Prospective phase II study of sunitinib rechallenge in metastatic renal cell carcinoma: The “retry” study from the Italian Group of Onco-Nephrology (G.I.O.N.)

Background: Sunitinib is still a recommended treatment option for metastatic renal cell carcinoma (RCC) patients; lack of cross-resistance to sequential antiangiogenic drugs has been postulated. Objective: The possibility of a successful rechallenge with sunitinib was tested in this prospective phase II trial. Methods: Main inclusion criteria were: histologically proven RCC with clear cell component, previous first-line sunitinib with a Disease Control Rate lasting ⩾10 months, and second-line everolimus. The primary end-point was 6-months progression-free survival (PFS). A Simon’s 2-stage design was used; after testing sunitinib on 12 patients, the trial would have been terminated if ⩽5 had a PFS <6 months. Otherwise, the trial would have proceeded enrolling a total of 38 patients. If the total number of patients free of progression at 6 months would have been ⩽18, sunitinib would have been rejected. Results: A total of 39 patients (30 males, 9 females) were enrolled. The study reached the second stage, and ultimately succeeded; indeed, 6-months PFS was 64.1%, median PFS being 14.9 months (95% confidence interval: 9.06–20.91). Treatment-related grade 3–4 adverse events observed in ⩾5% of the patients were: hand-foot skin reaction, fatigue, nausea, hypertriglyceridemia, hypophosphatemia, hypocalcemia, hyperglycemia, and neutropenia. One case each of myocardial infarction, atrial flutter, and spontaneous pneumothorax, were also reported. Conclusions: Despite an ineluctable time-lead-bias, median PFS on sunitinib rechallenge was high, clearly showing that many patients may become sensitive again to antiangiogenic treatment. In countries where treatment options are still limited, sunitinib rechallenge could represent an option. EudraCT number: 2012-000473-23.