Genitourinary (Non-Prostate) Cancers: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner

Following coverage from The ASCO Post, Emily Lemke, DNP, AGPCNP-BC, AOCNP®, of Medical College of Wisconsin Cancer Center, comments on an adjuvant trial of a checkpoint inhibitor for clear cell renal cell carcinoma (RCC), real-world data comparing first-line platinum regimens for patients with metastatic urothelial carcinoma, and combination regimens for RCC.

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Analysis of predictive clinical markers of outcome in patients with metastatic clear-cell renal cell carcinoma (mRCC) treated with tyrosine-kinases inhibitors (TKI) in first line: A C Camargo Cancer Center experience.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.525 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 525-525 ◽

Cited By ~ 1

Author(s):

Camila Nassif Martins Ferreira ◽

José Augusto Rinck ◽

Christiane Silveira Marinho Albuquerque ◽

Tatiana Vieira Costa ◽

Ana Claudia Machado Urvanegia ◽

...

Keyword(s):

Tyrosine Kinases ◽

Progression Free Survival ◽

Cancer Center ◽

Clinical Markers ◽

First Line ◽

Cell Renal Cell Carcinoma ◽

Durable Response ◽

Clinical Biomarkers ◽

Pre Treatment ◽

High Level

525 Background: TKI have improved the prognosis of patients with mRCC, but rarely lead to durable response. Predictive clinical biomarkers have been studied in the last few years, but most are still controversial. Objective: Identify the role of the clinical and laboratorial biomarkers of prognosis and outcome in mRCC. Methods: A retrospective study with mRCC treated with VEGFR-TKi in first line at A C Camargo Cancer Center (Jan-07 to Apr-16). Studied biomarkers: induced hypertension (HTN), acquiried hypothyroidism, proteinuria, and neutrophil to lymphocyte ratio (NLR). Data were analized in relation to progression free survival (PFS), overall survival (OS), and objetive response rate (ORR) stratified by each marker. Results: We included 94 patients (76.6% sunitinib, 21.3% pazopanib, 2.1% sorafenib). Overall, ORR to VEGFR-TKI was 41.1%; clinical benefit rate was 82.1% (43% Stable disease). Median PFS was 11.4 months (mo)(CI 95% 8.7-14.1) and median OS was 32.1 mo(CI 95% 23.4-40.8). HTN was numerically associated with longer PFS (20.1 vs. 8.2 mo) and OS (37.2 vs. 28.2 mo), but not statistically significant. Only high level TSH (>10) was associated with significant longer PFS and OS, p=0.001 and p<0.001, respectively. There was no association between proteinuria and better outcome. Finally, NLR≥3 pre-treatment was independent prognostic factor, and NLR≥3 post treatment (12aweek) predicted poor OS (9.6 vs 33.9 mo). A “NLR conversion” (before ≥3, turn to <3) was associated with longer OS (28.2 vs. 11.6 mo, p=0.0012). Conclusions: TSH elevation is a good biomarker of better outcome in patients in treatment with TKI. NLR is an important inflamatory marker associated with shorter survival and NLR conversion can be an early biomarker of better outcome to mRCC patients in first line.

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Real World First-Line Treatments and Outcomes of Nab-Paclitaxel Plus Gemcitabine, mFOLFIRINOX and GEMOX in Unresectable Pancreatic Cancer from a Chinese Single Institution

Current Oncology ◽

10.3390/curroncol28010023 ◽

2020 ◽

Vol 28 (1) ◽

pp. 209-219

Author(s):

Qi Quan ◽

Yixing Wang ◽

Fenghua Wang ◽

Dongsheng Zhang ◽

Xiuxing Chen ◽

...

Keyword(s):

Pancreatic Cancer ◽

Real World ◽

Objective Response ◽

Chinese Patients ◽

Cancer Center ◽

Unresectable Pancreatic Cancer ◽

Line Treatment ◽

First Line ◽

Real World Data ◽

First Line Treatment

Background: There have not been any head-to-head prospective studies to compare the effects of different chemotherapy regimens as first-line treatments for unresectable pancreatic cancer (UPC). We aimed to compare the effectiveness of nab-paclitaxel plus gemcitabine, mFOLFIRINOX and gemcitabine plus oxaliplatin (GEMOX) as first-line treatments by using real-world data from Chinese patients. Methods: We retrospectively included patients with UPC treated with nab-paclitaxel plus gemcitabine, mFOLFIRINOX or GEMOX as a first-line treatment at Sun Yat-sen University Cancer Center. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed. Results: A total of 117 patients were administered nab-paclitaxel plus gemcitabine (n = 62), mFOLFIRINOX (n = 30) or GEMOX (n = 25) as first-line chemotherapy. The median OS was 11.1, 10.1 and 10.2 months (p = 0.75) in the nab-paclitaxel plus gemcitabine, mFOLFIRINOX and GEMOX, respectively. The ORR was similar among the three groups (24%, 23% and 32%, p = 0.76) and the DCR was higher in the nab-paclitaxel-gemcitabine group (82%) than the other two groups (60% and 64%, p = 0.04). The most common adverse events of grade 3 or 4 were neutropenia (32%, 28% and 5%), peripheral neuropathy (13%, 16% and 0) and fatigue (9%, 16% and 5%). Febrile neutropenia occurred in 2%, 4% and 5% of the patients in the three groups. Conclusion: In the first line treatment of UPC, our results suggest that nab-paclitaxel plus gemcitabine was associated with a higher DCR than mFOLFIRINOX or GEMOX, while all groups demonstrated similar OS, PFS and ORR.

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Analysis of Efficacy and Toxicity Profile of First-Line Sunitinib or Pazopanib in Metastatic Clear Cell Renal Cell Carcinoma in the Brazilian Population

Journal of Global Oncology ◽

10.1200/jgo.18.00073 ◽

2018 ◽

pp. JGO.18.00073

Author(s):

Pedro Isaacsson Velho ◽

Mirella Nardo ◽

Manoel Carlos Leonardi de Azevedo Souza ◽

Renata R.C. Colombo Bonadio ◽

Guilherme Nader Marta ◽

...

Keyword(s):

Public Health ◽

Renal Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cancer Center ◽

Line Treatment ◽

First Line ◽

Cell Renal Cell Carcinoma ◽

Discontinuation Of Treatment ◽

First Line Treatment

Purpose Sunitinib and pazopanib are multitargeted tyrosine kinase inhibitors (TKIs) that act against vascular endothelial growth factor receptors and are standard first-line treatment options for metastatic clear cell renal cell carcinoma (ccRCC). The Brazilian public health system diverges from the randomized clinical trials in the availability of first and subsequent lines of treatment and in clinical and demographic characteristics of patients. Therefore, it is essential to describe the history of advanced ccRCC during and after TKI treatment in this population. Methods We performed a retrospective analysis of patients with advanced ccRCC treated with a first-line TKI (either sunitinib or pazopanib) between February 2009 and March 2017 in a single academic Brazilian cancer center (Instituto do Câncer do Estado de São Paulo). Results Of the 222 patients, 109 were treated with sunitinib and 113 with pazopanib. The median duration of treatment and overall survival (OS) were 6.4 and 15.2 months for sunitinib and 6.7 and 14.2 months for pazopanib, respectively. Discontinuation of treatment occurred secondarily to progressive disease or death in 64.2% of patients using sunitinib and in 54.8% of patients using pazopanib. Adverse events were responsible for discontinuation of treatment in 28.4% of patients in the sunitinib group and in 22.1% in the pazopanib group. According to Memorial Sloan-Kettering Cancer Center risk categories, the OS was 32.9 months, 15.9 months, and 8.1 months for low risk, intermediate risk, and poor risk, respectively (hazard ratio, 1.72; 95% CI, 1.13 to 2.26; P < .001). Conclusion The use of TKI inhibitors as first-line treatment of metastatic RCC is effective and feasible in the Brazilian public health. However, the median OS of our population is considerably lower compared with the prospective trials that evaluated the same drugs.

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Commentary on “Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma: Hoosier Oncology Group GU 04–75.” Hahn NM, Stadler WM, Zon RT, Waterhouse D, Picus J, Nattam S, Johnson CS, Perkins SM, Waddell MJ, Sweeney CJ; Hoosier Oncology Group, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN

Urologic Oncology Seminars and Original Investigations ◽

10.1016/j.urolonc.2011.11.019 ◽

2012 ◽

Vol 30 (2) ◽

pp. 228-229

Author(s):

H. Barton Grossman

Keyword(s):

Urothelial Carcinoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Cancer Center ◽

Oncology Group ◽

Indiana University ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Metastatic Urothelial Carcinoma

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Outcomes of patients with metastatic clear cell renal cell carcinoma treated with second-line VEGFR-TKI after first-line immune checkpoint inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.575 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 575-575 ◽

Cited By ~ 1

Author(s):

Amishi Yogesh Shah ◽

Ritesh Kotecha ◽

Emily Lemke ◽

Anuradha Chandramohan ◽

Joshua Chaim ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Retrospective Study ◽

Risk Score ◽

Immune Checkpoint Inhibitors ◽

Clear Cell ◽

Checkpoint Inhibitors ◽

Cancer Center ◽

Second Line ◽

First Line ◽

Cell Renal Cell Carcinoma

575 Background: Immune checkpoint inhibitors (ICI) are being increasingly utilized in front-line (1L) setting of metastatic clear-cell renal cell carcinoma (mccRCC). Limited data exist on responses and survival on second-line (2L) VEGFR-TKI therapy after 1L ICI therapy. Methods: This is a retrospective study of mccRCC patients treated with 2L VEGFR-TKI after progressive disease (PD) with 1L ICI. Patients were treated at MD Anderson Cancer Center or Memorial Sloan Kettering Cancer Center between December 2015 and February 2018. Objective response was assessed by blinded radiologists’ review using RECIST v1.1. Descriptive statistics and Kaplan-Meier method were utilized. Results: 70 patients were included in the analysis. Median age at mccRCC diagnosis was 59 years old; 8 patients (11%) had IMDC favorable-risk score, 48 (69%) had intermediate-risk score, and 14 (20%) had poor-risk score. As 1L therapy, 12 patients (17%) received anti-PD-(L)1 monotherapy with nivolumab or atezolizumab, 33 (47%) received nivolumab plus ipilimumab, and 25 (36%) received combination anti-PD-(L)1 plus bevacizumab. 2L TKI therapies included pazopanib, sunitinib, axitinib, and cabozantinib. On 2L TKI therapy, one patient (1.5%) achieved a complete remission (CR), 27 patients (39.7%) a partial response (PR), and 36 patients (52.9%) stable disease (SD), adding to a 94% disease control rate (DCR). Median progression-free survival (mPFS) was 13.2 months (95% CI: 10.1, NA). Estimated 1-yr overall survival (OS) probability was 79.6% (95% CI: 70.2 – 90.3). Median duration of 2L TKI therapy was 10.1 months. In total, 45.7% of subjects required a dose reduction, and 27% of patients discontinued treatment due to toxicity. Conclusions: In this retrospective study of patients with mccRCC receiving 2L TKI monotherapy following 1L ICI, we observed 2L antitumor activity and tolerance comparable to historical data for first-line TKI. Further studies are needed to evaluate optimal strategies and sequencing of therapies in mccRCC.

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First Report of Oncological Outcome and Prognostic Analysis in a First-Line Setting of Short Hydration Gemcitabine and Cisplatin Chemotherapy for Patients with Metastatic Urothelial Carcinoma

Oncology ◽

10.1159/000517326 ◽

2021 ◽

pp. 1-10

Author(s):

Taku Naiki ◽

Takashi Nagai ◽

Yosuke Sugiyama ◽

Toshiki Etani ◽

Satoshi Nozaki ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Risk Index ◽

Objective Response ◽

Oncological Outcome ◽

Nutritional Risk ◽

First Line ◽

Prognostic Analysis ◽

Nutritional Risk Index ◽

Metastatic Urothelial Carcinoma ◽

Gemcitabine And Cisplatin

Objectives: The aim of the study was to examine the effectiveness of a modified-short hydration gemcitabine and cisplatin (m-shGC) regimen for patients with metastatic urothelial carcinoma (mUC) and to assess the efficacy of a geriatric nutritional risk index (GNRI) with regard to prognosis. Patients and Methods: From January 2016 to July 2020, 68 patients with mUC underwent first-line m-shGC therapy with 70 mg/m2 cisplatin and 1,000 mg/m2 gemcitabine (days 1, 8, and 15), with 2,050 mL fluid replaced on the first day of each 28-day cycle. Prior to the start of treatment, the serum neutrophil-to-lymphocyte ratio (NLR), and levels of albumin and C-reactive protein (CRP) in serum, as well as body heights and weights were measured. Patients were grouped according to GNRI <92 (low) or ≥92 (high). The analysis of data was done retrospectively. Results: Median follow-up was found to be 12.9 (range 1.7–50.2) months and the objective response rate (ORR) was 54.4% after m-shGC treatment. The ORR was significantly different when high and low-GNRI groups were compared (ORR: 28.0 vs. 69.8% in low- vs. high-GNRI groups). Median overall survival (OS) was calculated as 8.6 (95% confidence interval [CI]: 5.4–21.3) and 34.5 (95% CI: 20.5–NA) months for low- and high-GNRI groups, respectively (p < 0.0001). Unlike for NLR and CRP, univariate and multivariate analyses revealed that low GNRI and visceral metastases were significant prognostic factors for short OS. Conclusions: First-line m-shGC showed a survival benefit for mUC, with GNRI a useful prognostic biomarker.

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Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel towards Prostate Cancer Relapse

Genes ◽

10.3390/genes12020257 ◽

2021 ◽

Vol 12 (2) ◽

pp. 257

Author(s):

Yan Gu ◽

Mathilda Jing Chow ◽

Anil Kapoor ◽

Xiaozeng Lin ◽

Wenjuan Mei ◽

...

Keyword(s):

Prostate Cancer ◽

Differential Expression ◽

Cancer Progression ◽

Lncap Cell ◽

Endocrine Resistance ◽

Gene Panel ◽

The Cancer Genome Atlas ◽

Cancer Center ◽

Poor Overall Survival ◽

Cell Renal Cell Carcinoma

Contactin 1 (CNTN1) is a new oncogenic protein of prostate cancer (PC); its impact on PC remains incompletely understood. We observed CNTN1 upregulation in LNCaP cell-derived castration-resistant PCs (CRPC) and CNTN1-mediated enhancement of LNCaP cell proliferation. CNTN1 overexpression in LNCaP cells resulted in enrichment of the CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_3 gene set that facilitates endocrine resistance in breast cancer. The leading-edge (LE) genes (n = 10) of this enrichment consist of four genes with limited knowledge on PC and six genes novel to PC. These LE genes display differential expression during PC initiation, metastatic progression, and CRPC development, and they predict PC relapse following curative therapies at hazard ratio (HR) 2.72, 95% confidence interval (CI) 1.96–3.77, and p = 1.77 × 10−9 in The Cancer Genome Atlas (TCGA) PanCancer cohort (n = 492) and HR 2.72, 95% CI 1.84–4.01, and p = 4.99 × 10−7 in Memorial Sloan Kettering Cancer Center (MSKCC) cohort (n = 140). The LE gene panel classifies high-, moderate-, and low-risk of PC relapse in both cohorts. Additionally, the gene panel robustly predicts poor overall survival in clear cell renal cell carcinoma (ccRCC, p = 1.13 × 10−11), consistent with ccRCC and PC both being urogenital cancers. Collectively, we report multiple CNTN1-related genes relevant to PC and their biomarker values in predicting PC relapse.

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