2022 - Systemic Therapy for Bladder Cancer: Implications for the Urologist Flashcards
What types of systemic therapy are now included in the treatment of urothelial carcinoma?
In addition to standard chemotherapy, systemic therapy now includes immune checkpoint inhibition, FGFR tyrosine kinase inhibition, and antibody-drug conjugates (ADCs).
How many CPIs are FDA approved for urothelial cancer, and what are their names?
There are 4 CPIs FDA approved for urothelial cancer: Atezolizumab, Avelumab, Nivolumab, and Pembrolizumab.
What happened to Durvalumab’s approval for urothelial cancer?
Durvalumab was previously approved in the second-line (2L) setting, but approval was withdrawn when a phase III trial failed to meet the primary endpoint.
What was the change in approval for Atezolizumab in urothelial cancer treatment?
The FDA withdrew Atezolizumab’s second-line (2L) indication after failing to meet superiority over chemotherapy, but it remains approved in the first-line (1L) setting for chemotherapy-ineligible patients.
What is the standard first-line (1L) chemotherapy for metastatic or unresectable urothelial cancers?
Platinum-based chemotherapy, combined with gemcitabine and cisplatin or carboplatin. Accelerated methotrexate, vincristine, adriamycin, cisplatin is also a 1L choice.
What is the role of pembrolizumab in BCG-unresponsive nonmuscle-invasive bladder cancer (NMIBC)?
Pembrolizumab, a PD-1 inhibitor, is FDA-approved for patients with BCG-unresponsive CIS-containing NMIBC, with complete response observed in 40% of patients.
What are ADCs, and how might they be relevant to BCG-unresponsive bladder cancer in the future?
ADCs (Antibody-Drug Conjugates) target specific cancer cells, and studies suggest they may become a viable systemic option for patients with BCG-unresponsive bladder cancer.
What is the main concern for patients with residual muscle invasive and/or lymph node-positive urothelial cancer after surgery?
The main concern is the high risk of recurrence, leading to the evaluation of adjuvant immunotherapy.
What are the results of using nivolumab as adjuvant therapy, and is there a biomarker requirement?
Nivolumab has been FDA approved for a disease-free survival (DFS) rate of 22.9 months, compared to 13.7 months with placebo. There is no biomarker requirement, but a more profound effect was seen in patients with PD-L1+ tumors.
What findings were discovered regarding atezolizumab in the postoperative setting?
Atezolizumab failed to meet its primary DFS endpoint but demonstrated significant improvement in overall survival in patients with detectable circulating tumor DNA (+ctDNA), leading to a follow-up trial.
What is Avelumab, and how is it used in the context of urothelial cancer treatment?
Avelumab is a CPI tested and approved for maintenance therapy after achieving a clinical benefit following 1L platinum-based therapy. It’s administered IV every 2 weeks and has improved median overall survival.
What were the results of the Javelin 100 trial for Avelumab in comparison to observation?
The Javelin 100 trial found that Avelumab maintenance led to improved median overall survival of 21.4 versus 14.3 months for observation.
What precautions are needed when administering Avelumab, and why?
Avelumab carries an increased risk of infusion-related anaphylaxis. Patients are initially premedicated with Benadryl® and acetaminophen, and if no infusion-related events occur, subsequent treatments may be without premedication.
What options are available for patients with disease progression on or after 1L chemotherapy or those who defer avelumab maintenance?
For patients with disease progression, CPI therapy, including pembrolizumab, nivolumab, and avelumab, is approved in the 2L (second-line) and beyond setting.
How does pembrolizumab stand out among the CPI therapies for use in the 2L and beyond setting?
Pembrolizumab was associated with improved overall survival, better tolerance, and quality of life compared to chemotherapy. It carries level 1 evidence, indicating strong support for its effectiveness.