Sutent

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Before taking Sutent tell your healthcare provider if you:

• have any heart problems 
• have high blood pressure 
• have thyroid problems 
• plan to have surgery 
• have kidney function problems (other than cancer) 
• have liver problems 
• have any bleeding problem 
• have seizures 
• have any other medical conditions 
• if you are having surgery (including dental surgery)
• are pregnant, could be pregnant or plan to become pregnant. Sutent may harm an unborn baby. You should not become pregnant while taking Sutent. Tell your healthcare provider right away if you become pregnant while taking Sutent. 
• are breastfeeding or plan to breastfeed. You and your healthcare provider should decide if you will take Sutent or breastfeed. You should not do both.


Tell your healthcare provider about all the medicines you take, including prescription medicines and non-prescription medicines, vitamins, and herbal supplements. Using Sutent with certain other medicines can cause serious side effects. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. Talk with your healthcare provider before starting any new medicines.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

• If you have an allergy to sunitinib or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are taking St. John's wort. Do not take St. John's wort with Sutent. This medicine may not work as well.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Sutent with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Swelling, warmth, numbness, change of color, or pain in a leg or arm.
• Jaw pain.
• Redness or irritation of the palms of hands or soles of feet.
• Very bad and sometimes deadly heart problems like heart failure and heart attack have happened with this medicine. Call your doctor right away if you have a heartbeat that does not feel normal, chest pain or pressure, shortness of breath, a big weight gain, or swelling in the arms or legs.
• Very bad and sometimes deadly blood problems like thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) have happened with Sutent in some people. Call your doctor right away if you feel very tired or weak or have any bruising or bleeding; dark urine or yellow skin or eyes; pale skin; change in the amount of urine passed; change in eyesight; change in strength on 1 side is greater than the other, trouble speaking or thinking, or change in balance; or fever.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about Sutent, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Sutent. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Sutent.

Review Date: October 4, 2017

12.5 mg capsules Hard gelatin capsule with orange cap and orange body, printed with white ink "Pfizer" on the cap and "STN 12.5 mg" on the body.

25 mg capsules Hard gelatin capsule with caramel cap and orange body, printed with white ink "Pfizer" on the cap and "STN 25 mg" on the body.

37.5 mg capsules

Hard gelatin capsule with yellow cap and yellow body, printed with black ink "Pfizer" on the cap and "STN 37.5 mg" on the body.

50 mg capsules

Hard gelatin capsule with caramel top and caramel body, printed with white ink "Pfizer" on the cap and "STN 50 mg" on the body.

None

Gastrointestinal Stromal Tumor

GIST Study A

Study A was a two-arm, international, randomized, double-blind, placebo-controlled trial of Sutent in patients with GIST who had disease progression during prior imatinib mesylate (imatinib) treatment or who were intolerant of imatinib. The objective was to compare Time-to-Tumor Progression (TTP) in patients receiving Sutent plus best supportive care versus patients receiving placebo plus best supportive care. Other objectives included Progression-Free Survival (PFS), Objective Response Rate (ORR), and Overall Survival (OS). Patients were randomized (2:1) to receive either 50 mg Sutent or placebo orally, once daily, on Schedule 4/2 until disease progression or withdrawal from the study for another reason. Treatment was unblinded at the time of disease progression. Patients randomized to placebo were then offered crossover to open-label Sutent, and patients randomized to Sutent were permitted to continue treatment per investigator judgment.

At the time of a pre-specified interim analysis, the intent-to-treat (ITT) population included 312 patients. Two-hundred seven (207) patients were randomized to the Sutent arm, and 105 patients were randomized to the placebo arm. Demographics were comparable between the Sutent and placebo groups with regard to age (69% vs 72% <65 years for Sutent vs. placebo, respectively), gender (Male: 64% vs. 61%), race (White: (88% both arms, Asian: 5% both arms, Black: 4% both arms, remainder not reported), and Performance Status (ECOG 0: 44% vs. 46%, ECOG 1: 55% vs. 52%, and ECOG 2: 1 vs. 2%). Prior treatment included surgery (94% vs. 93%) and radiotherapy (8% vs. 15%). Outcome of prior imatinib treatment was also comparable between arms with intolerance (4% vs. 4%), progression within 6 months of starting treatment (17% vs. 16%), or progression beyond 6 months (78% vs. 80%) balanced.

The planned interim efficacy and safety analysis was performed after 149 TTP events had occurred. There was a statistically significant advantage for Sutent over placebo in TTP, meeting the primary endpoint. Efficacy results are summarized in Table 7 and the Kaplan-Meier curve for TTP is in Figure 1.

Figure 1. Kaplan-Meier Curve of TTP in GIST Study A (Intent-to-Treat Population)

The final ITT population enrolled in the double-blind treatment phase of the study included 243 patients randomized to the Sutent arm and 118 patients randomized to the placebo arm. After the primary endpoint was met at the interim analysis, the study was unblinded, and patients on the placebo arm were offered open-label Sutent treatment. Ninety-nine of the patients initially randomized to placebo crossed over to receive Sutent in the open-label treatment phase. At the protocol specified final analysis of OS, the median OS was 72.7 weeks for the Sutent arm and 64.9 weeks for the placebo arm [HR= 0.876, 95% CI (0.679, 1.129)].

Study B

Study B was an open-label, multi-center, single-arm, dose-escalation study conducted in patients with GIST following progression on or intolerance to imatinib. Following identification of the recommended Phase 2 regimen (50 mg once daily on Schedule 4/2), 55 patients in this study received the 50 mg dose of Sutent on treatment Schedule 4/2. Partial responses were observed in 5 of 55 patients [9.1% PR rate, 95% CI (3.0, 20.0)].

Renal Cell Carcinoma

Treatment-Naïve RCC

A multi-center, international randomized study comparing single-agent Sutent with IFN-α was conducted in patients with treatment-naïve RCC. The objective was to compare Progression-Free Survival (PFS) in patients receiving Sutent versus patients receiving IFN-α. Other endpoints included Objective Response Rate (ORR), Overall Survival (OS) and safety. Seven hundred fifty (750) patients were randomized (1:1) to receive either 50 mg Sutent once daily on Schedule 4/2 or to receive IFN-α administered subcutaneously at 9 MIU three times a week. Patients were treated until disease progression or withdrawal from the study.

The ITT population included 750 patients, 375 randomized to Sutent and 375 randomized to IFN-α. Demographics were comparable between the Sutent and IFN-α groups with regard to age (59% vs. 67% <65 years for Sutent vs. IFN-α, respectively), gender (Male: 71% vs. 72%), race (White: 94% vs. 91%, Asian: 2% vs. 3%, Black: 1% vs. 2%, remainder not reported), and Performance Status (ECOG 0: 62% vs. 61%, ECOG 1: 38% each arm, ECOG 2: 0 vs. 1%). Prior treatment included nephrectomy (91% vs. 89%) and radiotherapy (14% each arm). The most common site of metastases present at screening was the lung (78% vs. 80%, respectively), followed by the lymph nodes (58% vs. 53%, respectively) and bone (30% each arm); the majority of the patients had multiple (2 or more) metastatic sites at baseline (80% vs. 77%, respectively).

There was a statistically significant advantage for Sutent over IFN-α in the endpoint of PFS (see Table 8 and Figure 2). In the pre-specified stratification factors of LDH (>1.5 ULN vs. ≤1.5 ULN), ECOG performance status (0 vs. 1), and prior nephrectomy (yes vs. no), the hazard ratio favored Sutent over IFN-α. The ORR was higher in the Sutent arm (see Table 8).

Figure 2. Kaplan-Meier Curve of PFS in Treatment-Naïve RCC Study (Intent-to-Treat Population)

At the protocol-specified final analysis of OS, the median OS was 114.6 weeks for the Sutent arm and 94.9 weeks for the IFN-α arm [HR= 0.821, 95% CI (0.673, 1.001)]. The median OS for the IFN-α arm includes 25 patients who discontinued IFN-α treatment because of disease progression and crossed over to treatment with Sutent as well as 121 patients (32%) on the IFN-α arm who received post-study cancer treatment with Sutent.

Cytokine-Refractory RCC

The use of single agent Sutent in the treatment of cytokine-refractory RCC was investigated in two single-arm, multi-center studies. All patients enrolled into these studies experienced failure of prior cytokine-based therapy. In Study 1, failure of prior cytokine therapy was based on radiographic evidence of disease progression defined by RECIST or World Health Organization (WHO) criteria during or within 9 months of completion of 1 cytokine therapy treatment (IFN-α, interleukin-2, or IFN-α plus interleukin-2; patients who were treated with IFN-α alone must have received treatment for at least 28 days). In Study 2, failure of prior cytokine therapy was defined as disease progression or unacceptable treatment-related toxicity. The endpoint for both studies was ORR. Duration of Response (DR) was also evaluated.

One hundred six patients (106) were enrolled into Study 1, and 63 patients were enrolled into Study 2. Patients received 50 mg Sutent on Schedule 4/2. Therapy was continued until the patients met withdrawal criteria or had progressive disease. The baseline age, gender, race and ECOG performance statuses of the patients were comparable between Studies 1 and 2. Approximately 86–94% of patients in the two studies were White. Men comprised 65% of the pooled population. The median age was 57 years and ranged from 24 to 87 years in the studies. All patients had an ECOG performance status <2 at the screening visit.

The baseline malignancy and prior treatment history of the patients were comparable between Studies 1 and 2. Across the two studies, 95% of the pooled population of patients had at least some component of clear-cell histology. All patients in Study 1 were required to have a histological clear-cell component. Most patients enrolled in the studies (97% of the pooled population) had undergone nephrectomy; prior nephrectomy was required for patients enrolled in Study 1. All patients had received one previous cytokine regimen. Metastatic disease present at the time of study entry included lung metastases in 81% of patients. Liver metastases were more common in Study 1 (27% vs. 16% in Study 2) and bone metastases were more common in Study 2 (51% vs. 25% in Study 1); 52% of patients in the pooled population had at least 3 metastatic sites. Patients with known brain metastases or leptomeningeal disease were excluded from both studies.

The ORR and DR data from Studies 1 and 2 are provided in Table 9. There were 36 PRs in Study 1 as assessed by a core radiology laboratory for an ORR of 34.0% (95% CI 25.0, 43.8). There were 23 PRs in Study 2 as assessed by the investigators for an ORR of 36.5% (95% CI 24.7, 49.6). The majority (>90%) of objective disease responses were observed during the first four cycles; the latest reported response was observed in Cycle 10. DR data from Study 1 is premature as only 9 of 36 patients (25%) responding to treatment had experienced disease progression or died at the time of the data cutoff.

Pancreatic Neuroendocrine Tumors

The Phase 3 study was a multi-center, international, randomized, double-blind placebo-controlled study of single-agent Sutent conducted in patients with unresectable pNET. Patients were required to have documented RECIST-defined disease progression within the prior 12 months and were randomized (1:1) to receive either 37.5 mg Sutent (n=86) or placebo (n=85) once daily without a scheduled off-treatment period. The primary objective was to compare Progression-Free Survival (PFS) in patients receiving Sutent versus patients receiving placebo. Other endpoints included Overall Survival (OS), Objective Response Rate (ORR), and safety. Use of somatostatin analogs was allowed in the study.

Demographics were comparable between the Sutent and placebo groups. Additionally, 49% of Sutent patients had non-functioning tumors vs 52% of placebo patients, and 92% patients in both arms had liver metastases. A total of 66% of Sutent patients received prior systemic therapy compared with 72% of placebo patients and 35% of Sutent patients had received somatostatin analogs compared with 38% of placebo patients. Patients were treated until disease progression or withdrawal from the study. Upon disease progression, or study closure, patients were offered access to Sutent in a separate extension study.

As recommended by the Independent Data Monitoring Committee, the study was terminated prematurely prior to the pre-specified interim analysis. This may have led to an overestimate of the magnitude of PFS effect. A clinically significant improvement for Sutent over placebo in PFS was seen by both investigator and independent assessment. A hazard ratio favoring Sutent was observed in all subgroups of baseline characteristics evaluated. OS data were not mature at the time of the analysis. There were 9 deaths in the Sutent arm and 21 deaths in the placebo arm. A statistically significant difference in ORR favoring Sutent over placebo was observed. Efficacy results are summarized in Table 10 and the Kaplan-Meier curve for PFS is in Figure 3.

Figure 3. Kaplan-Meier Curve of PFS in the pNET Phase 3 Study

12.5 mg Capsules

Hard gelatin capsule with orange cap and orange body, printed with white ink "Pfizer" on the cap, "STN 12.5 mg" on the body; available in:
Bottles of 28: NDC 0069-0550-38

25 mg Capsules

Hard gelatin capsule with caramel cap and orange body, printed with white ink "Pfizer" on the cap, "STN 25 mg" on the body; available in:
Bottles of 28: NDC 0069-0770-38

37.5 mg Capsules

Hard gelatin capsule with yellow cap and yellow body, printed with black ink "Pfizer" on the cap, "STN 37.5 mg" on the body; available in:
Bottles of 28: NDC 0069-0830-38

50 mg Capsules

Hard gelatin capsule with caramel cap and caramel body, printed with white ink "Pfizer" on the cap, "STN 50 mg" on the body; available in:
Bottles of 28: NDC 0069-0980-38

Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].

Common side effects of Sutent include: oral candidiasis, asthenia, decreased left ventricular ejection fraction, diarrhea, hypokalemia, lymphocytopenia, mucositis, neutropenia, vomiting, and hypertension. Other side effects include: severe hypertension. See below for a comprehensive list of adverse effects.

Take the missed dose as soon as you remember. If you are more than 12 hours late, skip the missed dose. Do not take extra medicine to make up the missed dose.