In patients with muscle-invasive bladder cancer, gemcitabine plus once daily radiation showed a low cystectomy rate and high overall survival rate at long-term follow-up.
Gemcitabine plus once daily radiation (GD) continued to achieve a low cystectomy rate and high overall survival (OS) rate in selected patients with muscle-invasive bladder cancer (MIBC), according to long-term follow-up data from the phase 2 NRG-RTOG 0712 trial presented during the 2020 ASTRO Annual Meeting.1,2
The study evaluated both the GD regimen and the previous standard of fluorouracil plus cisplatin and radiation twice a day (FCT). The results showed that the 2 regimens were equally effective at a median follow-up time of 7.3 years. The rate of freedom from distant metastasis at 3 years was 79% with FCT versus 85% with GD. The rates at 5 years were 70% versus 77%, respectively.
The 3-year bladder-intact distant metastasis free rates were 67% with FCT versus 72.5% with GD, and the 5-year rates were 65.1% versus 72.5% respectively. In the FCT cohort, the post-induction complete response (CR) rate was 88% versus 76% in the GD arm. The 5-year OS rates were 74% versus 71%, respectively.
The study was not powered to compare the 2 regimens head-to-head; however, it was observed that the safety profile was better in the GD arm.
“Not only did this trial conclude that gemcitabine and daily radiation is an acceptable regimen with favorable distant metastasis free rates at 3 years, the results also indicate that both treatments maintain their high rates of distant metastasis free at 5 years and both treatments had low cystectomy rates with high overall survival rates,” John J. Coen, MD, of 21st Century Oncology and the principal investigator of the NRG-RTOG 0712 study, stated in a press release.
“The efficacy of the GD regimen may facilitate wider adoption of bladder preservation as many patients have comorbidities that preclude the use of cisplatin. The daily radiation schedule is also easier for patients and treatment centers to administer than twice daily treatment which will also likely increase interest in this strategy. These findings are important to future trials that may assess a systemic therapy for this muscle-invasive bladder cancer,” added Coen.
From December 2008 to April 2014, the study enrolled 70 patients with cT2-4a MIBC. Patients were randomized to FCT or GD. All patients received transurethral resection and induction chemoradiotherapy (CRT) to 40 Gy. Patients who had a CR then received consolidation CRT to 64 Gy; those who did not achieve a CR underwent cystectomy. Gemcitabine/cisplatin was administered as adjuvant chemotherapy.
Among the 70 randomized patients, 66 (33 in each arm) were eligible for the efficacy and safety analyses. Of the 66 patients, 3 patients in the FCT arm and 6 patients in the GD arm underwent cystectomy.
Grade 3/4 treatment-related adverse events (AEs) occurred in 58% (19 patients) of the FCT arm compared with 52% (17 patients) of the GD arm. The number of patients in each arm experiencing grade 3/4 hematologic and gastrointestinal AEs in each arm was 18 versus 14 and 2 versus 3 in the FCT and GD arms, respectively. Additionally, 2 patients in each arm had grade 3/4 genitourinary AEs.
1. Updated Results of NRG Oncology Trial Display Effectiveness of Gemcitabine and Daily Radiation for Bladder Preservation in Muscle-Invasive Bladder Cancer Patient. Published Online October 25, 2020. https://bit.ly/35CmS0k Accessed October 27, 2020.
2. Coen JJ, Rodgers J, Saylor PJ, et al. Bladder preservation with twice-daily radiation plus 5-flourouracil/cisplatin or daily radiation plus gemcitabine for MIBC – updated results of NRG/RTOG 0712: a randomized phase 2 trial.Int J Radiat Oncol Biol Phys. 2020;108(3):S28-S29. doi: 10.1016/j.ijrobp.2020.07.2122.