Perspectives on the future of urothelial carcinoma therapy: chemotherapy and beyond

TY - JOUR

T1 - Perspectives on the future of urothelial carcinoma therapy: chemotherapy and beyond

AU - Bianchi, Alberto

AU - von Deimling, Markus

AU - Pallauf, Maximilian

AU - Yanagisawa, Takafumi

AU - Kawada, Tatsushi

AU - Mostafaei, Hadi

AU - Quhal, Fahad

AU - Laukhtina, Ekaterina

AU - Rajwa, Pawel

AU - Majdoub, Muhammad

AU - Sari Motlagh, Reza

AU - Pradère, Benjamin

AU - Karakiewicz, Pierre I

AU - Cerruto, Maria Angela

AU - Antonelli, Alessandro

AU - Shariat, Shahrokh F

PY - 2023/2

Y1 - 2023/2

N2 - INTRODUCTION: Despite recent developments in the landscape of urothelial carcinoma (UC) treatment, platinum combination chemotherapy still remains a milestone. Recently immunotherapeutic agents have gained ever-growing attractivity, particularly in the metastatic setting. Novel chemotherapeutic strategies and agents, such as antibody-drug conjugates (ADCs), and powerful combination regimens have been developed to overcome the resistance of most UC to current therapies.AREAS COVERED: Herein, we review the current standard-of-care chemotherapy, the development of ADCs, the rationale for combining therapy regimens with chemotherapy in current trials, and future directions in UC management.EXPERT OPINION: Immunotherapy has prompted a revolution in the treatment paradigm of UC. However, only a few patients experience a long-term response when treated with single-agent immunotherapies. Combination treatments are necessary to bypass resistance mechanisms and broaden the clinical utility of current options. Current evidence supports the intensification of standard-of-care chemotherapy with maintenance immunotherapy. However, the optimal sequence, combination, and duration must be determined to achieve individual longevity with acceptable health-related quality of life. In that regard, ADCs appear as a promising alternative for single and combination strategies in UC, as they specifically target the tumor cells, thereby, theoretically improving treatment efficacy and avoiding extensive off-target toxicities.

AB - INTRODUCTION: Despite recent developments in the landscape of urothelial carcinoma (UC) treatment, platinum combination chemotherapy still remains a milestone. Recently immunotherapeutic agents have gained ever-growing attractivity, particularly in the metastatic setting. Novel chemotherapeutic strategies and agents, such as antibody-drug conjugates (ADCs), and powerful combination regimens have been developed to overcome the resistance of most UC to current therapies.AREAS COVERED: Herein, we review the current standard-of-care chemotherapy, the development of ADCs, the rationale for combining therapy regimens with chemotherapy in current trials, and future directions in UC management.EXPERT OPINION: Immunotherapy has prompted a revolution in the treatment paradigm of UC. However, only a few patients experience a long-term response when treated with single-agent immunotherapies. Combination treatments are necessary to bypass resistance mechanisms and broaden the clinical utility of current options. Current evidence supports the intensification of standard-of-care chemotherapy with maintenance immunotherapy. However, the optimal sequence, combination, and duration must be determined to achieve individual longevity with acceptable health-related quality of life. In that regard, ADCs appear as a promising alternative for single and combination strategies in UC, as they specifically target the tumor cells, thereby, theoretically improving treatment efficacy and avoiding extensive off-target toxicities.

KW - Antineoplastic Agents/therapeutic use

KW - Carcinoma, Transitional Cell/drug therapy

KW - Humans

KW - Immunotherapy

KW - Quality of Life

KW - Urinary Bladder Neoplasms/drug therapy

U2 - 10.1080/14656566.2022.2150966

DO - 10.1080/14656566.2022.2150966

M3 - SCORING: Review article

C2 - 36440477

VL - 24

SP - 177

EP - 195

JO - EXPERT OPIN PHARMACO

JF - EXPERT OPIN PHARMACO

SN - 1465-6566

IS - 2

ER -