A prospective phase II trial of gemcitabine plus axitinib in patients with sarcomatoid type renal carcinoma.
616 Background: Sarcomatoid renal cell carcinoma (SRCC) is a rare but very aggressive type of RCC. The treatment option for SRCC is very limited, and there have been anecdotal reports of very good responders to gemcitabine or vascular endothelial growth factor receptor tyrosine kinaase inhibitors (VEGFR TKI). We conducted multicenter phase 2 trial of gemcitabine plus axitinib (GX) in patients (pts) with recurrent or metastatic SRCC to evaluate its efficacy and safety. Methods: Eligibility criteria included histologically confirmed metastatic or recurrent RCC with sarcomatoid component of 25% or more on resected kidney or exclusive sarcomatoid carcinoma on needle biopsy, ECOG PS 0-2, measurable lesion by RECIST v1.1, and adequate cardiac, hepatic, renal and bone marrow function. Pts with uncontrolled hypertension, prior exposure to gemcitabine or VEGFR TKI were exclude. Pts received gemcitabine 1,000 mg/m2 intravenously on days 1 and 8 by 3-week cycle and axitinib 5 mg twice daily. The primary endpoint was objective response rate (ORR) according to RECIST v1.1, and secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity. Results: Twenty-five pts were enrolled between Oct 2014 and Aug 2018. Median age was 61 (range 33-80), and 84% was male. ECOG PS were 1 (92%) and 2 (8%), and 52% had prior nephrectomy. Clear cell carcinoma was the most common histology of carcinoma component, and median percentage of sarcomatoid component was 90% (25-100%). Pts belonged to intermediate (28%) and poor (72%) risk group according to IMDC risk stratification. Median 6 cycles of GX were administered, and 56%, 28%, and 12% of pts achieved PR, SD, and PD, respectively, with an ORR of 56% and median duration of response of 2.5 months. With a median follow-up duration of 21.4 mo, median PFS was 4.9 mo (95% CI, 3.5-13.3), and median OS was 8.4 months (95% CI 3.5-13.3 months). Most adverse events were manageable, and no unexpected toxicities were found. One pt died of grade 5 pneumonia. Conclusions: GX showed promising efficacy in pts with SRCC. GX might be considered as one of treatment options for pts with SRCC, although efficacy of GX should be confirmed in larger trial.