Review: Checkpoint Inhibitors and Other Immunotherapies in Urologic Cancer
Key findings
- This review outlines immune-based therapy options for renal cell carcinoma (RCC), bladder cancer, and prostate cancer
- Pembrolizumab is recommended as adjuvant treatment for certain cases of localized clear cell RCC
- In combination with other agents, pembrolizumab and nivolumab are FDA-approved for first-line treatment of advanced clear cell RCC, but response rates in non–clear cell RCC are poorer
- Four checkpoint inhibitors are now indicated for advanced bladder cancer, and enfortumab vedotin, an antibody–drug conjugate, is FDA-approved for metastatic bladder cancer refractory to platinum chemotherapy and checkpoint inhibitor therapy
- For treatment of metastatic castrate-resistant prostate cancer, sipuleucel-T or pembrolizumab are options in some instances, and the combination of nivolumab and ipilimumab shows promise
Immunotherapies, including monoclonal antibodies, checkpoint inhibitors, vaccines, and drug–antibody conjugates, have revolutionized the treatment of urologic cancers over the past two decades.
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In Urologic Clinics of North America, Aleksandra Walasek, MD, a clinical fellow in Surgery in the Department of Urology at Massachusetts General Hospital, and Dimitar V. Zlatev, MD, urologic surgeon in the Department and urologic oncologist at the Mass General Cancer Center, review the evidence underlying the latest recommendations.
Localized Clear Cell Renal Cell Carcinoma (RCC)
Pembrolizumab is recommended as adjuvant treatment for patients with:
- Stage 2 clear cell RCC and grade 4 or sarcomatoid high-risk features
- Stage 3 clear cell RCC
- Stage 4 clear cell RCC along with resection of metastatic lesions and within one year of nephrectomy
Advanced Clear Cell RCC
The checkpoint inhibitors currently used as first-line therapy for advanced or metastatic clear cell RCC are part of combination regimens:
- Nivolumab plus ipilimumab is FDA-approved as the first-line treatment of intermediate- and poor-risk advanced clear cell RCC
- Nivolumab plus cabozantinib, and pembrolizumab plus axitinib, are FDA-approved as first-line therapy for advanced clear cell RCC
Non–Clear Cell RCC
Pembrolizumab and nivolumab have been studied as monotherapy in non–clear cell RCC, but response rates are substantially lower than for clear cell RCC.
Non–Muscle-invasive Bladder Cancer
Pembrolizumab is an option based on results of a recent phase 2 trial (published in The Lancet) in patients treated for high-risk cancer in situ (with or without solid papillary tumor) who had not responded to Bacillus Calmette–Guerin.
Muscle-invasive Nonmetastatic Bladder Cancer
Nivolumab may be considered an adjuvant therapy for patients who received cisplatin-based neoadjuvant therapy and for whom pathology after cystectomy demonstrates T3, T4, or node-positive disease, based on results of a recent phase 3 double-blind, randomized controlled trial published in The NEJM.
Locally Advanced or Metastatic Bladder Cancer
Four checkpoint inhibitors are FDA-approved for advanced bladder cancer:
- Pembrolizumab is approved as first-line therapy for metastatic bladder cancer with the explicit restriction not to use it in the first line for patients eligible for platinum-containing chemotherapy, regardless of PD-L1 expression status
- Atezolizumab is approved only for patients with locally advanced or metastatic bladder cancer who are ineligible for platinum-based chemotherapy and have never received it
- Nivolumab and avelumab are approved for metastatic bladder cancer that is refractory to platinum-based therapy
Antibody–drug conjugates are the newest therapies for metastatic bladder cancer that is refractory to platinum chemotherapy and checkpoint inhibitor therapy. Enfortumab vedotin is FDA-approved in this setting, and sacituzumab govitecan showed efficacy in a phase 2 trial published in the Journal of Clinical Oncology.
Prostate Cancer
Sipuleucel-T, an autologous cancer vaccine, can be the initial therapy for asymptomatic or minimally symptomatic patients with metastatic castrate-resistant prostate cancer (CRPC) whose disease burden is lower and immune function is presumably more intact. It can also be given to patients who previously received chemotherapy or novel hormonal therapy, but not both.
Importantly, the benefit of sipuleucel-T can't be measured through testing because trials haven't demonstrated a decline in prostate-specific antigen or objective improvement in imaging.
Pembrolizumab has no indication in CRPC but is an option for patients with metastatic CRPC, prior docetaxel therapy, prior treatment with novel hormonal therapy and high tumor mutational burden.
Studies of ipilimumab monotherapy have had mixed results in CRPC. Still, a phase 2 trial in which it was combined with nivolumab showed promise for patients with metastatic CRPC who had previously received chemotherapy (published in Cancer Cell).
Other Urologic Cancers
Immune-based therapies have been studied in a small number of patients with testicular cancer, and no data are available about immunotherapy for penile cancer.
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