Prospective phase II study of sunitinib rechallenge in metastatic renal cell carcinoma (mRCC): A G.I.O.N. trial

Autor: Andrea Falconeri, Giovanni L. Pappagallo, Paolo Andrea Zucali, Vittorio Ferrari, Alessandra Ferrari, Antonio Bernardo, Giuseppe Fornarini, Camillo Porta, Sandra Santarossa, Alessandra Bearz
Rok vydání: 2017
Předmět:
Zdroj: Journal of Clinical Oncology. 35:e16081-e16081
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2017.35.15_suppl.e16081
Popis: e16081 Background: Sunitinib is a 1st-line standard of care in mRCC. Lack of cross-resistance to sequential VEGF-targeting drugs and the possibility of a successful rechallenge with Sunitinib have been postulated. Whether mRCC patients (pts) could benefit from rechallenge with Sunitinib after progressing on 1st-line Sunitinib and 2nd-line Everolimus was the aim of this phase II study Methods: 39 mRCCpts were prospectively treated with Sunitinib (50 mg/daily, 4:2); main inclusion criteria were: histologically proven RCC with clear cell component, previous 1st-line Sunitinib with a Disease Control Rate lasting at least 10 months, 2nd-line Everolimus, and written informed consent. The primary end-point of this study was 6-months progression-free survival (PFS). A Simon’s 2-stage design was used; after testing Sunitinib on 12 pts in the first stage, the trial would have been terminated if 5 or fewer had a PFS of less than 6 months. Otherwise, the trial would have proceeded to the second stage, enrolling a total of 38 pts. If the total number of pts free of progression at 6 months would have been less than or equal to 18, Sunitinib would have been rejected Results: As a whole, 39 pts (30 males, 9 females) were enrolled. The study quickly moved from the first stage to its completion and ultimately succeeded; indeed, 6-months PFS was 60%, median PFS being 8.6 months (average: 9.59, range: 0.7-24.6 months). In terms of safety no unexpected toxicities were observed. Tx-related grade 3-4 AEs observed in ≥5% of the pts 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, but resolved Conclusions: Despite an ineluctable time-lead-bias, median PFS on Sunitinib rechallenge was high (8.6 months), clearly showing that many pts may become sensitive again to VEGFRs-inhibition. Although many agents are presently available from 2nd-line on, in countries where treatment options are still limited, Sunitinib rechallenge could still represent a reasonable treatment option. EudraCT number: 2012-000473-23. Clinical trial information: 2012-000473-23.
Databáze: OpenAIRE
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