Earlier Surrogate for Survival After RP Relapse Possibly ID’d

Avelumab Ups Survival in Advanced UC

Study shows benefit of adding the drug to best supportive care as part of first-line maintenance therapy

BY JODY A. CHARNOW FIRST-LINE maintenance therapy with avelumab plus best supportive care (BSC) significantly prolongs overall survival (OS) compared with BSC alone among patients with unresectable locally advanced or metastatic urothelial carcinoma (UC) who had disease that did not progress while on first-line chemotherapy, according to study findings presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 and published concurrently in the New England Journal of Medicine.

In the phase 3 JAVELIN Bladder 100 trial in which investigators randomly assigned 700 patients to receive avelumab, an immunotherapeutic drug, plus BSC or BSC alone, OS at 1 year was 71.3% in the avelumab group compared with 58.4% in the BSC-only arm, study investigator Petros Grivas, MD, PhD, of the University of Washington (UW) in Seattle, reported in a video

SU vs NU for Ureteral Tumors

BY JODY A. CHARNOW SEGMENTAL ureterectomy (SU) may be an appropriate alternative to radical nephroureterectomy (NU) for the treatment of high-risk ureteral tumors.

A retrospective analysis using data from 2006 to 2013 from the National Cancer Database (NCDB) revealed no significant difference in overall survival (OS) between patients treated with SU or NU after adjusting for multiple variables, Patrick M. Lec, MD, of the David Geffen School of Medicine at the University of California, Los Angeles, and colleagues reported in Urologic Oncology.

The study included 1962 patients with clinically localized high-risk ureteral tumors. Selection criteria aimed to approximate the European Association of Urology (EAU) definition of highrisk upper tract urothelial carcinoma (UTUC) within the limits of the NCDB, the researchers explained.

Of the 1962 patients included, 1421 (72.4%) underwent radical NU and 541 (27.6%) underwent SU. Lymphadenectomy was performed in only Survival Rates at 1 Year

First-line maintenance therapy with avelumab plus best supportive care (BSC) vs BSC alone significantly increased 1-year overall survival (OS) rates among patients with unresectable locally advanced or metastatic urothelial carcinoma whose disease had not progressed while on first-line chemotherapy, including a subset of patients with PD-L1-positive disease.

80

60

40

71.3% 79.1%

■ Entire cohort

58.4%

■ PD-L1-positive patients

60.4%

20

0

Avelumab + BSC BSC alone

1-Year Survival Rates

Source: Grivas P, Park SH, Voog E, et al. Avelumab first-line (1L) maintenance + best supportive care (BSC) vs BSC alone with 1L chemotherapy (CTx) for advanced urothelial carcinoma (UC): Subgroup analyses from JAVELIN Bladder 100. Presented at: ESMO Virtual Congress 2020. Abstract 704MO

presentation. Median OS was 21.4 (24.8%) received adjuvant chemother-

Dr Lec and colleagues stated that their study had limitations that derive from shortcomings of data extraction multifocality and hydronephrosis “that fall within the EAU definition of highdisease biology that favor performance of radical extirpative surgery.” ■ months in the avelumab group compared with 14.3 months in the control group. Avelumab treatment was significantly associated with a 31% decreased risk of death, according to Dr Grivas, associate professor of oncology at UW and director of UW Medicine’s Genitourinary Cancers Program.

In addition, avelumab significantly prolonged OS among PD-L1–positive patients. OS at 1 year was 79.1% in the avelumab group and 60.4% in the control group. Avelumab was significantly associated with a 44% decreased risk of death.

The median progression-free survival (PFS) was 3.7 months in the avelumab group and 2.0 months in the control group in the study population as a whole and 5.7 months and 2.1 months, respectively, in the PD-L1-positive population.

Avelumab was significantly associated with a 38% and 44% decreased risk for disease progression or death in the study population as a whole and the PD-L1-positive population, respectively, according to the investigators.

The incidence of adverse events (AEs) from any cause was 98.0% in the avelumab group and 77.7% in the control arm, the study found. The incidence of grade 3 or higher AEs was 47.4% and 25.2%, respectively.

The study was sponsored by Pfizer, and is part of an alliance between Pfizer and

446 patients (22.7%). Among the 1092 patients with advanced pathology, 271 apy. The median follow-up time was 33.2 months for the radical NU group and 31.6 months for the SU group.

In the NU group, lymphadenectomy was associated with a 42% decreased risk of death when more than 3 nodes were removed, the authors reported. Receipt of adjuvant chemotherapy for advanced pathology had no effect on OS in either treatment group.

“This retrospective cohort study supports the performance of lymphadenectomy and SU in patients with high-risk ureteral tumors,” the authors concluded.

methods in the NCDB. Although they were able to restrict their analysis to ureteral tumors, they were not able to discriminate between tumor locations along the ureter or other factors such as risk UTUC,” the investigators wrote. “This invites some degree of selection bias, as some of these features technically dictate NU (i.e., proximal location) and others reflect more aggressive Merck KGaA, Darmstadt, Germany. ■

Earlier Surrogate for Survival After RP Relapse Possibly ID’d

CASTRATION-RESISTANT prostate cancer (CRPC)-free survival among men with biochemical failure following radical prostatectomy (RP) is closely correlated with metastasis-free survival (MFS), suggesting the former could be an intermediate endpoint in clinical trials, researchers concluded in a poster presentation during the European Society for Medical Oncology Virtual Congress 2020.

MFS is a surrogate for overall survival in men with localized prostate cancer, but this endpoint may take years to develop in patients with nonmetastatic castration-sensitive disease, a team co-led by Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, and Durham VA Medical Center in Durham, North Carolina, and Zachary Klaassen, MD, of Augusta University in Augusta, Georgia, explained. “Other evidence-based intermediates that occur earlier in the disease course are needed for clinical trial design to expedite evaluating new therapies,” they noted.

Drs Freedland and Klaassen and their colleagues conducted a retrospective cohort study that included 210 men who had biochemically recurrent PCa after RP, a PSA doubling time of less than 9 months, and no evidence of metastasis at the time of starting androgen deprivation therapy (ADT). The primary outcome was the correlation between CRPC-free survival (CRPC-FS) and MFS.

During a median follow-up of 79.4 months after initiation of ADT, CRPC or death occurred in 131 patients and metastasis developed in 132 patients. The median CRPC-FS and MFS was 100 months and 104 months, respectively. When limited to men with a PSA at ADT initiation greater than 1 ng/mL and those with a Charlson Comorbidity Index of 2 or less, there was an approximately 85% and 88% correlation between CRPC-FS and MFS, respectively, and 76% and 74% correlation between time to CRPC and time to metastasis, respectively. ■

Alpha Blockers Up CKD Progression Risk

Use of these agents increases the likelihood of a 30% or greater eGFR decline, recent study shows

BY JOHN SCHIESZER ALPHA BLOCKER USE to control hypertension may be associated with a higher risk for kidney disease progression but a lower risk for cardiac events and mortality compared with use of alternative antihypertensive medications in patients with chronic kidney disease (CKD), according to a recent populationbased retrospective study published in the American Journal of Kidney Diseases.

Nuanced Discussions With Patients The findings could allow clinicians to have more nuanced discussions with patients who have CKD regarding the long-term risks associated with alpha blocker use, lead investigator Gregory L. Hundemer, MD, of the Ottawa Hospital Research Institute and The Ottawa Hospital, Riverside Campus, Ontario, Canada, told Renal & Urology News. “Nephrologists need to balance the pros and cons of prescribing alpha blockers to their patients on a case-bycase basis,” Dr Hundemer said.

Out of 381,120 patients aged 66 years or older living in Ontario who received treatment for hypertension from 2007 to 2015, the investigators identified 16,088 patients who were newly prescribed alpha blockers (doxazosin, terazosin, and prazosin) and matched them with 16,088 patients who were newly prescribed antihypertensive medications other than alpha blockers (ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, beta blockers, and thiazide diuretics). Patients had a mean age of 76 years and mean estimated glomerular filtration rate (eGFR) of 62 mL/min/1.73m2 .

The investigators looked at the following outcomes: a 30% or larger decline in estimated glomerular filtration rate (eGFR), dialysis initiation or kidney transplantation, composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation, safety (hypotension, syncope, falls, fractures) events, and mortality. The study excluded patients with prior cardiac events. Dr Hundemer and colleagues

Study finds a 28% greater likelihood of requiring renal replacement therapy.

examined outcomes according to category of eGFR (in mL/min/1.73 m2): 90 or higher, 60-89, 30-59, and less than 30.

Alpha blocker use was significantly associated with a 14% higher risk of a 30% or greater eGFR decline and 28% increased likelihood of dialysis initiation or kidney transplantation compared with use of medications other

RCC Surgery Delay Safe, Study Finds

DELAYING SURGERY for clinically localized renal cell carcinoma (RCC) of up to 6 months does not increase the risk of tumor progression, a finding that has implications for RCC treatment during the COVID-19 pandemic, according to findings presented at the 2020 International Kidney Cancer Symposium and published in Urologic Oncology.

In a study of 29,746 patients who underwent partial or radical nephrectomy for cT1b, cT2a, or cT2b RCC tumors, who were identified using the National Cancer Database, a team led by Eric A. Singer, MD, of the Rutgers Cancer Institute of New Jersey in New Brunswick, found that delaying surgery for more than 3 months after RCC diagnosis did not significantly increase the risk of upstaging to pT3a cancer.

“During the current COVID-19 pandemic and subsequent recovery, urologists and their patients can expect delays in radical and partial nephrectomy for clinically localized RCC,” the researchers wrote in their journal paper. than alpha blockers. The findings held regardless of eGFR category.

Decreased Risk of Cardiac Events In addition, use of alpha blockers, compared with the use of other antihypertensive agents, was significantly associated with an 8% lower risk of cardiac events. Alpha blocker use was significantly associated with a 15% and 29% reduced risk of death among patients with an eGFR of 30-59 and less than 30, respectively.

The authors note that the study is limited by its observational design and a lack of detailed blood pressure (BP) measurement data.

“I think the current trial will sensitize physicians to the possibility that alpha blockers may have positive and negative effects beyond strict BP control,” commented Samuel N. Saltzberg, MD, associate professor of medicine at Rush

Allopurinol Dosage Reduction Increases Risk of Gout Flares

ALLOPURINOL DOSAGE reductions in patients hospitalized with acute gout are associated with an increased risk for gout flares within 3 months of discharge compared with no changes in dosage, according to study findings published in the Journal of Rheumatology.

Irvin J. Huang, DO, of the University of Washington in Seattle, Washington and colleagues studied 59 patients who had a diagnosis of gout and active prescriptions for allopurinol who were hospitalized for acute gout flares. The study population had a median age of 58 years, and 92% of patients were male.

The 59 patients had a total of 73 hospitalizations. Allopurinol was either reduced or discontinued in 15 admissions (allopurinol-reduced group), whereas the drug was increased or unchanged during the other 58 admissions (comparator group).

The proportion of patients with chronic kidney disease (CKD) was similar between the groups, but the allopurinol-reduced group had a greater proportion of patients with acute kidney injury vs the comparator group (60% vs 36%). The allopurinolreduced group had a significantly higher rate of gout flares within 3 months of discharge vs the comparator group (53% vs 22%).

The authors noted that dose reduction in their study was driven primarily by concerns that allopurinol use in patients with gout flares and renal insufficiency can worsen renal function and increase the risk of allopurinol hypersensitivity syndrome. They pointed out, however, that current studies support the safety of allopurinol use for gout patients with concurrent renal insufficiency. “Improved awareness of the current gout recommendations, as well as the risks and benefits of allopurinol in the setting of concomitant renal disease, is necessary to improve patient outcomes,” they wrote. ■

Medical College in Chicago. ■ “In most patients with clinically localized cT1b tumors, surgery may be safely delayed for up to 6 months without significant sacrifices in overall survival.”

For patients with cT2 tumors, they added, “we must carefully weigh tumor characteristics and patient comorbidities when discussing surgical delay. However, our data suggests that most patients experiencing a delay of 3 months due to the COVID-19 pandemic will not experience worse oncological outcomes.”

Among patients with cT1b lesions, a surgical delay of 1-3 months and more than 3 months was significantly associated with a 13% and 55% increased risk of death, respectively, compared with undergoing surgery within 1 month of diagnosis, in adjusted analyses, the researchers reported. They pointed out, however, that these patients still have favorable overall survival. Patients with surgical delays of 1-3 and more than 3 months have 5-year overall survival rates of 80.1% and 70.9%, respectively.

As surgical delay does not seem to predict upstaging, they noted, unmeasured confounding rather than tumor progression likely explains the adverse effect of delayed surgery on survival rates in patients with cT1b cancers. Surgical delay was not associated with worse survival among patients with cT2a or cT2b cancers. ■