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Clinical benefit of continuing pembrolizumab treatment beyond progression in patients with metastatic urothelial carcinoma

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Abstract

Background

There has been no clinical evidence to justify continued pembrolizumab therapy beyond progression in patients with metastatic urothelial carcinoma (UC).

Materials and methods

We conducted a multicenter retrospective study evaluating the clinical efficacy of continued use of pembrolizumab beyond progression in patients with metastatic UC. Data from 51 patients with metastatic UC, who developed progression during second-line pembrolizumab therapy, were analyzed. Progression was defined based on the Immunotherapy Response Evaluation Criteria in Solid Tumors. The outcome was overall survival (OS). The association between continued treatment, OS, and the risk of all-cause mortality was tested using log-rank test, conventional and time-dependent Cox regression models.

Results

No significant difference in patient characteristics was noted between patients continuing pembrolizumab beyond progression (N = 21) and those discontinuing pembrolizumab (N = 30). Median OS was significantly longer in the continuation group (17.8 vs. 8.8 months; P = 0.038). A multivariable conventional Cox regression model identified continued pembrolizumab administration as a significant independent prognostic factor of all-cause mortality (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.05–0.90, P = 0.036), irrespective of the time from treatment initiation to progression and concurrent clinical progression. Further, longer duration of pembrolizumab treatment beyond progression was independently associated with a reduced risk of all-cause mortality in a multivariable time-dependent Cox regression model, when used as a time-dependent variable (HR: 0.07, 95% CI: 0.01–0.45, P = 0.006).

Conclusions

Continued pembrolizumab administration beyond progression might be beneficial in patients with metastatic UC who were clinically stable.

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Abbreviations

CI:

Confidence interval

ECOG:

Eastern Cooperative Oncology Group

HR:

Hazard ratio

iCPD:

Immune-confirmed progressive disease

IQR:

Interquartile range

iSD:

Immune stable disease

iUPD:

Immune-unconfirmed progressive disease

LN:

Lymph node

OS:

Overall survival

PD:

Progressive disease

PD-1:

Programmed death -1

RECIST:

Response Evaluation Criteria in Solid Tumors

UC:

Urothelial carcinoma

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Authors and Affiliations

  1. Department of Urology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan

    Wataru Fukuokaya, Takahiro Kimura, Takafumi Yanagisawa, Shoji Kimura, Shunsuke Tsuzuki, Yuhei Koike, Yuya Iwamoto, Yuki Enei, Masatoshi Tanaka, Fumihiko Urabe, Hajime Onuma, Mariko Honda, Jun Miki, Hirokazu Abe & Shin Egawa

  2. Department of Urology, Kameda Medical Center, 929 Higashi-cho, Kamogawa City, Chiba, 296-8602, Japan

    Yuhei Koike & Hirokazu Abe

  3. Department of Medical Oncology, Kameda Medical Center, 929 Higashi-cho, Kamogawa City, Chiba, 296-8602, Japan

    Yu Oyama

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  1. Wataru Fukuokaya
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Contributions

Conception and design: WF, TK, SE. Collection and assembly of data: WF, TY, ST, YK, YI, YE, MT, FU, HO, MH. Data analysis and interpretation: WF, TK, TY, SK, FU, JM, YO, HA. Manuscript writing: all authors. Final approval of manuscript: all authors.

Corresponding author

Correspondence to Wataru Fukuokaya.

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Conflict of interest

Shin Egawa is a paid consultant/advisor to Takeda, Astellas, AstraZeneca, Sanofi, Janssen, and Pfizer. The other authors declare no conflict of interest associated with this manuscript.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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Fukuokaya, W., Kimura, T., Yanagisawa, T. et al. Clinical benefit of continuing pembrolizumab treatment beyond progression in patients with metastatic urothelial carcinoma. Cancer Immunol Immunother 71, 229–236 (2022). https://doi.org/10.1007/s00262-021-02980-x

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  • DOI: https://doi.org/10.1007/s00262-021-02980-x

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