In Focus: Peri-op Durvalumab+NACT in operable MIBC

The NIAGARA trial was a randomized phase 3 trial which randomised 1,063 patients from 22 countries into two groups in a 1:1 fashion, the Durvalumab group (533 patients) which received neoadjuvant gemcitabine–cisplatin chemotherapy combined with durvalumab, followed by radical cystectomy and adjuvant Durvalumab and the comparison group (530 patients) which received only neoadjuvant chemotherapy followed by radical cystectomy. In the durvalumab group, the patients received 4 cycles of neo-adjuvant Durvalumab (at a dose of 1500mg along with Gem-Cis as 3 weekly cycles and 8 cycles of Durvalumab was given as 4 weekly cycles as the adjuvant treatment post-cystectomy. The study’s primary endpoints were pathological complete response and Event-free survival (time until disease progression, recurrence, or death). The secondary endpoints included overall survival, treatment safety, and health-related quality of life. The study found that the pathological complete response (33.8% vs 25.8%, p=0.004; however, the criteria set was p<0.001) and the 24 month event free survival (67.8% vs 59.8%; p<0.001) was higher in the Durvalumab arm. Also, there were fewer deaths in the durvalumab arm (25.5% vs 31.9%, p=0.01) and the discontinuation rate of durvalumab combined with chemotherapy was similar to the chemotherapy arm (15.5%% vs 15.2%). The treatment related grade 3 or 4 adverse events were similar between the two groups (40.6% vs 40.9%) and treatment related death were reported to be similar in both the arms (0.6%). Immune mediated adverse events were reported in 20% of the patients who received Durvalumab. The study concluded that adding Durvalumab to neoadjuvant chemotherapy improved the event-free survival and showed a trend towards improved overall survival in patients with muscle-invasive bladder cancer and thus recommended Durvalumab as a potential new treatment option for cisplatin eligible patients. While the pathological complete response rate difference was not statistically significant, the early separation of Kaplan-Meier survival curves suggested a meaningful clinical benefit. Future research may explore biomarkers such as circulating tumor DNA (ctDNA) to refine patient selection for immunotherapy. 

Rapid review

New Drugs in India

This months rapid review focuses on 3 new drugs introduced in the Indian market in the recent times - darolutamide, relugolix and olaparib - and discusses there pharmacology as well as pharmacokinetics along with the warning and contra-indications. A short description about comparison with already available same class of drugs is also added.