Our 80-year-old patient achieved stable disease after a partial remission for long duration under sunitinib for metastatic renal cell carcinoma. After sunitinib discontinuation, progression-free survival was 13 months. Our observation contributes important data to the ongoing discussion on the discontinuation of treatment with kinase inhibitors. This case demonstrates that patients with mRCC can be taken off antiangiogenic-targeted therapy and suggests that continuous sunitinib may not be necessary in all patients. Although targeted therapies are currently a standard frontline therapy for metastatic renal cell carcinoma patients with a good or intermediate prognosis according to several phases III studies [
1‐
12]. These therapeutic agents have substantially improved patient outcomes. Objective responses, mostly partial responses, are observed in approximately 8% to 39% of patients with median OS of more than 2 years observed with sunitinib [
1,
2]. These targeted agents should be continued in cancer therapy until disease progression or toxicity, especially in the targeted therapy era [
1,
13,
14]. However, in view of the fact that target agents of mRCC in general remains a palliative in the majority of cases, accompanied by chronic adverse events such as fatigue, diarrhea, hand-foot syndromes, proteinuria, and renal insufficiency, impairment of quality of life, and also the high cost of continuous long-term therapy of these therapies are becoming increasingly important issues. A key question surrounding long disease control for long periods is whether or not treatment can be discontinued without negatively impacting outcomes and whether this will reduce treatment-related side effects and improve quality of life. In routine clinical practice, 20–30% of patients experienced grade 3/4 toxicities, and treatment modifications occurred in 50–55% patients because of adverse events. Finally, up to 20% patients discontinued TKI therapy because of adverse events [
1,
2,
13]. Our case illustrates achievement of partial response with sunitinib and prolonged sustained response even after sunitinib discontinuation. Several retrospective studies have suggested that discontinuation of TKI therapy is possible in carefully selected patients and may improve symptoms of toxicity [
15,
16]. In contrary, preclinical models have mentioned rebound effect, with rapid regrowth and development of metastases observed after treatment discontinuation with TKIs [
17]. In addition, continuation of angiogenesis inhibition in mRCC is supported by clinical evidence that switching to another vascular endothelial growth factor (VEGF) inhibitor in mRCC may increase OS in patients previously treated with sunitinib. However, this strategy had been tested in clinical practice with ambiguous results [
18,
19]. In clinical practice Iacovelli and colleagues analyzed the follow-up of 63 patients with mRCC after discontinuation of anti-vascular endothelial growth factor receptor (VEGFR) TKI. They found that tumor regrowth after discontinuation of therapy was related to the reason for discontinuation; regrowth was higher in patients who discontinued treatment because of disease progression, and lower in patients who discontinued treatment because of a sustained response [
20]. Koo and colleagues report that VEGFR-TKI could be interrupted, at least temporarily, when clinically warranted in patients with mRCC sufficiently controlled by TKI and duration of TKI therapy (< 1 year) before TKI discontinuation was an independent significant prognostic factor of poor PFS (
p = 0.045) [
21]. To date none of the cancer guidelines recommends sunitinib discontinuation for mRCC. Regarding our patient, it is remarkable that RCC relapsed after a disease-free period of more than 10 years, he presents an indolent disease managed by active surveillance before deliberately deferred sunitinib. He achieved a partial response with long-term disease stabilization response to sunitinib for 28 months. During a follow-up of 13 months, no signs of significant tumor growth could be found neither clinically nor in MRI performed; for this the discontinuation will be prolonged. Our observation and several smaller studies have suggested that discontinuation of antiangiogenic therapy is possible in carefully selected patients and may improve symptoms of toxicity without loss of response to the same targeted agent, which was usually restarted after relapse [
22‐
24]. The selection of patient candidates for sunitinib discontinuation should be rational, taking into account favorable Heng prognostic risk criteria, long disease-free interval from the time of nephrectomy to the diagnosis of metastasis, indicates a biological pattern of slow growth, disease typically limited to one or two sites with good Eastern Cooperative Oncology Group Performance Status (ECOG PS), and have disease control for a long period under sunitinib for the benefit to be optimal as in our case. A strategy of periodic treatment breaks, therefore, may allow for a reduction in overall toxicity and increase in patient quality of life while maintaining overall disease control with these noncurative therapies.