NICE recommends atezolizumab for metastatic urothelial cancer

5th October 2021

Atezolizumab has been approved by NICE for untreated advanced or metastatic urothelial cancer in adults where PD-L1 levels exceed 5%.

Urothelial carcinoma is the most common form of bladder cancer, accounting for more than 90% of all bladder cancers in the UK. The main symptom is haematuria in around 80% of cases although other symptoms include increased frequency of urination, pain or a burning sensation when passing urine and weight loss. According to Cancer Research UK, between 2016 and 2018, there were approximately 10,300 new cases of bladder cancer in the UK every year.

Atezolizumab is licensed as mono-therapy for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma, either after prior platinum-containing chemotherapy, or in patients who are cisplatin ineligible and whose tumours have a PD-L1 expression ≥ 5%. The checkpoint protein, programmed death-ligand 1 (PD-L1) which is present on the surface of tumour cells, normally binds to programmed death-1 (PD-1) on the surface of T-cells and prevents the T-cells from killing the tumour cells. Atezolizumab is a checkpoint inhibitor that prevents the binding of PD-L1 to PD-1 and thus restores tumour T-cell activity.

Clinical efficacy

Patients with advanced and metastatic urothelial carcinoma have a poor prognosis with 5-year survival rates as low as 6%. The standard treatment is cisplatin-based chemotherapy however, in a 2017 study 119 previously untreated patients who were cisplatin ineligible, were given atezolizumab at a dose of 1200 mg every 3 weeks until progression. The primary outcome was an objective response and which occurred in 23% of patients and a complete response was seen in 9%. The approval by NICE was based on more data, which came from IMvigor130, a multi-centre, Phase III trial, in which 1213 patients were randomised to either atezolizumab plus platinum-based chemotherapy, atezolizumab mono-therapy or placebo plus platinum-based chemotherapy. In its appraisal, NICE only considered a subgroup of 93 people, with untreated PD-L1-positive (tumour expression of 5% or more) locally advanced or metastatic urothelial cancer and who were ineligible to be treated with cisplatin.

The median overall survival was 18.6 months for atezolizumab and 10.0 months for platinum-based chemotherapy. The stratified hazard ratio was 0.50 (95% CI 0.29 to 0.87, p=0.0125), indicating that treatment with atezolizumab was associated with a significant improvement in overall survival compared with platinum-based chemotherapy. Moreover, the median progression-free survival for atezolizumab was 6.4 months compared with 6.0 months for platinum-based chemotherapy.

In its final appraisal document, NICE stated that “atezolizumab meets NICE’s criteria to be considered a life-extending treatment at the end of life. The cost-effectiveness estimates are likely to be within what NICE considers an acceptable use of NHS resources. So atezolizumab is recommended.“

Source. NICE 2021

Keratin 17 as a potential biomarker for urothelial carcinoma

8th June 2021

Urothelial carcinoma is the most common cancer of the urinary tract and while urine cytology is used to screen for the cancer, it has a low sensitivity, promoting the need for a more specific marker.

Urothelial carcinoma (UC) or transitional cell carcinoma, is the most common form of bladder cancer and is the tenth most common cancer in the world. The urothelial cells that line the bladder and urinary tract are constantly exposed to environmental agents that are filtered through the kidneys and not surprisingly, 90% of bladder cancers arise in these cells. Detection of UC is based on subjective microscopic features that are not always able to distinguish between benign and low-grade UC. Now a team from Yale Cancer Centre, US have developed a urine screening test based on immunocytochemistry and detects keratin 17, a molecule that has been found to be over-expressed in a range of cancers such as those affecting the breast, ovaries and pancreas. The researchers wanted to examine whether identification of keratin 17 could be used to screen for UC and detect recurrent UC in urine samples.

The study involved two patient cohorts: one with haematuria and one with recurrent UC. In screening samples with haematuria, the test was found to have a sensitivity of 100% and specificity of 83%. In patients with recurrent UC, the corresponding specificity and sensitivities were 92% and 100%.

The test itself, URO17 is developed by KDx diagnostics and commenting on the results of the study, co-author, Dr Nam Kim, said “there is now a growing body of evidence that the non-invasive K17 urine test will make a significant positive impact on detection and management of UC”. The study authors concluded that the study provides evidence to support the development of prospective trials to further define the clinical and diagnostic impact of K17.

Source

Babu S et al. Keratin 17 Is a Novel Cytologic Biomarker for Urothelial Carcinoma Diagnosis. Am J Clin Pathol 2021