Hiroki Ishihara1, Tsunenori Kondo2, Toshio Takagi1, Hidekazu Tachibana3, Hironori Fukuda1, Kazuhiko Yoshida1, Junpei Iizuka1, Hirohito Kobayashi1, Kazunari Tanabe1. 1. Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. 2. Department of Urology, Tokyo Women's Medical University Medical Center East, 2-1-10 Nishiogu, Arakawa-ku, Tokyo, 116-8567, Japan. kondo.tsunenori@twmu.ac.jp. 3. Department of Urology, Tokyo Women's Medical University Medical Center East, 2-1-10 Nishiogu, Arakawa-ku, Tokyo, 116-8567, Japan.
Abstract
BACKGROUND: Investigations on rapid disease progression in patients with urologic malignancies treated with immune checkpoint inhibitors are currently lacking. OBJECTIVE: The objective of this study was to assess cases of rapid disease progression/immediate development of progressive disease (immediate PD) in patients with pretreated metastatic renal cell carcinoma (mRCC) treated with nivolumab. PATIENTS AND METHODS: Forty patients were retrospectively evaluated. Immediate PD within the initial two cycles of nivolumab therapy was clinically or objectively diagnosed. Clinical diagnosis was defined as an acceleration of symptoms directly caused by tumor growth or systematic worsening of the general condition, such as cachexia. Objective diagnosis was based on imaging evaluation using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). RESULTS: Seven patients (17.5%) developed immediate PD. For these patients, the median time from the initiation of nivolumab treatment to PD was 14 days; all seven patients subsequently died from the cancer. Progression-free survival (0.66 vs. 10.5 months; p < 0.0001) and overall survival (1.41 months vs. not reached; p < 0.0001) were significantly shorter in patients with immediate PD than in those without immediate PD. Further, female sex (p = 0.0434), poor Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score (p = 0.0263), and shorter prior-line time to progression (p = 0.0218) were associated with immediate PD. CONCLUSIONS: The development of immediate PD in mRCC patients treated with nivolumab can severely worsen patient prognosis. Sex, MSKCC score, and prior-line time to progression may be involved in the development of immediate PD. Prospective studies are needed to further assess these findings.
BACKGROUND: Investigations on rapid disease progression in patients with urologic malignancies treated with immune checkpoint inhibitors are currently lacking. OBJECTIVE: The objective of this study was to assess cases of rapid disease progression/immediate development of progressive disease (immediate PD) in patients with pretreated metastatic renal cell carcinoma (mRCC) treated with nivolumab. PATIENTS AND METHODS: Forty patients were retrospectively evaluated. Immediate PD within the initial two cycles of nivolumab therapy was clinically or objectively diagnosed. Clinical diagnosis was defined as an acceleration of symptoms directly caused by tumor growth or systematic worsening of the general condition, such as cachexia. Objective diagnosis was based on imaging evaluation using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). RESULTS: Seven patients (17.5%) developed immediate PD. For these patients, the median time from the initiation of nivolumab treatment to PD was 14 days; all seven patients subsequently died from the cancer. Progression-free survival (0.66 vs. 10.5 months; p < 0.0001) and overall survival (1.41 months vs. not reached; p < 0.0001) were significantly shorter in patients with immediate PD than in those without immediate PD. Further, female sex (p = 0.0434), poor Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score (p = 0.0263), and shorter prior-line time to progression (p = 0.0218) were associated with immediate PD. CONCLUSIONS: The development of immediate PD in mRCC patients treated with nivolumab can severely worsen patient prognosis. Sex, MSKCC score, and prior-line time to progression may be involved in the development of immediate PD. Prospective studies are needed to further assess these findings.
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