KEY TAKEAWAYS
- The Phase 3 IMvigor010 study was a multicentre, open-label, randomized trial with a ClinicalTrials.gov identifier of NCT02450331.
- The primary aim of this study was to determine whether atezolizumab was effective as adjuvant therapy for individuals with high-risk muscle-invasive urothelial carcinoma.
- Patients with histologically confirmed muscle-invasive urothelial carcinoma were enrolled within 14 weeks after radical cystectomy or nephroureterectomy with lymph node dissection.
- The primary measure of success was disease-free survival, which was significantly longer with atezolizumab than with observation.
- Patients who received neoadjuvant chemotherapy had tumors that were ypT2-4a or ypN+, while those without neoadjuvant chemotherapy had tumors that were pT3-4a or pN+.
- Atezolizumab was effective as adjuvant therapy for high-risk muscle-invasive urothelial carcinoma, resulting in significantly longer disease-free survival than observation.
Standard curative-intent treatment for muscle-invasive urothelial carcinoma consists of neoadjuvant cisplatin-based chemotherapy, followed by radical surgery in suitable patients; nonetheless, a substantial recurrence persists despite the lack of level 1 evidence for adjuvant therapy. Researchers intended to determine if atezolizumab was effective as adjuvant therapy for individuals with high-risk muscle-invasive urothelial carcinoma. Patients 18 and older with histologically confirmed muscle-invasive urothelial carcinoma and an Eastern Cooperative Oncology Group performance status of 0, 1, or 2 were enrolled within 14 weeks after radical cystectomy or nephroureterectomy with lymph node dissection in the IMvigor010 study, a multicentre, open-label, randomized, phase 3 trial done in 192 hospitals, academic centers, and community oncology practices across 24 countries or regions. Following neoadjuvant chemotherapy, patients had tumors that were ypT2-4a or ypN+, while those without neoadjuvant chemotherapy had tumors that were pT3-4a or pN+. Neoadjuvant chemotherapy is given to patients who are either not candidates for or refuse cisplatin-based adjuvant treatment. Neither adjuvant chemotherapy nor radiotherapy administered after surgery was permitted. Patients were randomly randomized (1:1) to receive 1200 mg of atezolizumab intravenously every three weeks for 16 cycles or up to 1 year, whichever came first, or to observation utilizing a permuted block (block size of four) approach and an interactive voice-web response system. The number of lymph nodes removed, the pathological quality of the lymph nodes, the tumor’s stage, and the presence of PD-L1 on infiltrating immune cells all affected how patients were randomly assigned to treatment.
In the study’s intended-treatment population, disease-free survival was the primary measure of success. Patients who had at least one post-baseline safety evaluation or received at least one dose of atezolizumab were included in the safety analysis. ClinicalTrials.gov identifier: NCT02450331; currently, recruitment is completed. Researchers enrolled 809 patients between October 5, 2015, and July 30, 2018, with 406 patients receiving atezolizumab and 403 receiving observation. The average time between visits was 21.9 months (IQR: 13.8–29.8). Disease-free survival was significantly longer with atezolizumab (19.4 months, 95% confidence interval [CI] 15.9 to 24.8 months) than with observation (16.8 months, 95% CI 11.2 to 24.8 months) (stratified hazard ratio 0.89, 95% CI 0.74 to 1.08, P=0.24). UTIs (31 [8%] of 390 patients in the atezolizumab group and 20 [5%] of 397 patients in the observation group), pyelonephritis (12 [3%]) and anemia (eight [2%]) were the most common side events of grade 3 or 4. Twelve patients receiving atezolizumab (31%) and seventy-one patients under monitoring (18%) experienced severe adverse events. Sixty-three patients (16%) who were given atezolizumab experienced a treatment-related adverse event of grade 3 or 4. Acute respiratory distress syndrome was the cause of death in one patient in the atezolizumab group.
Source:https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00004-8/fulltext
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02450331
Joaquim Bellmunt,Prof Maha Hussain, Prof Jürgen E Gschwend, Prof Peter Albers, Prof Stephane Oudard, Daniel Castellano, Siamak Daneshmand, Prof Hiroyuki Nishiyama, MD
Martin Majchrowicz, Viraj Degaonkar, Yi Shi, Sanjeev Mariathasan, Petros Grivas, Alexandra Drakaki, Peter H O’Donnell, Prof Jonathan E Rosenberg, Daniel M Geynisman, Prof Daniel P Petrylak, Jean Hoffman-Censits, Prof Jens Bedke, Arash Rezazadeh Kalebasty, Yousef Zakharia, Michiel S van der Heijden, Prof Cora N Sternberg, Nicole N Davarpanah, Prof Thomas Powles/Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomized, phase 3 trial/https://doi.org/10.1016/S1470-2045(21)00004-8
