Immune checkpoint-inhibitor (ICI)-based therapy is the standard of care for first-line treatment of metastatic renal cell carcinoma (mRCC). It is unclear whether prior removal of the primary tumor influences the efficacy of these treatments. We performed a systematic review and meta-analysis of studies of first-line ICI in mRCC to determine whether the efficacy of ICI-therapy, compared to sunitinib, is altered based on receipt of prior nephrectomy.
We systematically reviewed studies indexed in MEDLINE (PubMed), Embase, and Scopus and conference abstracts from relevant medical societies as of August 2020 to identify randomized clinical trials assessing first-line immunotherapy-based regimes in mRCC. Studies were included if overall survival (OS) and progression-free survival (PFS) outcomes were reported with data stratified by nephrectomy status. We pooled hazard ratios (HRs) stratified by nephrectomy status and performed random effects meta-analysis to assess the null hypothesis of no difference in the survival advantage of immunotherapy-based regimes based on nephrectomy status, while accounting for study level correlations.
Among 6 randomized clinical trials involving 5,121 patients, 3,968 (77%) had undergone prior nephrectomy. We found an overall survival benefit for immunotherapy-based regimes, compared to sunitinib, among both patients who had undergone nephrectomy (HR 0.75, 95% CI 0.63 -0.88) and those who had not (HR 0.74, 95% CI 0.59 -0.92), without evidence of difference based on nephrectomy history (P = 0.70; I2 = 36%). Results assessing PFS were similar (P = 0.45, I2 = 0%).
These clinical data suggest that prior nephrectomy does not affect the efficacy of ICI-based regimens in mRCC relative to sunitinib.
Urologic oncology. 2021 Oct 21 [Epub ahead of print]
Raj Satkunasivam, Jonathan Ca Guzman, Zachary Klaassen, Mary E Hall, Amy N Luckenbaugh, Kelvin Lim, Aaron A Laviana, Antonio P DeRosa, Kathryn E Beckermann, Brian Rini, Christopher Jd Wallis
Department of Urology and Center for Outcomes Research, Houston Methodist Hospital, Houston, Taxas. Electronic address: ., Department of Urology and Center for Outcomes Research, Houston Methodist Hospital, Houston, Taxas., Department of Surgery, Division of Urology, Medical College of Georgia at Augusta University, Augusta, Georgia; Georgia Cancer Center - Augusta University, Augusta, Georgia., Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee., Department of Surgery & Perioperative Medicine, The University of Texas at Austin Dell Medical School, Austin, Taxas., Meyer Cancer Center's Office of Community Outreach and Engagement, Weill Cornell Medicine, New York, New York., Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.