Global BulletinAll NewsFDA Approval AlertWomen in Oncology
Expert InterviewsAround the PracticeBetween the LinesFace OffFrom All AnglesMeeting of the MindsOncViewPodcastsTraining AcademyTreatment Algorithms with the Oncology BrothersVideos
Conferences
All JournalsEditorial BoardFor AuthorsYear in Review
Frontline ForumSatellite Sessions
CME/CE
Awareness MonthInteractive ToolsNurse Practitioners/Physician's AssistantsPartnersSponsoredSponsored Media
Career CenterSubscribe
Adverse Effects
Brain Cancer
Breast CancerBreast CancerBreast Cancer
Gastrointestinal CancerGastrointestinal CancerGastrointestinal CancerGastrointestinal CancerGastrointestinal CancerGastrointestinal Cancer
Genitourinary CancersGenitourinary CancersGenitourinary CancersGenitourinary Cancers
Gynecologic CancersGynecologic CancersGynecologic CancersGynecologic Cancers
Head & Neck Cancer
Hematologic OncologyHematologic OncologyHematologic OncologyHematologic Oncology
InfectionInfection
Leukemia
Lung CancerLung CancerLung Cancer
Lymphoma
Neuroendocrine Tumors
Oncology
Pediatric Cancers
Radiation Oncology
Sarcoma
Screening
Skin Cancer & Melanoma
Surgery
Thyroid Cancer
Spotlight -
  • Radiation Oncology
  • Surgery
Adverse Effects
Brain Cancer
Breast CancerBreast CancerBreast Cancer
Gastrointestinal CancerGastrointestinal CancerGastrointestinal CancerGastrointestinal CancerGastrointestinal CancerGastrointestinal Cancer
Genitourinary CancersGenitourinary CancersGenitourinary CancersGenitourinary Cancers
Gynecologic CancersGynecologic CancersGynecologic CancersGynecologic Cancers
Head & Neck Cancer
Hematologic OncologyHematologic OncologyHematologic OncologyHematologic Oncology
InfectionInfection
Leukemia
Lung CancerLung CancerLung Cancer
Lymphoma
Neuroendocrine Tumors
Oncology
Pediatric Cancers
Radiation Oncology
Sarcoma
Screening
Skin Cancer & Melanoma
Surgery
Thyroid Cancer
    • Conferences
    • CME/CE
    • Career Center
    • Subscribe

Your AI-Trained Oncology Knowledge Connection!

scout
Advertisement

Navigating an Optimal Treatment Course for Advanced Kidney Cancer

June 20, 2021
By Benjamin A. Teply, MD
Publication
Article
OncologyONCOLOGY Vol 35, Issue 6
Pages: 308-309

Benjamin A. Teply, MD, considers the optimal treatment of renal cell carcinoma in a peer perspective accompanying an article by Tiffany Y. Shaw, MD, and colleagues.

Teply is from the Division of Hematology/Oncology in the Department of Internal Medicine at the University of Nebraska Medical Center in Omaha, NE.

Teply is from the Division of Hematology/Oncology in the Department of Internal Medicine at the University of Nebraska Medical Center in Omaha, NE.

The authors of the accompanying article review the rapidly evolving treatment paradigms for renal cell carcinoma in both the first- and second-line settings. A remarkable sea change has occurred over the past 3-plus years, as the results of 5 separate positive phase 3 studies have demonstrated superiority of immunotherapy-containing regimens over monotherapy with the anti-VEGF tyrosine kinase inhibitor (TKI) sunitinib (Sutent) in the first-line setting. As a result, it is now the standard of care that most patients with advanced kidney cancer receive either combination immunotherapy or immunotherapy-TKI combinations. In fact, every eligible patient with advanced kidney cancer should receive immune checkpoint blockade during their treatment course, with the hope of deriving durable responses.

Nonetheless, the first question with regard to treatment sequencing is whether all patients with advanced/metastatic kidney cancer require up-front immunotherapy, rather than second- or later-line immunotherapy. Let us first examine the data for International Metastatic RCC Database Consortium (IMDC) intermediate- and poor-risk disease. In this scenario, my answer is a resounding yes. Four FDA-approved options—axitinib (Inlyta) plus pembrolizumab (Keytruda),1 lenvatinib (Lenvima) plus pembrolizumab,2 cabozantinib (Cabometyx) plus nivolumab (Opdivo),3 and ipilimumab (Yervoy) plus nivolumab4—demonstrated significantly improved overall survival (OS) in these cohorts. These regimens are all included as preferred options with category 1 evidence in the National Comprehensive Cancer Network guidelines. Axitinib plus avelumab (Bavencio)5 is another option, with data showing significantly improved progression-free survival. In sum, the data strongly support first-line utilization of anti–PD-1 therapy for intermediate- or poor-risk disease.

However, is the same true for patients presenting with IMDC favorable-risk disease? The answer is less straightforward. The data for up-front immunotherapy are suggestive of survival benefit, but nearly all these patients will be able to receive a second-line therapy incorporating anti–PD-1 therapy, given the relatively indolent course of favorable-risk disease. Furthermore, with longer-term follow-up, the evidence showing an OS benefit is less clear, and toxicity is greater with combination therapy compared with sequential single-agent therapy. For example, with longer follow-up of the data for axitinib plus pembrolizumab, the early trend toward survival benefit in the first interim analysis (HR, 0.64; 95% CI, 0.25-1.68)1 did not persist in the analysis conducted with a longer follow-up time, a median of 30.6 months (HR, 1.06; 95% CI, 0.60-1.86).6 Similarly, whether early strong signals of benefit with the cabozantinib/nivolumab and lenvatinib/pembrolizumab regimens in those studies’ overall population persist at longer-term follow-up remains to be seen. Thus far, the reported data specifically in the IMDC favorable-risk subgroup for both cabozantinib/nivolumab (HR, 0.84; 95% CI, 0.35-1.97)3 and lenvatinib/pembrolizumab (HR, 1.15; 95% CI, 0.55-2.40)2 remain immature, with few reported deaths and wide confidence intervals. It remains reasonable to treat select patients with favorable-risk disease with TKI monotherapy and to use immunotherapy as second-line therapy.

Patients who require second-line therapy after an initial immunotherapy-containing regimen may be treated with potent TKIs, such as cabozantinib, or with combinations, such as lenvatinib/everolimus (Afinitor). Thus far, the data do not support routine rechallenge with anti–PD-1 therapy after cancer progression on prior anti–PD-1 therapy. Ongoing clinical trials are exploring whether synergy between a TKI and an anti–PD-1 agent will result in resensitization to immunotherapy. However, this approach remains experimental until we have results from studies such as CONTACT-03 (NCT04338269), which is investigating second-line cabozantinib with or without atezolizumab (Tecentriq) after prior immunotherapy.

One of the most striking aspects of both first- and second-line treatment decision-making is that predictive factors or biomarkers, besides IMDC risk stratification, are absent. This lack of predictive biomarkers highlights a major unmet need in the field. In the future, we hope that a combination of factors—for example, PD-L1 status, histologic classification, or molecular profiling—will help guide treatment. Many studies, including correlative aspects of the interventional trials, are pending with this goal in mind.

In conclusion, the field of kidney cancer is evolving so rapidly that optimal therapy sequencing is a steep challenge. Ultimately, using our most effective therapies up-front will result in the most benefit in the highest numbers of patients. However, it will remain a challenge to appropriately sequence therapies to balance added toxicity of combination treatments with potential benefit.

References

1. Rini BI, Plimack ER, Stus V, et al; KEYNOTE-426 Investigators. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116-1127. doi:10.1056/NEJMoa1816714

2. Motzer R, Alekseev B, Rha S-Y, et al; CLEAR Trial Investigators. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716

3. Choueiri TK, Powles T, Burotto M, et al; CheckMate 9ER Investigators. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384(9):829-841. doi:10.1056/NEJMoa2026982

4. Motzer RJ, Tannir NM, McDermott DF, et al; CheckMate 214 Investigators. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277-1290. doi:10.1056/NEJMoa1712126

5. Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1103-1115. doi:10.1056/NEJMoa1816047

6. Powles T, Plimack ER, Soulières D, et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol. 2020;21(12):1563-1573. doi:10.1016/S1470-2045(20)30436-8

Download Issue PDF
Articles in this issue

Clinical Trials in Progress: COMMIT Study
Clinical Trials in Progress: COMMIT Study
Friendly Competition Fosters Progress in Hematologic Malignancies
Friendly Competition Fosters Progress in Hematologic Malignancies
Improving Outcomes  After Frontline Therapy
Improving Outcomes After Frontline Therapy
The Future of Oncology: Supply and Demand for Oncology Services
The Future of Oncology: Supply and Demand for Oncology Services
Expert Commentary on the Product Profile of  Tazemetostat for Follicular Lymphoma
Expert Commentary on the Product Profile of Tazemetostat for Follicular Lymphoma
Mucinous Adenocarcinoma of the Appendix With Histologic Response to Neoadjuvant Chemotherapy: Review of Histologic and Clinical Spectrum of Epithelial Neoplastic Mucinous Lesions of the Appendix
Mucinous Adenocarcinoma of the Appendix With Histologic Response to Neoadjuvant Chemotherapy: Review of Histologic and Clinical Spectrum of Epithelial Neoplastic Mucinous Lesions of the Appendix
Navigating an Optimal Treatment Course for Advanced Kidney Cancer
Navigating an Optimal Treatment Course for Advanced Kidney Cancer
Emergency Fertility Preservation in a Young Woman With Non-Hodgkin Lymphoma
Emergency Fertility Preservation in a Young Woman With Non-Hodgkin Lymphoma
Routine Breast Cancer Screening in Average-Risk Women Younger Than  50 Years: Current Paradigms  Based on National Guidelines
Routine Breast Cancer Screening in Average-Risk Women Younger Than 50 Years: Current Paradigms Based on National Guidelines
Radiotherapy for Oligometastatic Non–Small Cell Lung Cancer: Past, Present, and Future
Radiotherapy for Oligometastatic Non–Small Cell Lung Cancer: Past, Present, and Future
Second-Line Therapies in the Changing Landscape of First-Line Therapies for Metastatic Clear Cell Renal Cell Cancer
Second-Line Therapies in the Changing Landscape of First-Line Therapies for Metastatic Clear Cell Renal Cell Cancer

Newsletter

Stay up to date on recent advances in the multidisciplinary approach to cancer.

Subscribe Now!
Recent Videos
An ongoing phase 1 trial seeks to prove XmAb819 as an effective treatment and ENPP3 as a plausible target in patients with relapsed or refractory RCC.
“The therapy is designed to prevent both CAR T-cell inactivation and to restore the anti-tumor immunity of the white blood cells that have gotten through the tumor,” said Marasco, MD, PhD.
Ongoing studies aim to combine base immunotherapy regimens with novel agents to potentially improve outcomes among patients with kidney cancer.
Investigators have found a way to reduce liver and biliary toxicity when targeting the molecule CAIX in patients with clear cell renal cell carcinoma.
Neoantigen-targeting vaccines resulted in an absence of recurrence in 9 patients with high-risk kidney cancer, according to David A. Braun, MD, PhD.
The Kidney Cancer Research Consortium may allow collaborators to form more mechanistic and scientifically driven efforts in the field.
Wayne A. Marasco, MD, PhD, stated that by targeting 2 molecules instead of 1, higher levels of tumor cell killing can be achieved in patients with clear cell renal cell carcinoma.
Related Content

Personalized kidney cancer vaccines may help guide immune therapies to more effectively attack cancerous cells while mitigating harm to healthy tissue.

Personalized Cancer Vaccines May Transform Treatment Options in Kidney Cancer

Roman Fabbricatore
July 25th 2025
Article

Personalized kidney cancer vaccines may help guide immune therapies to more effectively attack cancerous cells while mitigating harm to healthy tissue.


Unveiling Advances in GU Cancers: Insights from Oncology Decoded

Unveiling Advances in GU Cancers: Insights from Oncology Decoded

Manojkumar Bupathi, MD, MS;Benjamin Garmezy, MD;John Burke, MD;Dhaval R. Shah, MBBS
July 3rd 2025
Podcast

Dive into the latest in genitourinary oncology with "Oncology Decoded," featuring discussions on KEYNOTE-564 with RCC.


A genitourinary oncologist explained that KIM-1 can be used diagnose, risk-stratify, detect, and monitor disease treatment in patients with kidney cancers.

Analyzing Natural Killer Cell Restoration/KIM-1 Biomarker in Kidney Cancer

Roman Fabbricatore
July 24th 2025
Article

A genitourinary oncologist explained that KIM-1 can be used diagnose, risk-stratify, detect, and monitor disease treatment in patients with kidney cancers.


Beyond Surgery: The Evolving Landscape of Adjuvant Therapy in Kidney Cancer

Beyond Surgery: The Evolving Landscape of Adjuvant Therapy in Kidney Cancer

Manojkumar Bupathi, MD, MS;Benjamin Garmezy, MD
May 1st 2025
Podcast

Oncology Decoded hosts discuss adjuvant therapy in kidney cancer, including research, treatment strategies, and management of recurrence.


CAR T-Cell Therapy to Target CAIX/CD70 Overexpression in ccRCC

CAR T-Cell Therapy to Target CAIX/CD70 Overexpression in ccRCC

Ashley Chan
July 19th 2025
Article

Researchers developed a CAR T-cell therapy to target CAIX/CD70 overexpression for patients with clear cell RCC.


Potential Biomarker May Predict Outcomes/Response in RCC

Potential Biomarker May Predict Outcomes/Response in RCC

Kyle Doherty
July 18th 2025
Article

A new biomarker, KIM-1, has the potential to show outcomes and response for patients with renal cell carcinoma.

Related Content

Personalized kidney cancer vaccines may help guide immune therapies to more effectively attack cancerous cells while mitigating harm to healthy tissue.

Personalized Cancer Vaccines May Transform Treatment Options in Kidney Cancer

Roman Fabbricatore
July 25th 2025
Article

Personalized kidney cancer vaccines may help guide immune therapies to more effectively attack cancerous cells while mitigating harm to healthy tissue.


Unveiling Advances in GU Cancers: Insights from Oncology Decoded

Unveiling Advances in GU Cancers: Insights from Oncology Decoded

Manojkumar Bupathi, MD, MS;Benjamin Garmezy, MD;John Burke, MD;Dhaval R. Shah, MBBS
July 3rd 2025
Podcast

Dive into the latest in genitourinary oncology with "Oncology Decoded," featuring discussions on KEYNOTE-564 with RCC.


A genitourinary oncologist explained that KIM-1 can be used diagnose, risk-stratify, detect, and monitor disease treatment in patients with kidney cancers.

Analyzing Natural Killer Cell Restoration/KIM-1 Biomarker in Kidney Cancer

Roman Fabbricatore
July 24th 2025
Article

A genitourinary oncologist explained that KIM-1 can be used diagnose, risk-stratify, detect, and monitor disease treatment in patients with kidney cancers.


Beyond Surgery: The Evolving Landscape of Adjuvant Therapy in Kidney Cancer

Beyond Surgery: The Evolving Landscape of Adjuvant Therapy in Kidney Cancer

Manojkumar Bupathi, MD, MS;Benjamin Garmezy, MD
May 1st 2025
Podcast

Oncology Decoded hosts discuss adjuvant therapy in kidney cancer, including research, treatment strategies, and management of recurrence.


CAR T-Cell Therapy to Target CAIX/CD70 Overexpression in ccRCC

CAR T-Cell Therapy to Target CAIX/CD70 Overexpression in ccRCC

Ashley Chan
July 19th 2025
Article

Researchers developed a CAR T-cell therapy to target CAIX/CD70 overexpression for patients with clear cell RCC.


Potential Biomarker May Predict Outcomes/Response in RCC

Potential Biomarker May Predict Outcomes/Response in RCC

Kyle Doherty
July 18th 2025
Article

A new biomarker, KIM-1, has the potential to show outcomes and response for patients with renal cell carcinoma.

Advertisement
About
Advertise
CureToday.com
OncLive.com
OncNursingNews.com
TargetedOnc.com
Editorial
Contact
Terms and Conditions
Privacy
Do Not Sell My Personal Information
Contact Info

2 Commerce Drive
Cranbury, NJ 08512

609-716-7777

© 2025 MJH Life Sciences

All rights reserved.