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

• Published in: Clinical genitourinary cancer Vol. 21; no. 5; pp. 546 - 554
• Main Authors: Carthon, Bradley C., Kim, Se Eun, McDermott, David F., Dutcher, Janice P., Puligandla, Maneka, Manola, Judith, Pins, Michael, Carducci, Michael A., Plimack, Elizabeth R., Appleman, Leonard J., MacVicar, Gary R., Kohli, Manish, Kuzel, Timothy M., DiPaola, Robert S., Haas, Naomi B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2023
• Subjects: Antineoplastic Agents - therapeutic use; Carcinoma, Renal Cell - pathology; Gemcitabine; Humans; Kidney Neoplasms - pathology; Renal Cell; Sarcomatoid; Sunitinib; Sunitinib - therapeutic use; Sarcomatoid; Sunitinib; Gemcitabine; Renal Cell
• ISSN: 1558-7673; 1938-0682; 1938-0682
• DOI: 10.1016/j.clgc.2023.06.012

•Sarcomatoid RCC is an aggressive and rapidly growing histological variant with poor outcomes.•Prior data has shown limited effective options exist for this variant.•This demonstrates that cytotoxic chemotherapy in addition to VEGF inhibitors has limited effect and efficacy in these patients.•Novel therapeutic options will need to be examined in this subset of renal cell carcinoma patients. 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 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. Patients with sarcomatoid renal cancer in good, intermediate and poor prognostic groups were randomized 1:1 sunitinib and gemcitabine (SG) versus sunitinib and assessed for response rate in this cooperative group phase II trial. Sunitinib but not the SG met the preset threshold of success. Grade ≥ 3 events were seen. EA1808 was the first randomized cytotoxic trial for sarcomatoid RCC.