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Introduction
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February 2015 - present
March 2013 - present
July 2013 - present
Publications
Publications (131)
What is this summary about?:
This summary describes the results from the TALAPRO-2 research study (also known as a clinical trial). The TALAPRO-2 study tested the combination of two medicines called talazoparib plus enzalutamide. This combination of medicines was used as the first treatment for adult patients with metastatic castration-resistant p...
5009
Background: Over the last six decades, platinum-based chemotherapy has been the standard of care first-line treatment for advanced penile squamous cell carcinoma (PSCC). Advanced PSCC has poor prognosis with limited treatment options. Immune checkpoint inhibitors (ICI) have been associated with improved efficacy in different types of malignanc...
Background
Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy.
Patients and Methods
Medical records of patients with documented m...
Purpose
Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperati...
109
Background: Cohort 2 of the TALAPRO-2 (NCT03395197) study demonstrated benefit in radiographic progression-free survival (rPFS) with talazoparib (TALA) plus enzalutamide (ENZA) (n=200) vs placebo (PBO) + ENZA (n=199) across gene subgroups in men with HRRm receiving first-line treatment for mCRPC. Post-hoc analyses aimed to understand PROs by HR...
10
Background: Penile carcinoma is a rare malignancy. However, in developing countries the incidence rate is higher with approximately 6 cases per thousand men. mPC has a very poor prognosis and effective systemic treatments are an unmet need. Understanding the molecular alterations is essential for evaluating possible targets for more effective sy...
116
Background: In TALAPRO-2 (NCT03395197), TALA +ENZA vs PBO + ENZA demonstrated significant improvement in radiographic progression-free survival, a manageable adverse event (AE) profile, and a delay in time to definitive clinical meaningful deterioration in global health status (GHS)/quality of life (QoL) overall and across all pre-specified sub...
178
Background: TALAPRO-2 demonstrated statistically significant improvement in radiographic PFS with 1L talazoparib (TALA) + enzalutamide (ENZA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without HRR gene alterations (HRRm). Tumors were prospectively determined to harbor HRRm. Pts were randomized 1:1 to...
136
Background: Prior to randomization in TP-2, patients (pts) (N=805; all-comers) were prospectively assessed for HRR gene alterations in tumor tissue and/or ctDNA using FoundationOne CDx and/or FoundationOne Liquid CDx. In the all-comers cohort, talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment for pts with mCRPC significantly impr...
Preclinical evidence has suggested an interplay between the androgen receptor, which largely drives the growth of prostate cancer cells, and poly(ADP-ribose) polymerase. This association provides a rationale for their co-inhibition for the treatment of metastatic castration-resistant prostate cancer (mCRPC), an area of unmet medical need. The phase...
Background
Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pemb...
5053
Background: The phase 3 TALAPRO-2 study demonstrated a clinically meaningful and statistically significant improvement in radiographic progression-free survival for 1st-line TALA + ENZA versus PBO + ENZA in men with mCRPC, unselected for homologous recombination repair gene alterations (all-comers population). Here, we detail the safety profil...
5013
Background: TALAPRO-2 (NCT03395197) showed statistically significant improvement in radiographic progression free survival with TALA + ENZA (n=402) vs PBO + ENZA (n=403) (HR=0.63 95% CI 0.51-0.78; P<0.001) in men receiving 1L treatment for mCRPC. Here we report PRO endpoints from TALAPRO-2. Methods: PROs were assessed at day 1 (baseline) and a...
Background:
Co-inhibition of poly(ADP-ribose) polymerase (PARP) and androgen receptor activity might result in antitumour efficacy irrespective of alterations in DNA damage repair genes involved in homologous recombination repair (HRR). We aimed to compare the efficacy and safety of talazoparib (a PARP inhibitor) plus enzalutamide (an androgen rec...
5056
Background: In TALAPRO-2 (NCT03395197), pts unselected for tumor genetic alterations in DNA damage repair pathways, directly or indirectly involved with HRR, received TALA + ENZA (n=402) or PBO + ENZA (n=403) as 1L treatment for mCRPC. HRR status was informed by tumor tissue for 804 pts (99.9%), by tumor tissue and ctDNA for 114 (14.2%), and b...
5004
Background: TALAPRO-2 is the first phase 3 study to combine the poly(ADP-ribose) polymerase inhibitor TALA with the androgen receptor inhibitor ENZA in pts with 1L mCRPC unselected (Cohort 1—previously reported) or selected (Cohort 2) for HRR gene alterations. Here, we report results of the prespecified, independently powered analysis of pts w...
LBA17
Background: TALAPRO-2 (NCT03395197) is the first phase 3 study to combine the poly(ADP-ribose) polymerase inhibitor TALA with the androgen receptor inhibitor ENZA. Pts unselected for genetic alterations in DNA damage repair pathways, directly or indirectly involved with homologous recombination repair (HRR), received either TALA + ENZA or PBO...
TPS14
Background: Penile squamous cell carcinoma (PSCC) is an uncommon malignancy which accounts for 2,300 new cases and 400 deaths annually worldwide. However, in low-income countries from South America, Asia and Africa, incidence corresponds to 10-20% of all malignancies in men. Approximately 4% of PSCC patients present with metastatic disease at...
TPS272
Background: Treatment of metastatic castration-resistant prostate cancer (mCRPC) has been steadily evolving during the last decade, but access remains a significant issue in low- and middle-income countries (LMICs). As novel therapies emerge and translate into clinical practice, the gap in treatment patterns between patients who do or do not...
Purpose
Germ-cell tumors (GCTs) are the most common malignancy in young men. There is a paucity of data on GCTs in developing countries. LACOG 0515 study aimed to evaluate clinical characteristics and treatment outcomes in patients with GCTs from Brazilian cancer centers.
Methods
This is a retrospective cohort study evaluating male patients diagno...
Many genetic variants affect disease risk by altering context-dependent gene regulation. Such variants are difficult to study mechanistically using current methods that link genetic variation to steady-state gene expression levels, such as expression quantitative trait loci (eQTLs). To address this challenge, we developed the cistrome-wide associat...
What is this summary about?
This summary describes the design of an ongoing research study (also known as a clinical trial) called TALAPRO-2. The TALAPRO-2 trial is testing the combination of two medicines called talazoparib and enzalutamide as a first treatment in adult men with metastatic castration-resistant prostate cancer. The study began in D...
BACKGROUND
Immune checkpoint inhibitors (ICI) have shown clinical benefit among patients with advanced kidney cancer. Their cost burden hardens its access, especially in low- and middle-income countries. To set solutions, the impact of geographical and socioeconomic differences in the clinical outcomes and survival of renal cell carcinoma (RCC) pat...
e16549
Background: Treatment of Urothelial Cancer (UC) is rapidly evolving with innovative biomarker-based approaches. Alterations in the gene encoding fibroblast growth factor receptor (FGFR) are frequent in UC and are an emerging focus for targeted therapy. However, real-world data on FGFR prevalence, as well as clinicopathological characteristic...
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), apalu...
PARP inhibitors in combination with androgen receptor-targeted therapy have demonstrated potential in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Here, we describe the design and rationale of the multinational, Phase III, two-part TALAPRO-2 study comparing talazoparib plus enzalutamide versus placebo plus enzalutamide...
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-compara...
TPS5089
Background: TALA blocks poly(ADP-ribose) polymerase (PARP) activity and traps PARP on single-strand DNA breaks, preventing DNA damage repair (DDR) and causing death of cells with DDR alterations (eg, BRCA1/2). a TALA is approved in multiple countries as monotherapy for germline BRCA1/2-mutated human epidermal growth factor receptor 2 (HER2)...
TPS178
Background: In metastatic hormone-sensitive prostate cancer (mHSPC), abiraterone combined with androgen deprivation therapy (ADT) is highly effective in improving patient outcomes. However, around 20% of patients progress to castration-resistant disease within 12 months of treatment; these patients have shorter survival and limited treatment...
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 achi...
TPS497
Background: There is lack of high-quality and comprehensive data on advanced urothelial cancer in Latin America. Pathological and clinical outcomes information of this cancer can help the scientific community to understand the current standard of treatment and identify possible gaps for optimal care. Very few translational studies were perfo...
INTRODUCTIONPatients diagnosed with breast cancer (BC) in Brazil are on average 54 years old and the majority (70%) have stage II-III. Age and clinical stage have a negative impact on patient personal life and labor productivity. The socioeconomic status is a fundamental part of the population’s health, which includes marital and employment status....
Background:
Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carc...
Purpose
According to pathologico-clinical features, patients diagnosed with localized prostate cancer (PCa) are stratified into distinct risk groups (low-, intermediate- or high-risk). Data has demonstrated that ⁶⁸Ga-PSMA PET/CT is superior to conventional radiological exams (CT or MRI and bone scintigraphy) in the primary staging of high-risk loca...
![Levels of recommendation. [Adapted from CEBM (2019)]](publication/341393175/figure/tbl1/AS:891272113954816@1589507239087/Levels-of-recommendation-Adapted-from-CEBM-2019_Q320.jpg)
PurposeThe outcome of RCC has improved considerably in the last few years, and the treatment options have increased. LACOG-GU and LARCG held a consensus meeting to develop guidelines to support the clinical decisions of physicians and other health professionals involved in the care of RCC patients.Methods
Eighty questions addressing relevant advanc...
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...
TPS5598
Background: TALA blocks poly(ADP-ribose) polymerase (PARP) activity and traps PARP on single-strand DNA breaks, preventing DNA damage repair (DDR) and causing death of cells with DDR alterations (eg BRCA1/2). a TALA has been approved in multiple countries as monotherapy for germline BRCA1/2-mutated human epidermal growth factor receptor 2-n...
Introduction
Combination treatments with immuno-oncology agents (IO) and IO plus vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) have been approved for first line treatment of patients with mRCC. No direct comparisons have been performed among these treatment options. We have performed a systematic review and netwo...
TPS264
Background: TALA is a poly(ADP-ribose) polymerase (PARP) inhibitor that inhibits PARP1/2 and traps PARP on DNA, preventing DNA damage repair (DDR) and causing death of cells with DDR mutations (eg BRCA1/2). TALA is approved in multiple countries for germline BRCA1/2-mutated HER2- advanced breast cancer. ENZA is an established therapy for CRP...
We previously showed that alterations in mTOR pathway genes were correlated with response to rapalog therapy in metastatic renal cell carcinoma (mRCC), when the analysis focused on extremes of response. Herein, we expand on the prior cohort and examine genetic correlations with rapalog response in a dataset not selected for extremes of response. Tu...
Background
Renal cell cancer (RCC) is one of the 10 most common cancers in the world, and its incidence is increasing, whereas mortality is declining only in developed countries. Therefore, two collaborative groups, The Latin American Oncology Cooperative Group-Genitourinary Section (LACOG-GU) and the Latin American Renal Cancer Group (LARCG), held...
Determining the function of non-coding regulatory variants in cancer remains a key challenge. We investigated genetic (germline and somatic) determinants of regulatory mechanisms in renal cell carcinoma (RCC) using H3K27ac ChIP-seq data in 10 matched tumor/normal samples and RNA-seq data from 496/66 tumor/normal samples from The Cancer Genome Atlas...
Determining the function of non-coding regulatory variants in cancer remains a key challenge. We investigated genetic (germline and somatic) determinants of regulatory mechanisms in renal cell carcinoma (RCC) using H3K27ac ChIP-seq data in 10 matched tumor/normal samples and RNA-seq data from 496/66 tumor/normal samples from The Cancer Genome Atlas...
4579
Background: Although surgery is the cornerstone in the treatment of most cases of localized kidney cancer, up to 30% of patients will experience disease recurrence at three years of follow-up. Three RCTs with VEGFR TKIs (ASSURE, PROTECT and ATLAS) failed to demonstrate improvement in disease-free survival (DFS). Only S-TRAC trial showed a sign...
Determining the function of non-coding regulatory variants in cancer is a key challenge transcriptional biology. We investigated genetic (germline and somatic) determinants of regulatory mechanisms in renal cell carcinoma (RCC) using H3K27ac ChIP-seq data in 10 matched tumor/normal samples and RNA-seq data from 496/66 tumor/normal samples from The...
Purpose:
Health determinants vary according to geographic region and may affect the outcomes of patients with metastatic renal cell carcinoma (mRCC) treated during clinical trials of targeted therapy. Here, we investigate the overall survival (OS) of patients with mRCC treated in the era of targeted therapy by geographic region.
Methods:
We cond...
The incidence of kidney cancer is rising. Due to the widespread use of abdominal imaging for unrelated indications, small renal masses have been increasingly detected incidentally. A better understanding of the biology underlying the different tumor types arising from the kidney cortex has opened new avenues to define diagnosis, prognosis, and trea...
Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have shown activity in metastatic clear cell renal cell carcinoma (ccRCC). Data on the activity of these agents in patients with non-clear cell RCC (nccRCC) or patients with sarcomatoid/rhabdoid differentiation is limited. In this multicenter analysis, we explored the efficacy of PD-1/PD-...
The incidence of kidney cancer is rising. Due to the widespread use of abdominal imaging for unrelated indications, small renal masses have been increasingly detected incidentally. A better understanding of the biology underlying the different tumor types arising from the kidney cortex has opened new avenues to define diagnosis, prognosis, and trea...
Background
The predictive role of excision repair cross-complementing group 1 (ERCC1) as a predictive factor in patients with advanced urothelial cancer (AUC) treated with platinum-based treatment is not well defined. Here, we evaluate the role of ERCC1 in patients with AUC treated with platinum-based treatment.
Methods
We performed comprehensive,...
Introduction:
Gene-expression signatures for prognosis have been reported in localized renal cell carcinoma (RCC). The aim of this study was to test the predictive power of two different signatures, ClearCode34, a 34-gene signature model [Eur Urol 2014;66:77-84], and an 8-gene signature model [Eur Urol 2015;67:17-20], in the setting of systemic th...
482
Background: PD1/PDL1 inhibitors have shown significant activity in the treatment of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC), but their activity in nccRCC is poorly characterized. Methods: We conducted a retrospective multicenter study of pts with metastatic nccRCC treated with PD1/PDL1 inhibitors. Baseline clinica...
Purpose:
Obesity is an established risk factor for clear cell renal cell carcinoma (RCC); however, some reports suggest that RCC developing in obese patients may be more indolent. We investigated the clinical and biologic effect of body mass index (BMI) on treatment outcomes in patients with metastatic RCC.
Methods:
The impact of BMI (high BMI:...
Advances in next-generation sequencing have provided a unique opportunity to understand the biology of disease and mechanisms of sensitivity or resistance to specific agents. Renal cell carcinoma (RCC) is a heterogeneous disease and highly variable clinical responses have been observed with vascular endothelial growth factor (VEGF)-targeted therapy...
Background:
Tumour expression of selected microRNAs (miRs) correlates with cisplatin efficacy in multiple cancers. We investigated the role of selected miRs in patients receiving cisplatin-based therapy for advanced urothelial carcinoma (UC).
Methods:
RNA was extracted from formalin-fixed paraffin-embedded tumour from 83 advanced UC patients who...
Background:
Targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) may be associated with a high rate of toxicity that undermines treatment efficacy and patient quality of life. Polymorphisms in genes involved in the pharmacokinetic pathways of TTs may predict toxicity.
Objective:
To investigate whether selected single-nucleotide polymo...
Background:
Neutrophil-to-lymphocyte ratio (NLR), if elevated, is associated with worse outcomes in several malignancies.
Objective:
Investigation of NLR at baseline and during therapy for metastatic renal cell carcinoma.
Design, setting, and participants:
Retrospective analysis of 1199 patients from the International Metastatic Renal Cell Car...
Immunotherapy has become an important component of modern oncology therapy. Recently
methods of immune checkpoint blockade include; anti-CTLA-4, anti-PD-1/PD-L1, or a combination
of both therapies and have been developed with the objective of restoring immune system
T-cell responses against cancer. This strategy has demonstrated important clinical...
Purpose:
We examined the hypothesis that mutations in mTOR pathway genes are associated with response to rapalogs in metastatic renal cell carcinoma (mRCC).
Experimental design:
We studied a cohort of mRCC patients who were treated with mTOR inhibitors with distinct clinical outcomes. Tumor DNA from 79 subjects was successfully analyzed for muta...
Background:
Inhibiting VEGF and mammalian target of rapamycin (mTOR) pathways are standard treatment approaches for patients with metastatic renal cell carcinoma (mRCC). Here we report the activity and safety of the VEGF ligand inhibitor bevacizumab and the mTOR inhibitor temsirolimus combination in patients with clear cell (CC) and non-clear cell...
616
Background: Polybromo-1 (PBRM1) and BRCA1 associated protein-1 (BAP1) are genes commonly mutated in clear cell RCC (ccRCC) and have been associated with clinical outcome. This work aims to evaluate the impact of PBRM1 and BAP1 expression by IHC in mRCC patients treated with VEGF-TT. Methods: PBRM1 and BAP1 expression was evaluated by IHC in a T...
73
Background: Abiraterone and enzalutamide are currently approved for mCRPC patients. Both drugs have distinct mechanisms of action and may have different toxicity profile. There are limited data comparing the side effects of abiraterone and enzalutamide. We performed a meta-analysis of randomized controlled trials (RCT) to better characterize the...
Background: Abiraterone and enzalutamide are currently approved for mCRPC patients. Both drugs have distinct mechanisms of action and may have different toxicity profile. There are limited data comparing the side effects of abiraterone and enzalutamide. We performed a meta-analysis of randomized controlled trials (RCT) to better characterize the ri...