FDA Pipeline: Priority Reviews for Immunotherapies in Gastric Cancers, Anal Cancer
The U.S. Food and Drug Administration (FDA) recently granted Priority Review to nivolumab as either adjuvant or first-line therapy in several types of gastric cancers, as well as to a novel PD-1 inhibitor for locally advanced or metastatic squamous cell carcinoma of the anal canal. The FDA also...
Feasibility Study of Radical Cystectomy vs Intravesical BCG for High-Grade, Non–Muscle Invasive Bladder Cancer
As reported in the Journal of Clinical Oncology by Catto et al, the BRAVO-Feasibility study showed that recruitment of patients with high-grade, non–muscle invasive bladder cancer into a randomized trial comparing radical cystectomy vs intravesical bacillus Calmette-Guérin (BCG) proved difficult,...
Germline-Somatic Interactions in Advanced Urothelial Cancer and Their Role in Disease Progression
In a study reported in Nature Communications, Bishoy M. Faltas, MD, of the Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, and colleagues identified common germline-somatic variant interactions in advanced urothelial cancer, with these...
Spectrum of Germline-Somatic Interactions in Advanced Urothelial Cancer
In a study reported in Nature Communications, Vosoughi et al identified common germline-somatic variant interactions in advanced urothelial cancer, with these interactions appearing to play a central role in disease progression. As stated by the investigators, “The prevalence and the biologic...
ESMO Immuno-Oncology 2020: Adjuvant Atezoliumab for Patients With Muscle-Invasive Urothelial Cancer and Presence of Postsurgical ctDNA
Patients with muscle-invasive urothelial cancer and postsurgical circulating tumor DNA (ctDNA) positivity have high risk of disease recurrence following cystectomy and experienced improved clinical outcomes with adjuvant atezolizumab as compared to patients undergoing observation. These...
DANUBE Trial Reports No Survival Benefit With First-Line Durvalumab in Metastatic Urothelial Carcinoma
As reported in The Lancet Oncology by Thomas Powles, MD, of Barts Cancer Institute, Queen Mary University of London, and colleagues, the phase III DANUBE trial showed that durvalumab monotherapy did not prolong overall survival vs standard chemotherapy in previously untreated patients with...
Expert Point of View: Kilian M. Gust, MD
Formal discussant Kilian M. Gust, MD, of the Medical University of Austria, Vienna, reminded listeners that JAVELIN Bladder 100 was designed at a time when no checkpoint inhibitor was approved for the treatment of metastatic urothelial cancer. In the past 5 years, five immune checkpoint inhibitors...
Front-Line Avelumab Maintenance Improved Survival Across Subgroups With Advanced Urothelial Carcinoma
A strategy of front-line maintenance treatment with the PD-L1 inhibitor avelumab combined with best supportive care improved both progression-free and overall survival vs best supportive care alone across prespecified subgroups of patients with advanced or metastatic urothelial carcinoma that had...
Expert Point of View: Richard Cathomas, MD
In his discussion of KEYNOTE-361 and the DANUBE trial, Richard Cathomas, MD, of Kantonsspital, Graubünden, Switzerland, said both studies yielded disappointing results. Overall, in these trials as well as current evidence from other trials, treatment of platinum-eligible (cisplatin or carboplatin)...
Checkpoint Inhibitor and Chemotherapy Combinations Fail to Move Bar as First-Line Therapy for Advanced Urothelial Cancer
Two different phase III studies found that combining an anti–PD-1/PD-L1 checkpoint inhibitor (pembrolizumab in KEYNOTE-361) with platinum-based chemotherapy or with another checkpoint inhibitor (the anti–CTLA-4 antibody tremelimumab in DANUBE) failed to significantly improve overall or...
Gemcitabine and Daily Radiation for Patients With Muscle-Invasive Bladder Cancer
Bladder preservation with trimodality therapy may be a safe and effective alternative to cystectomy for selected patients with muscle-invasive bladder cancer, according to results from a phase II trial presented by Coen et al at the virtual 2020 American Society for Radiation Oncology (ASTRO)...
Co-Leader of Immunotherapy Trial Reflects on ‘Practice-Changing’ Results in Advanced Bladder and Other Urinary Tract Cancers
In a large, randomized clinical trial, researchers evaluated the immunotherapy drug avelumab for patients with advanced urothelial cancer. The findings of the trial, called the JAVELIN Bladder 100 study, are “very exciting,” even “practice-changing,” said the trial’s co-leader, Petros Grivas, MD,...
Neoadjuvant Dual Checkpoint Blockade in Certain Patients With Localized Bladder Cancer
Neoadjuvant combination therapy with the anti–CTLA-4 therapy tremelimumab and the anti–PD-1 therapy durvalumab was well tolerated and showed early signs of activity in patients ineligible to receive cisplatin-based chemotherapy, all of whom had tumors with high-risk features that are associated...
Urine-Based Liquid Biopsy May Perform Similarly to Urine Cytology in Detecting Urothelial Carcinoma
Analysis of DNA copy number variants in the cells exfoliated in urine showed improved sensitivity and similar specificity in detecting urothelial carcinoma compared to urine cytology, according to results published by Zeng et al in Clinical Cancer Research. “Urine cytology, which is widely used to...
Nab-paclitaxel vs Paclitaxel in Platinum-Refractory Metastatic Urothelial Cancer
In a phase II trial reported in JAMA Oncology, Srikala S. Sridhar, MD, MSc, FRCPC, and colleagues found no difference in progression-free survival with nab-paclitaxel vs paclitaxel in patients with platinum-refractory metastatic urothelial cancer. Study Details In the investigator-initiated...
Avelumab Maintenance Therapy in Advanced or Metastatic Urothelial Carcinoma
In the phase III JAVELIN Bladder 100 trial reported in The New England Journal of Medicine, Thomas Powles, MD, PhD, and colleagues found that maintenance treatment with avelumab plus best supportive care significantly improved overall survival vs best supportive care alone among patients whose...
First-Line Durvalumab With or Without Tremelimumab vs Chemotherapy for Metastatic Urothelial Carcinoma
In the phase III DANUBE trial, reported in The Lancet Oncology, Thomas Powles, MD, PhD, and colleagues found that durvalumab monotherapy did not prolong overall survival vs standard chemotherapy in previously untreated patients with largely metastatic urothelial carcinoma with high PD-L1...
Early-Phase Trial Explores Cabozantinib and Nivolumab With or Without Ipilimumab in Advanced Genitourinary Malignancies
In a phase I trial reported in the Journal of Clinical Oncology, Andrea B. Apolo, MD, and colleagues found that the combination of cabozantinib and nivolumab, as well as the combination of cabozantinib/nivolumab plus ipilimumab, produced durable responses in patients with metastatic urothelial...
Maintenance Avelumab Plus Best Supportive Care in Advanced Bladder Cancer
Findings from the JAVELIN Bladder 100 trial were published by Thomas Powles, MD, and colleagues in The New England Journal of Medicine. Researchers reported that the PD-L1 inhibitor avelumab led to a 31% reduction in risk of death, and extended median survival by more than 7 months in patients with ...
Proton Pump Inhibitor Use May Be Associated With Worse Outcomes in Patients Treated With Atezolizumab for Urothelial Cancer
Recent evidence indicates that proton pump inhibitors may cause significant changes in the gut microbiota; gut microbiota dysbiosis has been linked to reduced immune checkpoint inhibitor effectiveness. In a retrospective analysis of clinical trials investigating the immune checkpoint inhibitor...
Cigarette Smoking Associated With Worse Outcomes for Patients With Bladder Cancer After Surgery
Patients treated for bladder cancer with a radical cystectomy have worse outcomes if they are smokers, according to a systematic review and meta-analysis by Keck Medicine of the University of Southern California (USC). The study appeared in The Journal of Urology.1 “This study is important because...
Avelumab in Maintenance Treatment of Urothelial Carcinoma
On June 30, 2020, avelumab was approved for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.1,2 Supporting Efficacy Data Approval was based on findings in the randomized, multicenter, ...
First-Line Atezolizumab Plus Platinum-Based Chemotherapy vs Chemotherapy Alone in Advanced Urothelial Cancer
As reported in The Lancet by Matthew D. Galsky, MD, of Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, and colleagues, the phase III IMvigor130 trial has shown prolonged progression-free survival with first-line atezolizumab plus platinum-based chemotherapy vs...
Long-Term Outcomes With Pembrolizumab for Cisplatin-Ineligible Advanced Urothelial Cancer
As reported in the Journal of Clinical Oncology by Jacqueline Vuky, MD, of Oregon Health & Science University, Portland, and colleagues, long-term follow-up in the phase II KEYNOTE-052 study has shown durable responses with first-line pembrolizumab in cisplatin-ineligible locally advanced or...
‘Switch Maintenance’ Pembrolizumab for Metastatic Urothelial Cancer
In a phase II study reported in the Journal of Clinical Oncology,1 Matthew D. Galsky, MD, of The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, and colleagues found that maintenance pembrolizumab produced additional responses and improved progression-free survival vs...
Novel Indications and New Drugs for the Treatment of Bladder Cancer
Pembrolizumab: On January 8, 2020, pembrolizumab (Keytruda) was approved by the U.S. Food and Drug Administration (FDA) for bacillus Calmette-Guérin (BCG)-unresponsive, high-risk, non–muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors who are ineligible for or...
Early Data Show Activity for Enfortumab Vedotin Plus Pembrolizumab in Advanced Bladder Cancer
It may be possible to use a platinum-free combination as first-line treatment for advanced or metastatic urothelial carcinoma in cisplatin-ineligible patients, if the results of the phase Ib/II EV-103 trial hold up. The combination of the newly approved antibody-drug conjugate (enfortumab vedotin)...
Erdafitinib in FGFR-Altered Advanced Urothelial Carcinoma
As reported in The New England Journal of Medicine by Loriot et al, the fibroblast growth factor receptor 1-4 tyrosine kinase inhibitor erdafitinib showed activity in FGFR-altered advanced urothelial carcinoma.1 The study enrolled patients from sites in 14 countries between May 2015 and March 2018. ...
Maintenance Avelumab Improves Survival in Advanced Bladder Cancer
Maintenance therapy with avelumab and best supportive care significantly prolonged overall survival vs best supportive care alone in patients with advanced urothelial carcinoma that did not progress on first-line platinum-based chemotherapy, according to an interim analysis of the phase III JAVELIN ...
Genitourinary Oncology Highlights 2019–2020 Almanac
Over the past year, we have seen significant advances in the treatment of prostate, kidney, and urothelial cancers that will benefit patients now and in the future. We have learned about the final results of important clinical trials across multiple genitourinary cancers disease states leading to...
Cabozantinib in Platinum-Refractory Metastatic Urothelial Carcinoma
In a single-center phase II trial reported in The Lancet Oncology, Andrea Apolo, MD, and colleagues found that the multikinase inhibitor cabozantinib showed activity in a cohort of patients with platinum-refractory metastatic urothelial carcinoma. As noted by the investigators, in addition to...
Expert Point of View: Daniel Y. Heng, MD, MPH, and Toni K. Choueiri, MD
Study discussant Daniel Y. Heng, MD, MPH, a medical oncologist at Tom Baker Cancer Centre, University of Calgary, Canada, called the negative trial results important. IMvigor010 randomly assigned patients with high-risk muscle-invasive urothelial carcinoma to adjuvant atezolizumab or observation...
Adjuvant Atezolizumab Fails to Meet Primary Study Endpoint in High-Risk Bladder Cancer
Adjuvant atezolizumab, a PD-L1–blocking antibody, failed to meet the primary endpoint of disease-free survival in patients at high risk of recurrence of muscle-invasive bladder cancer compared with observation alone, according to the primary analysis of the IMvigor010 trial reported during the...
Expert Point of View: Jonathan E. Rosenberg, MD
“These data are solid, showing a 7-month improvement in overall survival in patients with stable disease or better after first-line chemotherapy. This is roughly a 50% improvement in survival, which is clinically meaningful. Also, progression-free survival was significantly increased with...
Advanced Bladder Cancer Survival Improved With Maintenance Avelumab
According to an interim analysis of the phase III JAVELIN Bladder 100 trial, rates of survival among patients with advanced urothelial carcinoma who did not progress on first-line platinum-based chemotherapy were significantly prolonged by maintenance therapy with avelumab and best supportive care...
Conference Highlights From the ASCO20 Virtual Scientific Program
The global outbreak of the COVID-19 pandemic forced many cancer societies, including ASCO, to cancel their in-person meetings this year and instead present the latest advancements and new approaches in oncology care via a virtual platform. For the first time in its 56-year history, the ASCO Annual...
FDA Approves Maintenance Avelumab for the Treatment of Advanced Urothelial Carcinoma
On June 30, the U.S. Food and Drug Administration (FDA) approved avelumab (Bavencio) for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy. JAVELIN Bladder 100 Efficacy of avelumab...
Biomarker Combination May Help Predict Response to Immunotherapy in Patients With Metastatic Urothelial Carcinoma
In patients with metastatic urothelial carcinoma, a novel combination of biomarkers from baseline tumor tissues was predictive of improved clinical responses and prolonged survival following treatment with immune checkpoint inhibitors, according to findings published by Goswami et al in Science...
Long-Term Outcomes With Pembrolizumab for Cisplatin-Ineligible Advanced Urothelial Cancer
As reported in the Journal of Clinical Oncology by Vuky et al, long-term follow-up in the phase II KEYNOTE-052 study has shown durable responses with first-line pembrolizumab in cisplatin-ineligible locally advanced or metastatic urothelial cancer, with higher response rates and longer survival in...
IMvigor130: First-Line Atezolizumab Plus Chemotherapy vs Chemotherapy Alone in Advanced Urothelial Cancer
As reported in The Lancet by Matthew D. Galsky, MD, of Icahn School of Medicine at Mount Sinai, and colleagues, the phase III IMvigor130 trial has shown prolonged progression-free survival with first-line atezolizumab plus platinum-based chemotherapy vs platinum-based chemotherapy alone in patients ...
Christopher Sweeney, MBBS, and Thomas Powles, MD, PhD, on Urothelial Cancer: The JAVELIN Bladder 100 Study on Avelumab vs Best Supportive Care
Christopher Sweeney, MBBS, of Dana-Farber Cancer Institute, talks with Thomas Powles, MD, PhD, of Queen Mary University of London, about the first study to demonstrate a survival advantage with avelumab for metastatic urothelial cancer. In the trial, avelumab improved median overall survival by 21.4 months compared with 14.3 months with best supportive care (Abstract LBA1).
Expert Point of View: Jonathan E. Rosenberg, MD
“These data are solid, showing a 7-month improvement in overall survival in patients with stable disease or better after first-line chemotherapy. This is roughly a 50% improvement in survival, which is clinically meaningful. Also, progression-free survival was significantly increased with...
Maintenance Avelumab Improves Survival in Advanced Bladder Cancer
Maintenance therapy with avelumab and best supportive care significantly prolonged overall survival vs best supportive care alone in patients with advanced urothelial carcinoma that did not progress on first-line platinum-based chemotherapy, according to an interim analysis of the phase III...
Mitomycin Gel for Low-Grade Upper Tract Urothelial Cancer
On April 15, 2020, mitomycin gel was approved for the treatment of adult patients with low-grade upper tract urothelial cancer.1,2 Mitomycin gel is for pyelocalyceal use alone and not for intravenous, topical, or oral administration. Supporting Efficacy Data Approval was based on findings in the...
Metastatic Urothelial Cancer: A Conversation on State-of-the-Art Treatment Before the ASCO20 Virtual Scientific Program
As Thomas Powles, MD, PhD, of Queen Mary University of London, prepares to deliver his late-breaking presentation at the ASCO20 Virtual Scientific Program (LBA-1), he talks with Christopher Sweeney, MBBS, of Dana-Farber Cancer Institute, about current therapy: PD1/PDL1 inhibition in second-line treatment and as monotherapy in the first-line setting, as well as the concept of maintenance switch.
Low-Intensity Surveillance as an Option for Some Patients With Non–Muscle Invasive Bladder Cancer
Low-intensity cystoscopic surveillance may be a viable option for patients with high-risk, non–muscle invasive bladder cancer, according to data from a paper presented to the media during a special session moderated by the American Urological Association (AUA) on May 15. The research was also...
Chemoablation of Low-Grade Upper Tract Urothelial Cancer With Mitomycin-Containing Reverse Thermal Gel
In the single-arm phase III OLYMPUS trial reported in The Lancet Oncology, Kleinmann et al found that primary chemoablation of low-grade upper tract urothelial carcinoma using a mitomycin-containing reverse thermal gel (UGN-101) resulted in disease eradication in more than half of patients. As...
'Switch Maintenance' Pembrolizumab for Metastatic Urothelial Cancer
In a phase II study reported in the Journal of Clinical Oncology, Matthew D. Galsky, MD, and colleagues found that maintenance pembrolizumab produced additional responses and improved progression-free survival vs placebo in patients with metastatic urothelial cancer who had at least stable disease...
FDA Approves Mitomycin Gel for Low-Grade Upper Tract Urothelial Cancer
On April 15, the U.S. Food and Drug Administration (FDA) approved mitomycin (Jelmyto) for adult patients with low-grade upper tract urothelial cancer. OLYMPUS Trial Efficacy determination was based on OLYMPUS, an ongoing, single-arm, multicenter trial enrolling 71 patients with treatment-naive or...
FDA Pipeline: Priority Reviews for Immunotherapy Based on Biomarker Status, Combination First-Line Therapy in Lung Cancer
Over the past week, the U.S. Food and Drug Administration (FDA) granted Priority Review to an immunotherapeutic agent for solid tumors with a high tumor mutational burden and to a combination treatment for the first-line treatment of metastatic or recurrent non–small cell lung cancer. The agency...
