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Urology News and Education Resource
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Monday, 13 May 2024 |
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First-line Therapy Options for Metastatic Renal Cell Carcinoma
Tian Zhang, MD
Tian Zhang and Monty Pal review first-line therapy options for metastatic renal cell carcinoma (mRCC), including immunotherapy- based ipilimumab, nivolumab, pembrolizumab, axitinib, as well as avelumab/axitinib combinations and cabozantinib monotherapy. Tian continues focusing on achieving a complete response rate, and treating intermediate, poor-risk disease where she describes an exciting new front-line trial in the Alliance Cooperative Group now activated throughout the National Clinical Trials Network supported by the NCI.
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The Role of Cytoreductive Nephrectomy in Patients with Metastatic Renal Cell Carcinoma
Neeraj Agarwal, MD
Neeraj Agarwal discusses the recent update to the CARMENA trial which was presented at ASCO 2019. The Phase 3 non-inferiority CARMENA trial comparing sunitinib versus nephrectomy followed by sunitinib established that patients could avoid nephrectomy without compromising survival.
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Newly Approved Treatment Options for the Management of Metastatic Kidney Cancer- Lauren Harshman and Toni Choueiri
Lauren C. Harshman, MD
Lauren Harshman Alicia Morgans, and Toni Choueiri discuss combination therapy for the management of metastatic kidney cancer with the recent approval of pembrolizumab plus axitinib. They discuss the safety profiles of each of the combination approaches taking into consideration the dual IO approach versus the combination of IO plus VEGF blockade. The discussion leads to the ongoing research evaluating whether these drugs can be sequenced based on the response in the ongoing OMNIVORE trial.
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Frontline Data from Keynote 426
Sandy Srinivas, MD
Sandy Srinivas discusses the frontline data from the KEYNOTE 426 trial comparing pembrolizumab plus axitinib to sunitinib monotherapy in clear cell kidney cancer. 800 patients were randomized and the combination demonstrated benefit across all three outcomes measured including response rates, PFS and overall survival.
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Pembrolizumab Plus Axitinib versus Sunitinib as First-Line Therapy for mRCC: Outcomes in the Combined IMDC Intermediate/Poor Risk and Sarcomatoid Subgroups of the Phase 3 KEYNOTE-426 Study
In KEYNOTE-426, pembrolizumab plus axitinib significantly improved overall survival, progression-free survival, and objective response rate vs sunitinib. This combination therapy also had manageable toxicity as first-line therapy for mRCC. Furthermore, the pembrolizumab plus axitinib benefit was observed across all IMDC risk groups and regardless of PD-L1 expression. Brian Rini and KEYNOTE-426 investigators presented outcomes for the combined intermediate/poor risk group and for patients with sarcomatoid features.
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CheckMate 214 Post-Hoc Analyses of Nivolumab plus Ipilimumab or Sunitinib in IMDC Intermediate/Poor-Risk Patients with Previously Untreated Advanced Renal Cell Carcinoma with Sarcomatoid Features
The landscape of systemic therapy for metastatic renal cell carcinoma is rapidly changing. Beyond the addition of immune checkpoint inhibitor combinations (nivo/ipi), additional tyrosine kinase inhibitors (TKIs) (cabozantinib), there are now combination therapies that are demonstrating excellent responses rates in the first line. The recent data from KEYNOTE‑426 has led to the approval of axinitib/pemrbolizumab in the first line for mRCC, and as can be expected from this combination, it seems to have efficacy for good, intermediate and poor risk patients.
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Evolving Front-Line Therapy in Metastatic Renal Cell Carcinoma
Rana McKay, MD, provided a discussion following the presentation of three renal cell carcinoma abstracts. Pembrolizumab plus axitinib versus sunitinib as first-line therapy for mRCC. A pilot randomized study evaluating nivo or nivo + bevacizumab or nivo + ipi in patients with mRCC eligible for CN, metastasectomy or post-treatment biopsy, and pazopanib vs pbo in patients with mRCC who have no evidence of disease following metastasectomy.
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Nivolumab With or Without Bevacizumab or Ipilimumab Before Surgery in Treating Patients With Metastatic Kidney Cancer That Can Be Removed by Surgery
Cytoreductive surgery, including cytoreductive nephrectomy and metastasectomy, provides clinical benefits to patients with mRCC. However, cytoreductive surgery has not been evaluated in the setting of immune checkpoint therapy. At the ASCO 2019 kidney cancer session, Jianjun Gao, MD, and colleagues presented results of their pilot study evaluating nivolumab or nivolumab + bevacizumab or nivo + ipi in patients with mRCC eligible for cytoreductive nephrectomy, metastasectomy or post-treatment biopsy.
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Challenging Established Frontline Therapies in Renal Cancer
Dr. Laurence Albiges discussed the challenges faced by established frontline therapies in renal cancer. Highlighting the Checkmate 214 trial, the comparison of sunitinib to Nivolumab + ipilimumab, IMmotion 151, and JAVELIN renal. The new combination of ICI + VEGF inhibitor setting a new bar, with an objective response rate around 55-58%
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