mRCC treatments differ greatly in developed countries vs developing countries

By Liz Meszaros, MDLinx
Published December 8, 2017

Key Takeaways

Treatment patterns for metastatic renal cell carcinoma (mRCC) may be significantly varied between developing and developed countries, according to study results presented here at the Sixteenth International Kidney Cancer Symposium, in Miami, FL. Specifically, researchers found a decreased use of systemic therapy in the second- and third-line settings in Latin America, as well as treatment heterogeneity with many antiquated regimens.

“In the United States, renal cell carcinoma ranks among the 10 most common malignancies, representing 3.8% of all new cancer cases. In Brazil, estimates vary, but the disease still takes a substantial toll, with over 6,000 cases and 3,000 deaths noted per year,” said lead author Paulo Gustavo Bergerot, MD, clinical oncologist, Brazil, and postdoctoral fellow, City of Hope National Medical Center, Duarte, CA, and mentored by Sumanta Kumar Pal, MD.

“There was a very interesting study published last year in the International Journal of Urology by Dr. Pal, using population-based registries in the United States that show a relatively even distribution of use of VEGF TKIs and mTOR inhibitors in the second- and third-line setting. So, in this current study, we sought to determine if similar treatments occurred in Brazil and in the United States,” he added.

Renal cell carcinoma accounts for over 3,000 deaths per year in Brazil. Although previous studies have reported patterns of care for mRCC patients in the US, based on a large retrospective review, Dr. Bergerot and colleagues conducted this study to test their hypothesis that treatment patterns in developing and developed countries will differ significantly from those in the US.

They used the Close-Up International database, which is a commercial dataset with clinical information from private and public institutions in 55 cities across 18 states in Brazil, with 50% in the Southwest region.

They collected data from March 2013 to October 2016 from private and public hospitals in Brazil of patients with mRCC receiving systemic therapy. They extracted basic clinical and demographic data, information to determine Heng risk, and trends in the use of first-, second-, and third-line treatments.

Dr. Bergerot and colleagues included 4,379 patients (median age: 59.5 years; 68% male), of whom 80% had clear cell, 5% non-clear cell, and 14% unknown etiology.  Most patients (48%) were at intermediate Heng risk, with 26% at good risk and 26% at poor risk. A full 91% had metastatic disease.

In all, 79% of patients had undergone first-line treatment, 20% second-line, 5% third-line, and 1% fourth-line treatment. Among these patients, most (86%) received tyrosine kinase inhibitors (TKI) therapy consisting of either sunitinib (56.5%), pazopanib (27.5%), or sorafenib (2.3%). Six percent of patients received first-line treatment with mechanistic target of rapamycin (mTOR) inhibitors, including everolimus (1%) and temsirolimus (5%).

TKI treatment was given to 44.5% of patients as second-line treatment, including sorafenib (15.8%), pazapanib (16.2%), sunitinib (12%), and axitinib (0.5%). In addition, 46.5% of patients were treated with an mTOR inhibitor (everolimus: 39%, temsirolimus: 7.5%), and 9% with another agent.

Finally, as third-line treatment, 33.5% of patients received a TKI (18% sunitinib, 16.5% sorafenib, 13% pazopanib), 47.3% were treated with an mTOR inhibitor (everolimus: 26%, temsirolimus: 8%), and 12.5% with another agent.

When Dr. Bergerot and colleagues compared the use of first-, second-, and third-line therapy in Brazil versus the International mRCC Database Consortium (IMDC) dataset, they also found the following:

  • In both Brazil and IMDC, 100% of patients received first-line therapy.
  • Second-line therapy was given to 20% of patients in Brazil, compared with about 50% of those from the IMDC (P < 0.001).
  • Third-line therapy was given to less than 10% of patients in Brazil, compared with a little over 20% from the IMDC (P < 0.001).

Dr. Bergerot and colleagues concluded, in comparing patient management strategies in Brazil with those in other developed countries, there are differences in the kinds of treatment given to mRCC patients. In addition, they found that vascular endothelial growth factor receptor TKIs are the mainstay of treatment in the first-line setting, with second-line treatment evenly divided between TKI and mTOR inhibitors.

“We could find a substantially heterogeneity in the nature of treatment that is rendered to patients with mRCC in Brazil, with patients receiving many unconventional therapies. Some notable examples of these included imatinib or erlotinib, as well as older cytotoxic drugs such as dacarbazine and doxorubicin. There is very little clinical rationale for rendering these with the availability of current targeted agents,” said Dr. Bergerot.

“Our findings suggest rather concerning rates of attrition between first- and second-line therapy, and also between second- and third-line therapy in this Brazilian cohort versus previously published experiences from IMDC,” he added.

Dr. Bergerot and colleagues also found some very different patterns of care.

"In particular, there is a relatively high incidence of the use of antiquated or unconventional regimens such as targeted therapies approved for lung cancer and other diagnoses, and also cytotoxic chemotherapy that is not typically used in this context anymore. These may reflect a lack of access to targeted therapy or potentially address poor gaps in physician education,” said Dr. Bergerot.

“There are some good initiatives ongoing for a better understanding of this scenario. One of the most important initiatives in Latin America is the Latin America Renal Cancer Group, or LARCG. This is a huge effort that is connecting and accurately integrating the demographic, clinical, and pathological data through several institutions in Latin America, including Brazil,” he concluded.

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