Results From a Randomized Phase II Trial of Sunitinib and Gemcitabine or Sunitinib in Advanced Renal Cell Carcinoma with Sarcomatoid Features: ECOG-ACRIN E1808.

Sarcomatoid renal cancer (sRCC) patients have poor outcomes. EA1808 evaluated sunitinib and gemcitabine (SG) and sunitinib alone (S) in sRCC in a randomized cooperative group phase II trial (NCT01164228).

Pts were aggregated 1:1 to SG (45 pts) or S (40 pts) using a 2-stage design. sRCC pts with ≤ 1 prior nonvascular endothelial growth factor tyrosine kinase inhibitor were stratified into prognostic groups: good (clear cell, < 20% sarcomatoid, PS 0), intermediate (20%-50% sarcomatoid, PS 0), and poor (nonclear cell or > 50% sarcomatoid or PS 1). The primary endpoint was response rate (RR). For SG, the null RR was 15% and a 30% RR was of interest. For S, a 20% RR was of interest vs. a 5% null rate. Secondary endpoints were progression-free survival, overall survival, and safety.

Both arms met protocol criteria for stage 2 of accrual. A total of 47 pts were randomized to SG and 40 to S. The SG arm had 9 of 45 evaluable patient responses (RR of 20%; CI = [13%-31%]) not meeting the predetermined threshold for success. The sunitinib arm met its endpoint with 6/37 (RR of 16%; CI = [9%-27%]) evaluable responses. Grade ≥ 3 events were experienced by 36 in the SG arm and 17 in the sunitinib arm CONCLUSIONS: EA1808 was the largest and first randomized cytotoxic trial for sarcomatoid RCC. Sunitinib alone but not the SG met the preset threshold of success. Cytotoxic chemotherapy is only useful in limited clinical scenarios for sRCC.

Clinical genitourinary cancer. 2023 Jul 03 [Epub ahead of print]

Bradley C Carthon, Se Eun Kim, David F McDermott, Janice P Dutcher, Maneka Puligandla, Judith Manola, Michael Pins, Michael A Carducci, Elizabeth R Plimack, Leonard J Appleman, Gary R MacVicar, Manish Kohli, Timothy M Kuzel, Robert S DiPaola, Naomi B Haas

Department of Medicine, Winship Cancer Institute, Emory University, Atlanta, GA., Department of Statistics, Dana-Farber Cancer Institute, Boston, MA., Division of Hematology/Oncology; Beth Israel Deaconess Medical Center, Boston, MA., Cancer Research Foundation of New York, Chappaqua, NY., Department of Pathology; Advocate Lutheran General Hospital, Park Ridge, IL., Division of Hematology /Oncology; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD., Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA., Department of Medicine; University of Pittsburgh Medical Center, Pittsburgh, PA., Department of Medicine; Illinois Cancer Care, Peoria, IL., Department of Medicine; University of Utah, Salt Lake City, UT; Department of Medicine; Mayo Clinic, Rochester, MN., Department of Medicine; Northwestern University, Chicago, IL., Department of Medicine; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ., Department of Medicine; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA. Electronic address: .