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26.06.2021 | Original Research Article

Prognostic Impact of Early Treatment Interruption of Nivolumab Plus Ipilimumab Due to Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma: A Multi-Institution Retrospective Study

verfasst von: Hiroki Ishihara, Yuki Nemoto, Kazutaka Nakamura, Takashi Ikeda, Hidekazu Tachibana, Hironori Fukuda, Kazuhiko Yoshida, Hirohito Kobayashi, Junpei Iizuka, Hiroaki Shimmura, Yasunobu Hashimoto, Toshio Takagi, Hideki Ishida, Tsunenori Kondo, Kazunari Tanabe

Erschienen in: Targeted Oncology | Ausgabe 4/2021

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Abstract

Background

It remains unclear how early treatment interruption of nivolumab plus ipilimumab due to immune-related adverse events affects the outcome of previously untreated metastatic renal cell carcinoma (mRCC).

Objective

To investigate the prognostic impact of the early interruption of nivolumab plus ipilimumab, used as first-line therapy for mRCC.

Patients and Methods

We retrospectively evaluated 59 intermediate- or poor-risk mRCC patients who received nivolumab plus ipilimumab as first-line therapy. Based on whether early treatment interruption was implemented within the initial four treatment cycles (i.e., 3 months) or not, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were compared. The prognostic association was further compared with that of 186 patients treated with tyrosine kinase inhibitors (TKIs) as first-line therapy.

Results

Twenty-three of the 59 patients (39%) experienced interruption of nivolumab plus ipilimumab therapy. The patients with interruption had longer PFS (p = 0.0055), similar OS (p = 0.366), and likely higher ORR (p = 0.0660) than those without interruption. Of the patients treated with TKIs, 60 of 186 (32%) experienced interruption, with shorter PFS (p = 0.0121), similar OS (p = 0.378), and similar ORR (p = 0.738) than those without interruption. In the 23 patients with nivolumab plus ipilimumab interruption, high-dose corticosteroids were administered in seven patients (30%). PFS (p = 0.638), OS (p = 0.968), or ORR (p = 0.760) did not differ based on corticosteroid administration.

Conclusions

Early treatment interruption, which exerted a negative effect for TKIs, was a preferable event for nivolumab plus ipilimumab when considering PFS. Furthermore, early administration of high-dose corticosteroids did not diminish the anti-tumor effect of nivolumab plus ipilimumab.

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Titel: Prognostic Impact of Early Treatment Interruption of Nivolumab Plus Ipilimumab Due to Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma: A Multi-Institution Retrospective Study
verfasst von: Hiroki Ishihara
Yuki Nemoto
Kazutaka Nakamura
Takashi Ikeda
Hidekazu Tachibana
Hironori Fukuda
Kazuhiko Yoshida
Hirohito Kobayashi
Junpei Iizuka
Hiroaki Shimmura
Yasunobu Hashimoto
Toshio Takagi
Hideki Ishida
Tsunenori Kondo
Kazunari Tanabe
Publikationsdatum: 26.06.2021
Verlag: Springer International Publishing
Erschienen in: Targeted Oncology / Ausgabe 4/2021
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-021-00825-2

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Prognostic Impact of Early Treatment Interruption of Nivolumab Plus Ipilimumab Due to Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma: A Multi-Institution Retrospective Study