Phase II open-label study of sunitinib in patients with advanced breast cancer

Abstract

This multicenter, open-label phase II study was conducted to evaluate sunitinib monotherapy in patients with either metastatic or locoregionally recurrent advanced breast cancer. Patients received sunitinib 37.5 mg on a continuous daily dosing schedule. The primary endpoint was objective response rate (ORR); the predefined target ORR was 25 %. All 83 patients enrolled into the study received study treatment. The majority of patients (90 %) had metastatic disease; 92 % had received prior systemic therapies, and 60 % had received two or more regimens for early and/or advanced disease. The ORR was 8 % (95 % exact CI, 4-17), comprising seven partial responses. In patients with superficial lesions (defined as cutaneous or palpable chest wall lesions), the ORR was 20 % (three of 15 evaluable patients), which was higher than that in patients with non-superficial disease (9 %; six of 64 patients). Median progression-free survival in the overall population was 3.6 months (95 % CI, 2.4-3.9); median overall survival was 15.6 months (95 % CI, 14.0-22.7). No new or unexpected safety findings were reported. The most commonly reported adverse events (AEs) were fatigue (60 %), diarrhea (54 %), and nausea (49 %). The most commonly reported grade 3/4 AEs were fatigue (17 %), neutropenia (16 %), and thrombocytopenia (11 %). Four patients (5 %) had a dose reduction due to an AE, and 39 patients (47 %) had temporary discontinuations of therapy due to AEs. Two on-study deaths were reported, one due to a pulmonary embolism (considered related to treatment) and one attributed to dyspnea and a myocardial infarction (considered unrelated to treatment). Patient-reported outcomes suggested that sunitinib treatment did not have a negative impact overall on patients' functional domains or the majority of symptom scales. The trial did not meet its prespecified primary endpoint, and in view of the negative results obtained in several other trials, sunitinib will not be developed further for this indication.

Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer

“…The efficacy of VEGFR2 TKI single agent and combination regimens in MBC patients are summarized in Supporting Information Table 4. Only five prior studies (three with sunitinib, two with sorafenib) evaluated the efficacy of VEGFR2 inhibitor single agent in patients with MBC exposed to anthracyclines and/or taxanes . Although direct intertrial comparisons of CBRs may not be appropriate due to large patient heterogeneity, the CBR difference between apatinib and other antiangiogenesis TKIs, such as sunitinib or sorafenib is notable, justifying further confirmation in future trials.…”

Inhibition of RET Increases the Efficacy of Antiestrogen and Is a Novel Treatment Strategy for Luminal Breast Cancer

“…Some response has been demonstrated in these highly selected patients. Most investigators have suggested that combination therapy be considered as mono-therapy failed to demonstrate improved response compared to more conventional agents (33–37). Vandetanib has been examined in small series of breast cancer patients with refractory metastatic disease.…”

Apatinib for metastatic breast cancer in non-clinical trial setting: Satisfying efficacy regardless of previous anti-angiogenic treatment

“…[11][12][13][14] Anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs), such as sunitinib and sorafenib, demonstrate limited clinical benefits and thus they are not used in routine clinical practice. 2,[15][16][17][18] Recently, apatinib, a novel TKI targeting VEGFR-2, has shown satisfying efficacy on various types of cancers with acceptable toxicities. [4][5][6][19][20][21][22][23] Apatinib first made a name of itself for its remarkable survival benefits in patients with metastatic gastric cancer (GC) in a phase III clinical trial, and thus, it has been approved by the China Food and Drug Administration for the third-line treatment of GC.…”