First-line Immune Checkpoint Inhibitor Combinations in Metastatic Renal Cell Carcinoma: Where Are We Going, Where Have We Been?

Adashek, Jacob J.; Breunig, Joshua J.; Posadas, Edwin M.; Bhowmick, Neil A.; Ellis, Leigh; Freedland, Stephen J.; Kim, Hyung L.; Figlin, Robert A.; Gong, Jun

doi:10.1007/s40265-022-01683-6

Cited by 5 publications

(2 citation statements)

References 91 publications

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“…Within 8 years of the TKI era, immune checkpoint inhibitors (ICI) became the next class of agents with proven efficacy in mRCC. 5 Soon thereafter, it was observed that combination approaches, whether with ICIICI or TKI/ICI, may be administered safely and with superior outcomes to TKIs alone. 6 , 7 The rapid development of these novel agents and combination therapies created a level of uncertainty in the treatment paradigm that has yet to be reconciled in the literature or evidence-based guidelines.…”

Section: Introductionmentioning

confidence: 99%

Comparative Effectiveness of Front-Line Ipilimumab and Nivolumab or Axitinib and Pembrolizumab in Metastatic Clear Cell Renal Cell Carcinoma

et al. 2022

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Background Treatment of metastatic renal cell carcinoma (mRCC) is rapidly evolving with new combination therapies demonstrating improved response rates and survival. There are no head-to-head prospective trials comparing an immunotherapy doublet with an immunotherapy/tyrosine-kinase inhibitor-based combination. We compare real-world outcomes in patients treated with axitinib/pembrolizumab (axi/pembro) or ipilimumab/nivolumab (ipi/nivo). The primary endpoints were overall-survival (OS) and real-world progression-free survival (rwPFS). Patients and Methods We used a de-identified database to select patients diagnosed with clear cell mRCC and treated with front-line axi/pembro or ipi/nivo from 2018 to 2022. Analyses are adjusted using propensity score-based inverse probability of treatment weighting, balancing age, gender, insurance, race, IMDC risk, and nephrectomy status. We compared survival by treatment groups using weighted and unweighted Kaplan–Meier curves with log-rank tests and weighted Cox proportional hazards regressions. Results We included a total of 1506 patients with mRCC who received frontline axi/pembro (n = 547) or ipi/nivo (n = 959). Median follow-up time was 20.0 months (range: 0.2-47.6). Baseline demographics were similar between the 2 cohorts. Adjusted median OS for the full population was 28.9 months for axi/pembro and was 24.3 months for ipi/nivo (P = .09). Twenty-four-month survival was 53.8% for axi/pembro treated patients and 50.2% for ipi/nivo treated patients. rwPFS was 10.6 months for axi/pembro treated patients and 6.9 months for ipi/nivo treated patients. Treatment with axi/pembro conferred improved survival in the IMDC favorable risk strata, with no significant difference in survival observed within the full cohort. Conclusions In this retrospective, real-world study of patients treated with front-line combination therapy, patients with IMDC favorable risk disease had better survival when treated with axi/pembro compared to ipi/nivo. However, survival for the entire population and the 24-month median overall survival were not statistically different between treatment groups. Longer follow-up is necessary to discern any emerging significant differences.

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Section: Introductionmentioning

confidence: 99%

Comparative Effectiveness of Front-Line Ipilimumab and Nivolumab or Axitinib and Pembrolizumab in Metastatic Clear Cell Renal Cell Carcinoma

et al. 2022

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“…Efforts then quickly turned toward combination strategies, all applied in the first line and in lieu of TKI monotherapy. 2 These include pairings of not only programmed death 1 (PD1)directed CPI plus TKI [3][4][5] but also the CPI doublet of nivolumab plus the cytotoxic T-cell lymphocyte-4 (CTLA-4) inhibitor ipilimumab. 6 Such first-line combinations were developed without formally extending CPI monotherapy into the frontline first, and the pivotal trials compared the various doublets to single-agent TKI as the reference standard.…”

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confidence: 99%

Up-front Nivolumab With or Without Salvage Ipilimumab Across International Metastatic Database Consortium Risk Groups in Metastatic Clear Cell Renal Cell Carcinoma

Voss

2022

JCO

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Perioperative Complications and Oncologic Outcomes of Nephrectomy Following Immune Checkpoint Inhibitor Therapy: A Multicenter Collaborative Study

Yip¹,

Ghoreifi²,

Gerald³

et al. 2023

European Urology Oncology

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First-line Immune Checkpoint Inhibitor Combinations in Metastatic Renal Cell Carcinoma: Where Are We Going, Where Have We Been?

Cited by 5 publications

References 91 publications

Comparative Effectiveness of Front-Line Ipilimumab and Nivolumab or Axitinib and Pembrolizumab in Metastatic Clear Cell Renal Cell Carcinoma

Comparative Effectiveness of Front-Line Ipilimumab and Nivolumab or Axitinib and Pembrolizumab in Metastatic Clear Cell Renal Cell Carcinoma

Up-front Nivolumab With or Without Salvage Ipilimumab Across International Metastatic Database Consortium Risk Groups in Metastatic Clear Cell Renal Cell Carcinoma

Perioperative Complications and Oncologic Outcomes of Nephrectomy Following Immune Checkpoint Inhibitor Therapy: A Multicenter Collaborative Study

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