Use of biomakers to predict outcomes of immunotherapy for metastatic renal cell carcinoma

Abstract

16015 Background: Metastatic renal cell carcinoma (RCC) is known to have poor and unpredictable course. Moreover, there are no reliable prognostic or predictive molecular markers. The aim of this study is to determine the novel biologic marker which is associated with response to immunotherapy. Methods: Between 1995 and 2006 at Samsung Medical Center, tissue specimens were obtained from 57 patients with metastatic RCC had received combination of high dose interleukin-2 and interferon-α based therapy. Paraffin- embedded RCC tumor samples were immunostained for carbonic anhydrase IX (CAIX) and cyclooxygenase-2 (COX-2) expression to determine predictive or prognostic potential. Results: With median 50 months of follow-up, 57 patients had received median 16 (4–24) weeks of immunotherapy. Forty seven specimens (82.4%) were assessed as clear cell and three (5.3%), four (7.0%), and three (5.3%) patients were classified as sarcomatoid, papillary, and undifferentiated carcinoma. Fourteen out of 17 responding patients (6 complete responses and 11 partial response) exhibited high CAIX (> 85% of tumor cells stained) compared with only 19 of 40 nonresponding patients exhibited low CAIX staining (relative risk, 5.2, 95% CI=1.3–20.8, P=0.02). CAIX immunostaining was an independent prognostic factors for progression free survival in favor of high CAIX immunostaining (adjusted HR=0.31, 95% CI=0.17–0.57, P<0.001). High COX-2 (≥ 50% overall tumor cells stained) contained 10 of 17 (58.8%) responders compared with 7 of 40 (17.5%) nonresponders (relative risk 6.7, 95% CI=1.9–23.8, P=0.004). High COX-2 staining was also an independent prognostic factors for overall survival (adjusted HR=0.23, 95% CI=0.08–0.69). Conclusions: Expression of COX-2 and CAIX seem to be important predictors of outcome in metastatic renal cell carcinoma patients receiving immunotherapy. No significant financial relationships to disclose.