The National Institute for Clinical Excellence has issued final guidance supporting the use of atezolizumab for patients with treatment-naïve, PD–L1–positive locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin.
The National Institute for Clinical Excellence (NICE) has issued final guidance supporting the use of atezolizumab (Tecentriq) for patients with treatment-naïve, PD-L1–positive locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin.1
NICE concluded that atezolizumab was associated with statistically significant improvements in median overall survival (OS) and median progression-free survival (PFS) compared with chemotherapy in patients with a PD-L1 expression of 5% or greater.
“I am pleased we are able to recommend this life-extending treatment for people with this form of urothelial cancer. The independent appraisal committee heard from the clinical and patient experts that there is an unmet clinical need for people with this form of cancer,” Meindert Boysen, deputy chief executive and director of the Centre for Health Technology Evaluation at NICE, stated in a news release. “They also recognized that people value additional treatment options which have a positive impact not just in terms of extending their life, but in improving their quality of life too.”
Urothelial carcinoma accounts for 90% of bladder cancers in the United Kingdom. Cancer Research UK estimates that there have been, on average, 10,300 diagnoses of bladder cancer annually from 2016 to 2018.2
NICE evaluates drugs for cost efficiency. For a life-extending treatment at the end of life, the upper limit for cost-effective use of National Health Service resources is £50,000 ($67,358) per quality-adjusted life year (QALY) gained. NICE concluded that the incremental cost-effectiveness ratio for atezolizumab was £32,235 ($43,424) per QALY gained.
The list price for atezolizumab is £3,807.69 ($5,121.50) per 1200-mg vial. Roche has agreed to offer the drug at a discount, the size of which has not been disclosed.
NICE’s decision is based on findings from the phase 3 IMvigor130 trial (NCT02807636), which evaluated atezolizumab monotherapy versus chemotherapy as frontline treatment in patients with cisplatin-ineligible IC2/3 advanced or metastatic metastatic urothelial carcinoma. The trial included 1213 patients, but this approval concerns only a subset of 93 PD-L1–high patients.
In this subgroup, the median OS was 18.6 months with atezolizumab and 10.0 months withplatinum-based chemotherapy (HR, 0.50; 95% CI, 0.29-0.87; P = .0125). The median PFS was 6.4 months vs 6.0 months, respectively (HR, 0.56; 95% CI 0.34-0.93, P = .0235).3
In April 2021, the FDA’s Oncologic Drugs Advisory Committee voted 10 to 1 to support the accelerated approval of atezolizumab for use in the frontline treatment of patients with cisplatin-ineligible metastatic urothelial carcinoma based on results from IMvigor130.4
An exploratory analysis presented during the 2021 Genitourinary Cancers Symposium compared cisplatin-ineligible patients randomly assigned to atezolizumab plus platinum/gemcitabine chemotherapy (arm A), atezolizumab monotherapy (arm B), and platinum/gemcitabine chemotherapy alone (arm C) based on PD-L1 status. The study protocol was altered to only allow administration of atezolizumab to cisplatin-ineligible patients whose tumors had a high PD-L1 score, instead of the full study population.5
When accounting for cisplatin-ineligible patients, those classified at IC2/3 saw a greater OS benefit in arm B compared with arm C (HR, 0.53; 95% CI, 0.30-0.94); patients classified at IC0/1 did not (HR, 1.11; 95% CI, 0.82-1.51). The objective response rate (ORR) for patients in arm B was 38% (95% CI, 25%-53%) compared with 33% in arm C (95% CI, 19%-49%). Twenty-one OS events were reported among the 50 patients on arm B vs 26 OS events in the 43 patients on arm C.
Interim OS data for atezolizumab monotherapy could not be formally tested, but investigators observed favorable efficacy in patients with IC2/3 metastatic urothelial carcinoma at a median of 15.7 months (95% CI, 13.1-17.8). Moreover, this benefit was consistent irrespective of cisplatin eligibility and PD-L1 score in both OS (HR, 1.02; 95% CI, 0.83-1.24) and ORR, with an ORR of 23% (95% CI, 19%-28%) in the atezolizumab monotherapy arm and 43% (95% CI, 38%-49%) in the placebo and chemotherapy arm.6