The Therapeutic Goods Administration has approved pembrolizumab (KEYTRUDA 200mg, every three weeks) as monotherapy for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing therapy or those who have previously received platinum-containing chemotherapy.
Medical oncologists have welcomed the new use for pembrolizumab anti-PD-1 immunotherapy, describing it as “the first new treatment option in Australia for advanced bladder cancer in more than thirty years”.
Professor Howard Gurney from Macquarie University Hospital who was involved in the single-arm clinical trial for urothelial carcinoma, said he was “delighted” that the anti-PD-1 immunotherapy is now approved for treatment in Australia for patients with this form of advanced bladder cancer.
“Chemotherapy has been the mainstay of treatment for decades in bladder cancer so it is tremendously exciting to use immunotherapy in treatment protocols for these patients,” he said.
“A significant proportion of bladder cancer patients respond to immunotherapy compared to chemotherapy after platinum-based therapy, and this represents an important new treatment paradigm for these patients,” Professor Howard Gurney
More than 2,500 new cases of bladder cancer are diagnosed in Australia each year, with urothelial cancer claiming more than 1,000 Australian lives annually. The cancer has a five-year survival rate of only 53 per cent.
More than 40 per cent of patients with advanced urothelial cancer who are 70 years or older cannot receive standard, first-line cisplatin-based chemotherapy due to impaired renal function.
TGA approval of Keytruda for locally advanced or metastatic urothelial carcinoma for first line treatment has been granted based on overall response, duration of response and safety data from the KEYNOTE-052 trial.
The first-line approval is based on data from KEYNOTE-052, which investigated KEYTRUDA in 370 patients with locally advanced or metastatic urothelial carcinoma who were not eligible for cisplatin-containing chemotherapy. The objective response rate was 29 per cent (95%CI 24,34) with a complete response rate of 7 per cent and a partial response rate of 22 per cent. The median response duration was not reached (95% CI 1.4+, 17.8+). 19 per cent of patients experience a duration of greater or equal to 6 months and the median time to response was 2 months (95%CI 1.6,4.8).
The approval for treatment after platinum-containing chemotherapy is based on data from KEYNOTE-045, which investigated pembrolizumab in 542 patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy versus investigator choice of chemotherapy with paclitaxel, docetaxel or vinflunine. The coprimary end points were overall survival and progression-free survival in all patients in the trial and in patients with a PD-L1 tumour proportion score of 10 per cent or more. The median overall survival was 10.3 months (95% CI, 8.0 to 11.8) for patients treated with KEYTRUDA, compared with 7.4 months (95% CI, 6.1 to 8.3) for patients treated with chemotherapy.
The estimated overall survival rate at 12 months was 43.9 per cent (95% CI, 37.8 to 49.9) in the pembrolizumab group, compared with 30.7 per cent (95% CI, 25.0 to 36.7) in the chemotherapy group. Overall, there was no significant difference between pembrolizumab and chemotherapy with regard to progression-free survival (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19, P=0.42).6
In terms of secondary endpoints, the complete response rate was 21.1 per cent (95% CI, 16.4 to 26.5), for patients treated with pembrolizumab , significantly higher than the 11.4 per cent response rate for patients treated with chemotherapy (95% CI, 7.9 to 15.8) (P = 0.001).
Pembrolizumab is a humanised monoclonal antibody that reactivates the immune system to attack tumour cells by blocking the programmed cell death protein; which left unchecked allows cancer cells to pass undetected by the body’s natural defences.
Pembrolizumab is now registered for the treatment of advanced forms of bladder cancer, head and neck cancer, classical Hodgkin Lymphoma, non-small cell lung cancer and melanoma. It is currently only PBS listed for metastatic melanoma patients. MSD confirmed that its priority is to ensure affordable access as early as possible for Australians who may benefit from pembrolizumab and will continue to work with the Federal Government to achieve this outcome.
Source: Ethical Strategies