A Retrospective Study of First-Line Therapy Involving Immune Checkpoint Inhibitors in Patients With Poor Risk Metastatic Renal Cell Carcinoma

Hyunji Jo; Joohyun Hong; Hongsik Kim; Hye Ryeon Kim; Ghee Young Kwon; Kyung A Kang; Sung Yoon Park; Chan Kyo Kim; Byung Kwan Park; Jae Hoon Chung; Wan Song; Minyong Kang; Hyun Hwan Sung; Hwang Gyun Jeon; Byong Chang Jeong; Seong Il Seo; Seong Soo Jeon; Hyun Moo Lee; Se Hoon Park

doi:10.3389/fonc.2022.874385

A Retrospective Study of First-Line Therapy Involving Immune Checkpoint Inhibitors in Patients With Poor Risk Metastatic Renal Cell Carcinoma

Front Oncol. 2022 Apr 28:12:874385. doi: 10.3389/fonc.2022.874385. eCollection 2022.

Authors

Hyunji Jo¹, Joohyun Hong¹, Hongsik Kim¹, Hye Ryeon Kim¹, Ghee Young Kwon², Kyung A Kang³, Sung Yoon Park³, Chan Kyo Kim³, Byung Kwan Park³, Jae Hoon Chung⁴, Wan Song⁴, Minyong Kang⁴, Hyun Hwan Sung⁴, Hwang Gyun Jeon⁴, Byong Chang Jeong⁴, Seong Il Seo⁴, Seong Soo Jeon⁴, Hyun Moo Lee⁴, Se Hoon Park¹

Affiliations

¹ Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
² Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
³ Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁴ Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Abstract

Purpose: Patients with International Metastatic RCC Database Consortium (IMDC) poor risk metastatic renal cell carcinoma (mRCC) rarely respond to first-line tyrosine kinase inhibitors (TKIs) including sunitinib, and carries a very poor prognosis. In recent years, combination therapy involving immune checkpoint inhibitors (ICIs) have demonstrated superior efficacy to sunitinib in poor risk disease.

Materials and methods: In a retrospective study using a cancer chemotherapy registry, 206 consecutive patients with mRCC in the first-line setting were identified between Oct 2019 and Dec 2020. Sixty-one patients had a poor risk mRCC, and were treated with TKI monotherapy (n=36), nivolumab plus ipilimumab (n=16), or pembrolizumab plus axitinib (n=9). Endpoints included overall survival (OS), progression-free survival (PFS), response rate (RR), and safety.

Results: Patients' median age was 61 years and the median number of risk factors was 3 (range, 3-5). During a median 23.0 months of follow-up, the median OS was 24.3 months with ICI-based combinations and 14.8 months with TKI monotherapy, and the median PFS periods were 9.3 months and 3.4 months, respectively. An objective response occurred in 60% of the patients receiving ICI-based combinations and in 19% of those receiving TKI monotherapy (P=0.001). In the multivariate regression model, number of IMDC risk factors and the ICI-based combination therapy were independent prognostic factors for PFS. All-causality grade 3 or 4 adverse events were 44% for ICI-based combinations and 50% for TKI monotherapy.

Conclusions: Among patients with poor risk mRCC, first-line ICI-based therapy showed significantly longer OS and PFS, as well as a higher RR, than TKI monotherapy.

Keywords: IMDC poor-risk; immune checkpoint inhibitors; immunotherapy; overall survival; renal cell carcinoma; sunitinib.