Yael Waknine

June 14, 2012

June 14, 2012 (Chicago, Illinois) — A slew of drug approvals has led to a paradigm shift in the treatment of metastatic renal cell carcinoma. There is now much less surgery carried out, researchers reported in a poster presentation here at the 2012 Annual Meeting of the American Society of Clinical Oncology.

A wave of new drugs has been approved in recent years for the treatment of kidney cancer. Many are vascular endothelial grown-factor receptor tyrosine kinase inhibitors (VEGFR-TKIs), including sorafenib (Nexavar) launched in 2005, sunitinib (Sutent) in 2006, pazopanib (Votrient) in 2009, and axitinib (Inlyta) in 2012. In addition, the VEGF antibody bevacizumab (Avastin) was approved in 2009, and 2 target of rapamycin mTOR inhibitors were approved — temsirolimus (Torisel) in 2007 and everolimus (Afinitor) in 2009.

Before these drugs were approved, a common treatment for kidney cancer was cytoreductive nephrectomy (CyNx). This became a popular surgical option after the publication of data in 2001 from 2 prospective randomized trials — one by the Southwest Oncology Group (SWOG) and the other by the European Organisation for Research and Treatment of Cancer (EORTC).

CyNx use increased from 41% of kidney cancer patients in 2000 to 49% in 2005, the researchers reported at the meeting.

In 2005, the first of the new drugs (sorafenib) was approved. By 2008, only 35% of patients were treated with CyNx, which was a 24% decrease.

"This trend is not surprising, given the uncertainty about the utility of CyNx in the age of VEGFR-TKIs and concerns about delaying effective systemic therapy," lead author Che-kai Tsao, MD, told Medscape Medical News. Dr. Tsao is chief fellow in the division of hematology and medical oncology at the Mount Sinai School of Medicine in New York City.

The study also showed potential socioeconomic and demographic differences in the use of CyNx; nonwhite patients and the elderly were significantly less likely to go under the knife.

According to Nicholas J. Vogelzang, MD, from the Comprehensive Cancer Centers of Nevada in Las Vegas, the findings are spot on.

"The findings confirm my clinical experience," Dr. Vogelzang told Medscape Medical News, noting that the differences in CyNx use are similar to other disparities in cancer therapy.

"I still recommend CyNx to all patients who would benefit and who are candidates for it," Dr. Vogelzang said. He added that he has "long been concerned that CyNx is overused by urologists who do not believe there is effective systemic therapy."

"I have heard too many stories of patients who 'needed a CyNx' and who died or deteriorated before they could get effective systemic therapy," he explained. "The rate of CyNx was too high; it is now more likely at the appropriate level of use."

"The survival improvement in kidney cancer did not come about because of CyNx. It came about when sorafenib, sunitinib, pazopanib, bevacizumab, etc., were FDA approved," Dr. Vogelzang noted. "I have several patients with widespread metastatic renal cell carcinoma who have not needed a CyNX" after for 4 to 5 years of systemic therapy, he added, referring to a study published by he and his colleagues (J Clin Oncol. 2009;27[26]:e106-e107).

Dr. Tsao and colleagues examined data from the Surveillance, Epidemiology and End Results (SEER) registry for 2780 patients with histologically confirmed metastatic renal cell carcinoma who were treated with CyNx or with no surgery from 2001 to 2008.

Differences in baseline characteristics between the 2 groups were assessed and controlled for in a logistic regression analysis to determine the likelihood of undergoing CyNx in the pre-VEGFR-TKI era (2001 to 2005) and in the VEGFR-TKI era (2006 to 2008).

The prevalence of CyNx use was relatively constant from 2001 to 2003 (prevalence ratio [PR], 0.94; 95% confidence interval [CI], 0.82 to 1.09; P = .4120) and from 2003 to 2005 (PR, 1.06; 95% CI, 0.98 to 1.16; P = .1640).

From 2005 to 2008, after the introduction of VEGFR-TKIs, the prevalence of CyNx use significantly decreased by 24% (PR, 0.65; 95% CI, 0.65 to 0.90; P = .0011).

Overall, patients in the VEGFR-TKI era were 9% less likely to undergo CyNx than those in the pre-VEGFR-TKI era (PR, 0.91; 95% CI, 0.84 to 0.99; P = .032).

The researchers reported specific characteristics that affected the use of CyNx. With every 10-year increase in age, patients were 16% less likely to undergo CyNx (PR, 0.84; 95% CI, 0.81 to 0.87; P < .001). Black patients were 18% less likely than white patients to undergo CyNx (PR, 0.82; 95% CI, 0.69 to 0.97; P = .022). Hispanic patients were 14% less likely than white patients to undergo CyNx (PR, 0.86; 95% CI, 0.76 to 0.97; P = .016). Married patients were 25% more likely than unmarried patients to undergo CyNx (PR, 1.25; 95% CI, 1.15 to 1.37; P < .001). Patients with tumors larger than 20 mm were 2% more likely than patients with smaller tumors to undergo CyNx (PR, 1.02; 95% CI, 1.01 to 1.03; P < .001).

Whereas age-related decreases in the use of CyNx can be explained by concerns about increased operative morbidity and mortality in the setting of incurable malignancy, the decreased use in black and Hispanic patients might have more serious implications with respect to treatment access.

"While the underlying biology of the disease may play a role, decreased accessibility and/or acceptability of CyNx is likely a more plausible explanation," explained Dr. Tsao. Other studies have demonstrated these effects with a variety of therapeutic modalities in racial/ethnic minority populations with other solid tumors, he said.

In contrast, patients with social support were more likely to undergo CyNx, as demonstrated by a higher proportion of married than single patients choosing the procedure. "Marital status has been regarded as an important surrogate for social support," Dr. Tsao stated.

Study limitations include a lack of data on the specific systemic therapy administered, patient comorbidities, and clinical outcome.

The role of CyNx in the VEGFR-TKI era remains unclear.

"To our knowledge, our study is the first to evaluate changes in the patterns of use of this modality...and supports the suspected general uncertainty regarding the appropriate integration of surgery in the age of targeted therapeutics," Dr. Tsao said.

"While we identified potential racial, ethnic, and socioeconomic differences in the application of CyNx, the lack of a definitive role for CyNx in the current era limits the extent to which these differences can be considered inappropriate," Dr. Tsao explained. "Results of ongoing randomized trials evaluating the role of CyNx in the VEGFR-TKI era [will help] to optimize use of this treatment modality and to address barriers to accessibility and acceptability if CyNx is proven to be beneficial," he said.

2012 Annual Meeting of the American Society of Clinical Oncology: Abstract 4623. Presented June 3, 2012.

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