<--GAT-->
Clinical Topics

Targeted Therapies Transform RCC Treatment Over Last Decade

by U.S. Medicine

June 19, 2018

WASHINGTON — In the last decade, the development of multiple molecular-targeted therapies has dramatically altered the treatment landscape for advanced renal cell carcinoma (RCC).

The rate of new drug approvals has outpaced the ability of most guidelines to keep up, with four therapies receiving approval or breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) in just the last year.

The following are approved targeted therapies for metastatic RCC with approval dates:

  • Sorafenib (2005)
  • Sunitinib (2006 for first-line use and in 2017 for adjuvant therapy)
  • Temsirolimus (2007)
  • Pazopanib (2009)
  • Everolimus (2009)
  • Bevacizumab + interferon alfa-2b (2010)
  • Axintinib (2012)
  • Nivolumab (2015)
  • Lenvatinib + everolimus (2016)
  • Cabozantinib (2017)
  • Nivolumab+ ipilimumab (2018), for patients with intermediate or poor risk

In addition, pembrolizumab plus lenvatinib and axitinib plus avelumab have received breakthrough therapy designation in the last year.

The targeted therapies fall into two main classes, vascular endothelial growth factor (VEGF) inhibitors or mammalian target of rapamycin (mTOR) inhibitors. The National Comprehensive Cancer Network (NCCN) recommends the VEGF inhibitors sunitinib, pazopanib, bevacizumab plus interferon alpha, and cabozantinib in the first-line setting for primarily clear cell renal cell carcinoma. Sorafenib, axitinib and lenvatinib plus everolimus are NCCN recommended second-line therapies.

Of the mTOR inhibitors, NCCN recommends temsirolimus as a first-line therapy for poor-prognosis patients. Everolimus is recommended as a second-line option.

The newest approved agent, nivolumab plus ipilimumab, combines two immune checkpoint inhibitors. Nivolumab targets the programmed death 1 (PD-1) checkpoint protein, while the monoclonal antibody ipilimumab inhibits the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) protein. The combination received FDA approval subsequent to publication of the 2018 NCCN guidelines.

In the phase 3 CheckMate-214 trial on which the FDA based its decision, the nivolumab/ipilimumab combination demonstrated a survival benefit as well as both higher response rates and more durable responses compared to sunitinib in patients with intermediate to poor risk. With a median follow-up of 25.2 months, patients on the combination drug had an 18-month overall survival of 75% and median overall survival was not reached, while those receiving sunitinib had a 60% 18-month overall survival and a median overall survival of 26 months. The combination reduced the risk of progression or death by 28% compared to the standard therapy.1


1Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, et. Al. CheckMate 214 Investigators. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi:10.1056/NEJMoa1712126. Epub 2018 Mar 21. PubMed PMID: 29562145.

Related Articles

VA/National Cancer Institute Partnership Increases Veteran Access to Trials

Thanks to a new partnership between the National Cancer Institute and the VA, veterans with cancer will now have greater access to potentially lifesaving clinical trials.

VA Continues Hepatocellular Screening, but Study Questions the Value

Although a recent study determined that screening veterans with cirrhosis for hepatocellular carcinoma did not reduce the risk of death associated with liver cancer, the VA has no plans to change its screening practices.


U.S. Medicine Recommends


More From oncology

Oncology

VA/National Cancer Institute Partnership Increases Veteran Access to Trials

Thanks to a new partnership between the National Cancer Institute and the VA, veterans with cancer will now have greater access to potentially lifesaving clinical trials.

Oncology

VA Continues Hepatocellular Screening, but Study Questions the Value

Although a recent study determined that screening veterans with cirrhosis for hepatocellular carcinoma did not reduce the risk of death associated with liver cancer, the VA has no plans to change its screening practices.

Oncology

Testosterone Therapy Not Linked to Aggressive Prostate Cancer in Veterans

Clinicians prescribing supplemental testosterone in men with low levels always have a nagging concern about the possible link between increasing hormone levels and prostate cancer.

Oncology

Side-effects Differ Between Radiation Therapies for Prostate Cancer

A recent study compared patient-reported disease-specific functional outcomes after external beam radiation therapy (EBRT) and EBRT combined with low-dose-rate brachytherapy prostate boost (EB-LDR) among men with localized prostate cancer.

Oncology

Parkinson's Drug Not Associated With Higher Prostate Cancer Risk

An increased incidence of prostate cancer was observed in Parkinson's disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial, according to a new study which noted that the relationship had not yet been intensely investigated.

Facebook Comment

Subscribe to U.S. Medicine Print Magazine

U.S. Medicine is mailed free each month to physicians, pharmacists, nurse practitioners, physician assistants and administrators working for Veterans Affairs, Department of Defense and U.S. Public Health Service.

Subscribe Now

Receive Our Email Newsletter

Stay informed about federal medical news, clinical updates and reports on government topics for the federal healthcare professional.

Sign Up