Prognostic impact of first-line (1L) chemotherapy cycles in patients with metastatic urothelial carcinoma receiving avelumab 1L maintenance.
Authors: Katayama Satoshi , Kawada Tatsuhi , Kobayashi Keita , Watanabe Ryuta , Tohi Yoichiro , Yamamoto Shinkuro , Takamoto Atsushi , Shimizu Ryutaro , Daizumoto Kei , Nagami Taichi , Wada Koichiro , Furukawa Junya , Miura Noriyoshi , Morizane Shuichi , Inoue Keiji , Sugimoto Mikio , Shiraishi Koji , Araki Motoo 
Published: February 2025

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Background:
First-line chemotherapy with 4-6 cycles followed by avelumab 1L maintenance therapy is the standard of care in patients with metastatic urothelial carcinoma (mUC). However, a non-negligible number of patients received less than four cycles of chemotherapy due to adverse events, or pre-existing severe comorbidities in our daily practice. Thus, we examined the prognostic impact of the number of first-line chemotherapy cycles in mUC patients treated with avelumab.
Methods:
In this multi-institutional study, we collected data of 91 patients with mUC who received avelumab maintenance therapy following 1
st
-line chemotherapy. Patients were divided into those who received less than four cycles and those more than four cycles. Kaplan-Meier curve and Cox regression model were used to assess the association of chemotherapy cycles with overall (OS), cancer-specific (CSS), and progression-free survival (PFS). Logistic regression analyses were used to assess factors predicting initial progressive disease (PD).
Results:
Of the patients, 17 (19%) underwent less than four cycles of chemotherapy. Baseline characteristics, including chemotherapy regimen and best response to 1L chemotherapy, were comparable between the groups. Kaplan-Meier curve showed that patients receiving less than four cycles of chemotherapy were significantly associated with shorter OS (
p
=0.032). On multivariable analyses controlling for the effects of confounding factors, the number of cycles (< 4) remained associated with worse OS, CSS, and PFS (HR 2.83; 95%CI 1.32-6.08; p=0.008, HR 3.37; 95%CI 1.52-7.47; p=0.003, and HR 2.11; 95%CI 1.09-4.07; p=0.03, respectively). In addition, the number of cycles was associated with an increased risk of initial PD (OR 3.26; 95%CI 1.08-9.79;
p
=0.035) for avelumab maintenance therapy.
Conclusions:
The inadequate number of 1L chemotherapy cycles was associated with poor survival outcomes and was at an increased risk of initial PD in patients receiving avelumab maintenance therapy. More than four cycles of 1L chemotherapy should be given to ensure the efficacy of avelumab maintenance therapy in patients with mUC.

OS

CSS

PFS

Predicting PD

Multivariable

Multivariable

Multivariable

Multivariate

HR

(95% CI)

P
value

HR

(95% CI)

P
value

HR

(95% CI)

P
value

OR

(95% CI)

P
value

Age (ref. < 70)

1.2
0.54-2.70
0.66

1.09
0.48-2.49
0.84

1.21
0.46-3.23
0.70

1.54
0.48-4.96
0.47

ECOG-PS≥2 (ref.≤1)

7.01
1.67-29.9

0.008

10.3
2.27-46.9

0.003

2.63
0.29-23.7
0.39

1.07
0.10-11.3
0.96

Severe AE (ref. < G3)

0.96
0.47-1.94
0.9

0.80
0.38-1.66
0.55

1.86
0.83-4.15
0.13

Visceral metastasis

2.20
1.05-4.60

0.037

2.43
1.11-5.29

0.026

2.23
1.01-4.91

0.046

eGFR (ref. < 60)

0.81
0.34-1.89
0.62

0.70
0.28-1.75
0.44

0.62
0.22-1.77
0.38

1st-line chemotherapy cycle (ref. ≥ 4)

2.83
1.32-6.08

0.008

3.37
1.52-7.47

0.003

2.11
1.09-4.07

0.03

3.26
1.08-9.79

0.035