Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer
Is this the end of the cisplatin era in bladder cancer? It sure seems that way. The results here are no surprise based on the signal we saw in the metastatic setting.
ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer
Author(s): Thomas Powles, M.D.1; Ariel G. Kann, M.D.2; Daniel Castellano, M.D.3; Marine Gross-Goupil, M.D., Ph.D.4; Hiroyuki Nishiyama, M.D., Ph.D.5; Sergio Bracarda, M.D.6; Jørgen Bjerggaard Jensen, M.D.7; Lydia Makaroff, Ph.D.8,9; Shusuan Jiang, M.D.10; Ja Hyeon Ku, M.D., Ph.D.11; Se Hoon Park, M.D., Ph.D.12; Oscar Reig Torras, M.D., Ph.D.13; Dingwei Ye, M.D., Ph.D.14; Marco Maruzzo, M.D., Ph.D.15; Andrea Necchi, M.D.16,17; Rafael Morales-Barrera, M.D.18; Emilio Francesco Giunta, M.D., Ph.D.19; Jae Lyun Lee, M.D., Ph.D.20; Giampaolo Tortora, M.D., Ph.D.21,22; Yüksel Ürün, M.D.23; Lukasz Dolowy, M.D., Ph.D.24; Dilek Erdem, M.D.25; Alvaro Pinto, M.D., Ph.D.26; Fabricio Grando, M.D.27; Wei Zou, Ph.D.28; Zoe June Assaf, Ph.D.28; Jacqueline Vuky, M.D.28; Viraj Degaonkar, Pharm.D.6,28; Elizabeth E. Steinberg, Ph.D.28; Joaquim Bellmunt, M.D., Ph.D.29; Jürgen E. Gschwend, M.D., Ph.D.30; the IMvigor011 Investigators*;
Source: DOI: 10.1056/NEJMoa2511885
Dr. Maen Hussein's Thoughts
Circulating tumor DNA (ctDNA) was used to identify patients who may benefit from adjuvant immunotherapy. Among ctDNA-positive patients, those who received adjuvant atezolizumab demonstrated improved progression-free survival (PFS) and overall survival (OS) compared with placebo (median OS, 32 vs 24 months). Patients with persistently negative ctDNA results had 1-year disease-free survival (DFS) of 95% and 2-year DFS of 88%.
BACKGROUND
Patients with muscle-invasive bladder cancer have varied outcomes after cystectomy. Circulating tumor DNA (ctDNA)–based detection of molecular residual disease may identify patients high risk for recurrence after cystectomy who can benefit from adjuvant immunotherapy, thus sparing patients lower risk from unnecessary treatment burden.
METHODS
In a phase 3, double-blind, randomized trial, we used serial ctDNA testing to monitor (for up to 1 year) patients with muscle-invasive bladder cancer and no radiographic evidence of disease after surgery. Eligible patients who tested ctDNA-positive during surveillance were randomly assigned in a 2:1 ratio to receive intravenous atezolizumab or placebo every 4 weeks for up to 1 year. The primary end point was investigator-assessed disease-free survival. Overall survival was a secondary end point that was assessed in a hierarchical fashion to control for alpha. Patients who persistently tested ctDNA-negative did not receive atezolizumab or placebo. Research Summary ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer
RESULTS
A total of 761 patients were enrolled; 250 eligible patients who tested ctDNA-positive underwent randomization (167 to the atezolizumab group and 83 to the placebo group). The median disease-free survival was 9.9 months with atezolizumab, as compared with 4.8 months with placebo (hazard ratio for first event of disease recurrence or death, 0.64; 95% confidence interval [CI], 0.47 to 0.87; P=0.005). The median overall survival was 32.8 months with atezolizumab, as compared with 21.1 months with placebo (hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P=0.01). A total of 28% of the patients who received atezolizumab and 22% of those who received placebo had adverse events of grade 3 or 4 (related to atezolizumab or placebo in 7% vs. 4%); 3% and 2% of the patients, respectively, had fatal adverse events (related to atezolizumab or placebo in 2% vs. none). Among 357 patients with persistent ctDNA-negative status, disease-free survival was 95% the end of the 1-year monitoring period and 88% 2 years.
CONCLUSIONS
Among patients with muscle-invasive bladder cancer, ctDNA-guided adjuvant therapy with atezolizumab led to significantly longer disease-free survival and overall survival than placebo. (Funded by F. Hoffmann–La Roche; IMvigor011 ClinicalTrials.gov number, NCT04660344.)
Author Affiliations
1Barts Cancer Institute, National Institute for Health Research Biomedical Research Centre, Queen Mary University of London, London; 2Hospital Alemão Oswaldo Cruz, São Paulo; 3Hospital Universitario 12 de Octubre, Madrid; 4University Hospital of Bordeaux, Bordeaux, France; 5University of Tsukuba, Tsukuba, Japan; 6Azienda Ospedaliera Santa Maria, Terni, Italy; 7Aarhus University, Aarhus, Denmark; 8Fight Bladder Cancer, Chinnor, United Kingdom; 9World Bladder Cancer Patient Coalition, Brussels; 10Hunan Cancer Hospital, Changsha, China; 11Seoul National University Hospital, Seoul, South Korea; 12Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 13Department of Medical Oncology, Institut d’Investigacions Biomèdiques August Pi I Sunyer, Hospital Clinic, Barcelona; 14Fudan University Shanghai Cancer Center, Shanghai; 15Istituto Oncologico Veneto, IRCCS, Padua, Italy; 16Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan; 17Vita-Salute San Raffaele University, Milan; 18Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona; 19Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori,” IRCCS, Meldola, Italy; 20Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea; 21Medical Oncology Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome; 22Medical Oncology Unit, Università Cattolica del Sacro Cuore, Rome; 23Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey; 24University Clinical Hospital, Warsaw, Poland; 25Istinye University Medical Faculty, Istanbul, Turkey; 26University Hospital La Paz, Madrid; 27Centro de Pesquisas Oncológicas, Florianópolis, Brazil; 28Genentech, South San Francisco, CA; 29Dana–Farber Cancer Institute and Harvard University, Boston; 30Technical University Munich, Munich, GermanyRelated Articles
Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer
At 2 years, estimated event-free survival was 74.7% in the enfortumab vedotin–pembrolizumab group and 39.4% in the control group (hazard ratio) HR 0.4 estimated overall survival was 79.7% and 63.1% HR 0.50. Perioperative enfortumab vedotin plus pembrolizumab new standard of care for cisplatin ineligible patients who are candidates for surgery.
Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926
Trimodality therapy is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder.
Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer
Perioperative durvalumab showed an improvement of 2-year OS of 82.2 vs 75.2%, 2-year PFS was improved 67.8 vs 59.8%. There was interestingly no difference in the rates of grade 3-4 toxicity in the SOC vs periop-IO group. This is likely going to become the SOC in resectable bladder cancer.
Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer
Many had neoadjuvant therapy, still no difference between standard or extended lymphadenectomy for muscle-invasive bladder cancer. So, it seems more is not better.