3100) is a novel oral AR inhibitor that targets multiple steps in the AR signaling pathway. In two large Phase 3 studies, enzalutamide was shown to prolong overall survival and radiographic progression-free survival in patients with metastatic CRPC. The objective of the PROSPER trial is to evaluate the efficacy and safety of enzalutamide in M0 CRPC patients. Methods: PROSPER is a randomized, double-blind, placebo-controlled, international Phase 3 study (NCT02003924) initiated in December 2013 and involving more than 200 sites globally. Eligibility criteria include: asymptomatic M0 CRPC; PSA doubling time ≤10 months; screening PSA ≥2 ng/mL; and adequate hematologic, hepatic, and renal function. Approximately 1560 patients will have continued androgen deprivation therapy and will be randomized 2:1 to enzalutamide 160 mg/day or placebo. Patients will be stratified by PSA doubling time (<6 vs 6-10 months) and baseline use of bone-targeting agent (yes vs no).The primary endpoint is metastasis-free survival (MFS) based on central independent review of whole-body radionuclide bone scans for bone disease assessment and CT or MRI scans for soft tissue disease assessment. Imaging will be undertaken at screening and every 16 weeks post randomization till radiographic progression. The study has 90% power to detect a target hazard ratio of 0.75 based on a 2-sided log-rank test at an overall significance level of 0.05. Secondary endpoints include: overall survival; time to pain progression; time to opiate use for prostate cancer pain; time to first use of cytotoxic chemotherapy; time to first use of new antineoplastic therapy; time to PSA progression; PSA response; time to functional status deterioration as assessed by the FACT-P global score; and quality of life as assessed by EQ-5D-5L and QLQ-PR25.

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1.5-year post-treatment follow-up of radium-223 dichloride (Ra-223) safety in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases from the phase 3 ALSYMPCA study

Abstract No: 5070
Author(s): Chris Parker, Nicholas J. Vogelzang, A. Oliver Sartor, David Bottomley, Robert E. Coleman, Irene Skjorestad, Mona Wahba, Sten Nilsson
Conclusions: Long-term follow-up of ~1.5 y after last pt’s final inj showed no new safety concerns or secondary malignancies related to Ra-223. Clinical trial information.

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A phase I/II study of the investigational drug alisertib in combination with abiraterone and prednisone (AP) for patients with metastatic castration-resistant prostate cancer (mCRPC) progressing on abiraterone

Abstract No: TPS5107
Author(s): Jianqing Lin, Ashwin Reddy Sama, Jean H. Hoffman-Censits, et al.
The primary endpoint of the phase II expansion is to determine the proportion of patients without disease progression after alisertib is added to AP, using Minimax Simon two-stage design. The study will analyze the effects of alisertib on PSA kinetics; changes in circulating tumor cells (CTCs) and serum neuroendocrine marker (chromogranin A and NSE) levels. CTCs will also be isolated to determine AK amplification. Clinical trial information:

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A randomized phase III, factorial design, of cabazitaxel and pelvic radiotherapy in patients with localized prostate cancer and high-risk features of relapse

Abstract No: TPS5098
Author(s): Karim Fizazi, Muriel Habibian, Agnes Laplanche, et al.
Conclusion: The aim is to evaluate the benefits of neoadjuvant Cbz and pelvic IMRT in HR localized PC. This is a unique opportunity to study this paradigm in a largely powered trial. Clinical trial information.

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A randomized, open label, multicenter, phase 3, 2-arm study of androgen deprivation with leuprolide (L), ± docetaxel (D) for clinically asymptomatic prostate cancer (PC) subjects with a rising PSA following definitive local therapy: Safety results

Abstract No: 5022
Author(s): Michael J. Morris, Martin Edwin Gleave, Andrew J. Armstrong, et al.
Conclusions: ADT for 18 mo ± D for 10 cycles is feasible when given to pre-metastatic castration-sensitive PC pts. As expected, tx in Arm A was concordant with the known D safety profile. Collection of data for analysis of the primary endpoint is ongoing. Clinical trial information.

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A study of ERG, PTEN, and ki-67 in a phase III trial assessing docetaxel and estramustine in high-risk localized prostate cancer (GETUG 12)

Abstract No: 5063
Author(s): Shanna Rajpar, Philippe Vielh, Agnes Laplanche, et al.
Conclusions: Docetaxel-estramustine is associated with an improved PFS in pts treated for a high-risk localized CaP with ERG expression.

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Docetaxel-estramustine in localized high-risk prostate cancer: Results of the French Genitourinary Tumor Group GETUG 12 phase III trial

Abstract No: 5005
Author(s): Karim Fizazi, Agnes Laplanche, Francois Lesaunier, et al
Conclusions: Docetaxel-estramustine is associated with a borderline significant reduction in the risk of relapse or death in high-risk prostate cancer.  

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Prevention of symptomatic skeletal events with denosumab administered every 4 weeks versus every 12 weeks: A noninferiority phase III trial (SAKK 96/12, REDUSE)

Abstract No: TPS5095
Author(s): Arnoud J. Templeton, Lukas Stalder, Juerg Bernhard, et al.
With a non-inferiority margin of 1.2 for the hazard ratio, power 80% and type I error 5%, the total sample size is 1380. Secondary endpoints include safety, time to subsequent on-trial SSE, quality of life, health economic outcomes, and change in bone turnover markers. Patients with breast or prostate cancer with bone metastases and adequate organ function are eligible. This trial is open for international collaboration

 SWOG S1216: A phase III randomized trial comparing androgen deprivation therapy (ADT) plus TAK-700 with ADT plus bicalutamide in patients with newly diagnosed metastatic hormone-sensitive prostate cancer (HSPC) (NCT01809691)

Abstract No: TPS5102
Author(s): Neeraj Agarwal, Catherine M. Tangen, Maha Hussain, et al.
The experimental regimen with TAK-700 would be of interest if median OS were improved by 25% (i.e., median=68 months). With 4.5 years of accrual and 4 more years of follow-up, and assuming a one-sided alpha=0.025 and 90% statistical power, study needs 1486 eligible men to be randomized. Planned correlatives include serum androgens, bone markers, and circulating tumor cells. Current rate of accrual is ~28 men per month with 220 men accrued so far. Support: NIH/NCI CA32102, CA38926, CA31946 and CA21115, and Millennium: The Takeda Oncology Company.

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The site of visceral metastases (mets) to predict overall survival (OS) in castration-resistant prostate cancer (CRPC) patients (pts): A meta-analysis of five phase III trials

Abstract No: 5002
Author(s): Susan Halabi, William Kevin Kelly, Haojin Zhou, et al
Conclusions: As anticipated, CRPC patients with liver mets had the worst OS (12.1 m). While pts with lung mets had better OS (16.5 months) compared to liver mets pts, they had significantly worse survival than pts with non-visceral bone mets (20 months). These data may help in treatment decisions and in the design of future clinical trials in mCRPC pts.

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Câncer de Rim

Genotype correlations with blood pressure and efficacy outcomes from the randomized phase III AXIS trial of second-line axitinib versus sorafenib in metastatic renal cell carcinoma

Abstract No: 4528
Author(s): Bernard J. Escudier, Brian I. Rini, Robert J. Motzer, et al.
Conclusions: No SNP predicted axitinib outcomes, whereas VEGFR2 rs2071559 may have predicted sorafenib efficacy in patients with mRCC. Sensitivity/specificity limitations, however, preclude the use of this SNP for selecting sorafenib in individual patients.

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A pilot, open-label phase II study of sorafenib combined with cisplatin plus gemcitabine for the treatment of patients with advanced renal collecting duct carcinoma

Abstract No: e15554
Author(s): Xi Nan Sheng, Chuan Liang Cui, Zhihong Chi, et al.
Conclusions: Sorafenib combined with cisplatin plus gemcitabine may benefit patients with advanced CDC. More patients will enroll in the next years.

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Câncer de Testículo

Pazopanib in chemoresistant patients with germ cell tumors (GCT): Updated results of the open-label, single-group, phase 2 Pazotest-01 trial

Abstract No: e15529
Author(s): Patrizia Giannatempo, Luigi Mariani, Nicola Nicolai, et al.
Conclusions: The study has already met the PFS requirements(3 progression-free patients at +3 months) to complete the full accrual of 43 patients.The activity of pazopanib was mainly seen as a reduction of STM, as expected. However responses where also seen in patients yielding divergent histologies. Additional considerations on non-conventional response (densitometric and metabolic) assessment will require more cases.

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A single arm, open-label multicenter phase II trial of everolimus in patients with relapsed/refractory germ cell cancer (RADIT)

Abstract No: e15535
Author(s): Martin H Fenner, Annette Dieing, Karin Oechsle, et al.
Conclusions: Efficacy of everolimus in heavily pretreated GCC pts was sufficient to justify continuation of the trial in the second stage. Accrual was concluded in January 2014, and primary and secondary endpoint analyses are ongoing.

Phase 2 trial of bevacizumab (BEV)/high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) for refractory germ-cell tumors (GCT)

Abstract No: 4517
Author(s): Yago Nieto, Shi-Ming Tu, Roy B. Jones, Nizar M. Tannir, et al.
Conclusions: Tandem HDC with BEV/GDMC followed by BEV/ICE showed promising EFS in pts with heavily pretreated and refractory GCT, exceeding the expected results with carboplatin/etoposide and no BEV, and warrants testing in less heavily pretreated pts.

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Câncer de Bexiga

Comparative effectiveness of gemcitabine plus cisplatin (GC) versus methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC)

Abstract No: 4512
Author(s): Matt D. Galsky, Lauren Christine Harshman, Simon J. Crabb, et al.
Data were collected via an electronic data capture platform from 25 international centers. Eligible pts had cT2-4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or MVAC prior to cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients being assigned to MVAC vs. GC given their: age, calculated creatinine clearance (CrCl), number of cycles of chemotherapy, pure versus mixed histology, Eastern Cooperative Oncology Group performance status, year of diagnosis, cT-stage, and gender. These propensity scores were then included in a log binomial model used to estimate an adjusted relative risk comparing the probability of complete pathologic response (pCR) between patients who received MVAC vs. GC. Survival between the two groups was analyzed as an exploratory endpoint. Conclusions: Neoadjuvant GC and MVAC achieved comparable rates of pCR, in this large retrospective cohort, providing additional evidence to support current practice.

pCR adjusted for propensity scores.

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Long-term results and prognostic factors for survival following adjuvant chemotherapy (AC) for muscle-invasive urothelial bladder cancer (UC): A French retrospective multicenter cohort

Abstract No: 4549
Author(s): Damien Pouessel, Aurelie Le Thuaut, Dimitri Vordos, et al.
We retrospectively analyzed survival of 226 consecutive pts treated with RC and AC for UC with muscle-invasion or lymph node (LN) involvement in 6 French academic hospitals between 2000 and 2009. Non-urothelial cases were excluded. Multivariate Cox proportional hazards regression adjusted for center was used to estimate adjusted hazard ratios with 95% confidence interval.. Conclusions: In this large contemporary retrospective study reporting real-life survivals in pts receiving AC after RC with survival results consistent with published data, LND < 50% and ART in LN+ pts predict a more favorable prognosis after AC. Further studies are warranted to reveal the exact impact of ART in this subset of pts.

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Neoadjuvant dose-dense gemcitabine and cisplatin (DDGC) in patients (pts) with muscle-invasive bladder cancer (MIBC): Final results of a multicenter phase II study

Abstract No: 4513
Author(s): Elizabeth R. Plimack, Jean H. Hoffman-Censits, Alexander Kutikov, et al.
Pts with MIBC, cT2-T4a, cN0-N1 with CrCl >=50 were eligible. Pts received 3 cycles of DDGC (gem 1200 mg/m2, cis 70mg/m2) on day 1, with pegfilgrastim 6 mg day 2 or 3, every 2 wks. Pts with CrCl 50-60 could receive cis split over 2 days. RC with lymph node dissection was to be performed 4-8 weeks after the last dose of DDGC. Primary endpoint was pathologic complete response (pT0) rate. Conclusions: DDGC yielded pT0 rates similar to those reported with Accelerated MVAC. However significant vascular toxicity precluding, delaying or increasing the risk of surgery was noted, leading to early study closure. Clinical trial information: NCT01611662.

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Pathologic down-staging following standard (SD) MVAC (methotrexate-vinblastine-doxorubicine-cisplatin) or dose-dense MVAC (DD) neoadjuvant chemotherapy (NC) for muscle-invasive urothelial bladder cancer (UC): A retrospective multicenter cohort of the French Genitourinary Tumor Group (GETUG/AFU)

Abstract No: 4550
Author(s): Damien Pouessel, Sylvie Chevret, Emmanuelle Bompas, et al.
We conducted a retrospective cohort study in 246 pts who received SD or DD for NC before a planned RC for cT2-T4, cN0 or cN+, M0 UC at 16 French centers from 2004 to 2012. The primary outcome was stage ypT0 at RC. Other PDS end points were no residual muscle-invasion (< ypT2), stage < ypT3, and nodal status. Toxicities, disease-free survival (DFS) and overall survival (OS) were also evaluated. Conclusions: The proportion of pts whose primary tumor were downstaged was not different according to the two regimen. Toxicity was confirmed to be higher in SD than in DD. The GETUG/AFU has launched a randomized trial assessing the DD and gemcitabine-cisplatin regimens in the perioperative setting.

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Trans Tasman Radiation Oncology Group (TROG) 02.03 phase III trial: Concurrent weekly cisplatin and radiation therapy in localized muscle- invasive bladder cancer—Compliance, toxicity, QOL, and overall results

Abstract No: 4543
Author(s): Nirdosh Kumar Gogna, Peter O’Brien, Nigel Spry, et al.
Adult patients with localized Stage T2-T4a, bladder cancer of predominant transitional cell carcinoma histology with no contraindications to the use of pelvic radiation therapy or cisplatin chemotherapy were eligible. Othet exclusion criteria included extensive or multifocal carcinoma in situ and a contracted bladder. An initial maximal transurethral resection of the bladder tumour (TURBT) preceded randomisation. The primary outcome was local failure at 3 years. The secondary endpoints included complete response rate at3 months, overall and disease free survival, acute and late toxicity and QoL. The QoL of patients receiving organ preserving treatments for MIBC had not been previously investigated in a randomised Phase III setting. Intitial accrual target was set at 150 patients over 4 years. Slow accrual lead to early closure with Thirty eight patients were being randomised to arm A and 30 patients to arm B. Conclusions: Overall weekly cisplatin and radiation therapy in MIBC are reasonably well tolerated. Treatment however in the short to medium term does affect Qol. Notwithstanding this negative impact, recovery does follow in the longer term. This is yet another study which suggests that chemoradiation does offer the prospect of improving local control and overall survival compared to radiation therapy alone. Clinical trial information: No NCT00330499.

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