TY - JOUR
T1 - Discontinuation of pembrolizumab for advanced urothelial carcinoma without disease progression
T2 - Nationwide cohort study
AU - Ito, Katsuhiro
AU - Kita, Yuki
AU - Yokomizo, Akira
AU - Miki, Jun
AU - Yoshio, Yuko
AU - Matsumoto, Hiroaki
AU - Segawa, Takehiko
AU - Karashima, Takashi
AU - Nishiyama, Naotaka
AU - Imai, Kazuto
AU - Suekane, Shigetaka
AU - Nagasawa, Seiji
AU - Higashi, Shin
AU - Nishiyama, Hiroyuki
AU - Kitamura, Hiroshi
AU - Kobayashi, Takashi
N1 - Publisher Copyright:
© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2023/2
Y1 - 2023/2
N2 - Pembrolizumab, an anti-programmed death 1 monoclonal antibody, has revolutionized the treatment of metastatic urothelial carcinoma. However, the optimal treatment duration for treatment responders has not been established. To address this, we retrospectively assess the treatment outcomes and duration of pembrolizumab for patients whose best response was complete response (CR) or partial response (PR) in a Japanese nationwide cohort of platinum-refractory metastatic urothelial carcinoma. Of 203 patients whose best response was CR or PR, 83 patients discontinued pembrolizumab before progression. The median pembrolizumab treatment duration was 6.9 months. The 2-year relapse-free survival (RFS), treatment-free survival, and OS rates after discontinuation were 49.0%, 57.4%, and 74.5%, respectively. CR, higher hemoglobin levels, and a better Eastern Cooperative Oncology Group performance status at the time of discontinuation were associated with significantly better RFS. Pembrolizumab was re-administered to 12 patients. Pembrolizumab re-challenge resulted in CR, PR, stable disease, and progressive disease in six, three, two, and one patient, respectively. Propensity score-matched landmark analysis revealed no significant OS difference between patients who continued or discontinued pembrolizumab at 6, 12, and 18 months (p = 0.91, 0.99, and 0.25, respectively). Our findings demonstrated that patients with objective responses had favorable survival outcomes and suggested that pembrolizumab could be discontinued safely in this population. This study should drive further efforts to optimize the treatment duration for pembrolizumab responders.
AB - Pembrolizumab, an anti-programmed death 1 monoclonal antibody, has revolutionized the treatment of metastatic urothelial carcinoma. However, the optimal treatment duration for treatment responders has not been established. To address this, we retrospectively assess the treatment outcomes and duration of pembrolizumab for patients whose best response was complete response (CR) or partial response (PR) in a Japanese nationwide cohort of platinum-refractory metastatic urothelial carcinoma. Of 203 patients whose best response was CR or PR, 83 patients discontinued pembrolizumab before progression. The median pembrolizumab treatment duration was 6.9 months. The 2-year relapse-free survival (RFS), treatment-free survival, and OS rates after discontinuation were 49.0%, 57.4%, and 74.5%, respectively. CR, higher hemoglobin levels, and a better Eastern Cooperative Oncology Group performance status at the time of discontinuation were associated with significantly better RFS. Pembrolizumab was re-administered to 12 patients. Pembrolizumab re-challenge resulted in CR, PR, stable disease, and progressive disease in six, three, two, and one patient, respectively. Propensity score-matched landmark analysis revealed no significant OS difference between patients who continued or discontinued pembrolizumab at 6, 12, and 18 months (p = 0.91, 0.99, and 0.25, respectively). Our findings demonstrated that patients with objective responses had favorable survival outcomes and suggested that pembrolizumab could be discontinued safely in this population. This study should drive further efforts to optimize the treatment duration for pembrolizumab responders.
KW - carcinoma, transitional cell
KW - duration of therapy
KW - immune checkpoint inhibitors
KW - immunotherapy
KW - pembrolizumab
UR - http://www.scopus.com/inward/record.url?scp=85134476870&partnerID=8YFLogxK
U2 - 10.1002/cam4.5057
DO - 10.1002/cam4.5057
M3 - 学術論文
C2 - 35864744
AN - SCOPUS:85134476870
SN - 2045-7634
VL - 12
SP - 2325
EP - 2332
JO - Cancer Medicine
JF - Cancer Medicine
IS - 3
ER -