Health Outcomes Research

Health outcomes research represents another area that can inform decision making for clinicians treating renal cell carcinoma, according to Dr. Choueiri.

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“One interesting report relevant for all of us who treat kidney cancer, is that actual practice is not always in sync with level I evidence.”

Applying the International Metastatic RCC Database Consortium criteria leaves 35% of mRCC patients ineligible for participation in clinical trials, he noted.5

Dr. Choueiri also highlighted a study of the impact of angiotensin system inhibitors (ASIs) on outcomes in patients with mRCC, based on Pfizer’s pooled clinical trials database.6

That study found that ASI users with mRCC demonstrated improved overall survival (OS) compared to users of other antihypertensive agents or no antihypertension medications. The OS benefit was associated with ASI users who were undergoing VEGF-targeted therapy but not temsirolimus or interferon-alfa (IFN-α).

Biomarkers

2014 saw numerous reports on candidate biomarkers, Dr. Choueiri noted. “Unfortunately, none are ready for use,” he said.

But insights and advances of note were reported for biomarkers for cytokines and programmed death-1 ligand (PD-L1) with its receptor (PD-1) as a potential biomarker of VEGF-targeted therapy in advanced RCC.7,8

RELATED: Proteomic Markers Might Predict Clear Cell Renal Cell Carcinoma Survival

“PD-L1-positivity predicts worse outcomes to VEGF TKIs but PD-L1 IHC assay urgently needs to be standardized,” he said.

Genomic alterations in mTOR/TSC1 were also reported to be associated with “exceptional responses” to rapalog (rapamycin and rapamycin-analog) mTOR-inhibitors, Dr. Choueiri noted.9

Symposium keynote speaker Daniel J. George, MD, of the Duke Cancer Center in Durham, NC, subsequently identified what he said were the most important unmet needs in metastatic RCC:

1. Identification of the mechanisms that allow mRCC cell immune-escape.
2. Development and validation of tumor predictors of responses to treatment.
3. Establishment of an international registry of metastatic RCC patients with tissue, imaging and outcomes data.
4. Development of genetically-engineered mouse models that better approximate human clear cell RCC.
5. Molecular genetic characterization of non-clear cell RCC and testing of targeted therapies against this malignancy.
6. Identification of therapeutic targets downstream of Ch 3p21 tumor suppressor mutations.


References

  1. Motzer RJ, Jonasch E, Agarwal N, et al. Kidney cancer, version 3.2015. J Natl Compr Canc Netw. 2015;13:151-159.
  2. Motzer RJ, Hutson TE, McCann L, et al. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib.N Engl J Med 2014;370(18):1769-1770.
  3. Hutson TE, Escudier B, Esteban E, et al. Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014;32(8):760-767.
  4. Motzer RJ, Barrios CH, Kim TM, et al. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014;32(25):2765-2772.
  5. Heng DY, Choueiri TK, Rini B, et al. Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials. Ann Oncol. 2014;25(1):149-154. 
  6. McKay RR, Rodriguez GE, Lin X, et al. Angiotensin system inhibitors and survival outcomes in patients with metastatic renal cell carcinoma. Clin Cancer Res. February 27, 2015. [Epub ahead of print] pii: clincanres.2332.2014.
  7. McDermott DF, Cheng SC, Signoretti S, et al. The high-dose aldesleukin “select” trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2015;21(3):561-568.
  8. Choueiri TK, Figueroa DJ, Fay AP, et al. Correlation of PD-L1 Tumor Expression and Treatment Outcomes in Patients with Renal Cell Carcinoma Receiving Sunitinib or Pazopanib: Results from COMPARZ, a Randomized Controlled Trial. Clin Cancer Res. December 23, 2014. [Epub ahead of print] http://clincancerres.aacrjournals.org/content/early/2015/02/03/1078-0432.CCR-14-1993.long
  9. Voss MH, Hakimi AA, Pham CG, et al. Tumor genetic analyses of patients with metastatic renal cell carcinoma and extended benefit from mTOR inihibitor therapy. Clin Cancer Res. 2014;20(7):1955-1964.

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GU Symposium 2015 Kidney Cancer Renal Cell Carcinoma