Afinitor

Name: Afinitor

In case of emergency/overdose

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.

Afinitor Overview

Afinitor is a prescription medication used to treat certain types of cancer in the pancreas, kidney, brain, and breast.

Afinitor belongs to a group of drugs called kinase inhibitors. It works by stopping cancer cells from reproducing and by decreasing blood supply to cancer cells.

Afinitor comes in tablet form and is usually taken once daily with a glass of water.

Common side effects include mouth ulcers, infections, and cough.

Afinitor Precautions

Serious side effects have been reported with Afinitor including the following:

  • Lung or breathing problems that may be severe, and can even lead to death. Tell your doctor right away if you have any of these symptoms:
    • New or worsening cough
    • Shortness of breath
    • Chest pain
    • Difficulty breathing or wheezing
  • Increased risk of developing an infection, such as pneumonia, or a bacterial, fungal or viral infection. Viral infections may include active hepatitis B in people who have had hepatitis B in the past (reactivation). In some people these infections may be severe, and can even lead to death. You may need to be treated as soon as possible.
    • Tell your doctor right away if you have a temperature of 100.5˚F or above, chills, or do not feel well.
    • Symptoms of hepatitis B or infection may include the following:
      • Fever
      • Skin rash
      • Joint pain and inflammation
      • Tiredness
      • Loss of appetite
      • Nausea
      • Pale stool or dark urine
      • Yellowing of the skin
      • Pain in your upper right side
  • Possible increased risk for a type of allergic reaction called angioedema, in people who take an Angiotensin-Converting Enzyme (ACE) inhibitor medicine during treatment with Afinitor. Talk with your healthcare provider before taking Afinitor if you are not sure if you take an ACE inhibitor medicine. Get medical help right away if you have trouble breathing or develop swelling of your tongue, mouth, or throat during treatment with Afinitor. 
  • Kidney failure which may be severe and can even lead to death. Your doctor will likely do tests to check your kidney function before and during your treatment with Afinitor. 
  • Delayed wound healing. Afinitor can cause incisions to heal slowly or not heal well. Call your healthcare provider right away if you have any of the following symptoms:
    • your incision is red, warm or painful
    • blood, fluid, or pus in your incision
    • your incision opens up
    • swelling of your incision

If you have any of the serious side effects listed above, you may need to stop taking Afinitor for a while or use a lower dose. Follow your doctor’s instructions.

Do not take Afinitor if you are allergic to Afinitor or to any of its ingredients. Talk to your doctor before taking this medicine if you are allergic to:

  • sirolimus (Rapamune)
  • temsirolimus (Torisel)

What is everolimus (Afinitor)?

Everolimus is a cancer medicine that interferes with the growth of cancer cells and slows their spread in the body.

The Afinitor brand of everolimus is used to treat certain types of kidney cancer, breast cancer, or brain tumor. Afinitor is also used to treat certain types of advanced or progressive tumors of the stomach, intestines, or pancreas. Afinitor is usually given after other treatments have been tried without success.

Afinitor is also used to treat non-cancerous (benign) tumors of the kidney in people with a certain genetic condition called tuberous sclerosis complex.

This medication guide provides information about the Afinitor brand of everolimus. Zortress is another brand of everolimus used to prevent organ rejection after a kidney transplant.

Everolimus may also be used for purposes not listed in this medication guide.

What should I discuss with my health care provider before taking Afinitor?

You should not use this medicine if you are allergic to everolimus, sirolimus (Rapamune), tacrolimus (Prograf), or temsirolimus (Torisel).

To make sure Afinitor is safe for you, tell your doctor if you have:

  • an active infection, or history of chronic infections;

  • liver disease, or a history of hepatitis B;

  • kidney disease;

  • diabetes or high blood sugar;

  • high cholesterol;

  • if you are scheduled to receive any vaccine; or

  • if you also take an "ACE inhibitor" heart or blood presure medication, such as benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, or trandolapril.

Do not take Afinitor if you are pregnant. It could harm the unborn baby. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 8 weeks after your treatment ends.

Afinitor can affect fertility (your ability to have children), whether you are a man or a woman.

It is not known whether everolimus passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are taking everolimus.

Actions

  • Inhibits mammalian target of rapamycin (mTOR) kinase.1 2 3 4 5 7 8 9 10 11

  • Inhibits antigenic and interleukin (IL-2 and IL-15) stimulated activation and proliferation of T and B lymphocytes.13

  • Binds with high affinity to the intracellular protein FK506 binding protein-12 (FKBP-12), forming a drug-protein complex with mTOR complex 1 (mTORC1 or everolimus:FKBP-12) that binds to and inhibits the activation of mTOR.1 2 5 6 9 10 13

  • Disruption of mTOR reduces the activity of downstream effectors (i.e., S6 ribosomal protein kinase [S6K1], eukaryotic elongation factor 4E-binding protein [4E-BP1]), thereby blocking progression of cells from G1 into S phase and, subsequently, inducing cell growth arrest and apoptosis.4 6 9 10 11 13 S6K1 is a substrate of mTORC1 and phosphorylates the activation domain 1 of the estrogen receptor, resulting in ligand-independent activation of the receptor.1

  • The everolimus:FKBP-12 complex has no effect on calcineurin activity.13

  • Also inhibits expression of hypoxia-inducible factor (e.g., HIF-1α), thereby reducing the expression of vascular endothelial growth factor (VEGF).1 7 9

  • Reduces cell proliferation, angiogenesis, and glucose uptake in vitro and/or in vivo.1 5 10

  • In breast cancer, constitutive activation of the phosphoinositide 3-kinase inhibitor (PI3K)/Akt/mTOR pathway can lead to endocrine resistance.1 Estrogen-dependent and HER2-positive breast cancer cells are sensitive to the inhibitory effects of everolimus in vitro.1 Concomitant use of everolimus with Akt, HER2, or aromatase inhibitors (e.g., anastrozole, exemestane, letrozole) enhances the anti-tumor activity of everolimus in a synergistic manner.1

  • Loss or inactivation of tuberin-sclerosis complexes 1 and 2 (TSC1 and TSC2), 2 of the regulators of mTORC1 signaling, leads to activation of downstream signaling.1 In the genetic disorder tuberous sclerosis, inactivating mutations in the TSC1 or TSC2 gene lead to hematoma formation throughout the body.1 SEGA may develop in patients with tuberous sclerosis.1 17

Uses For Afinitor

Everolimus is used to treat advanced (late-stage) cancers or noncancerous tumors, such as kidney and breast cancer, subependymal giant cell astrocytoma (SEGA, a brain tumor), renal angiomyolipoma (kidney tumor), tuberous sclerosis complex, and neuroendocrine tumors of the pancreas, intestines, and lungs. It is used for patients who have already received other medicines that did not work well or those who will not be treated with surgery.

Everolimus works by interfering with the growth of cancer cells, which are eventually destroyed by the body. Since the growth of normal body cells may also be affected, other unwanted effects will also occur. It belongs to the group of medicines known as antineoplastics (cancer medicines).

Everolimus is also used together with other medicines to lower the body's natural immunity in patients who receive kidney or liver transplants. When a patient receives an organ transplant, the body's white blood cells try to get rid of (reject) the transplanted organ. Everolimus works to suppress the immune system and prevents the white blood cells from getting rid of the transplanted organ.

This medicine is available only with your doctor's prescription.

If OVERDOSE is suspected

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.

Clinical studies

     Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer

A randomized, double-blind, multicenter study of Afinitor plus exemestane versus placebo plus exemestane was conducted in 724 postmenopausal women with estrogen receptor-positive, HER2/neu-negative advanced breast cancer with recurrence or progression following prior therapy with letrozole or anastrozole. Randomization was stratified by documented sensitivity to prior hormonal therapy (yes versus no) and by the presence of visceral metastasis (yes versus no). Sensitivity to prior hormonal therapy was defined as either (1) documented clinical benefit (complete response [CR], partial response [PR], stable disease ≥ 24 weeks) to at least one prior hormonal therapy in the advanced setting or (2) at least 24 months of adjuvant hormonal therapy prior to recurrence. Patients were permitted to have received 0-1 prior lines of chemotherapy for advanced disease.

The primary endpoint for the trial was progression-free survival (PFS) evaluated by Response Evaluation Criteria In Solid Tumors (RECIST), based on investigator (local radiology) assessment. Other endpoints included overall survival (OS), objective response rate (ORR), and safety.

Patients were randomly allocated in a 2:1 ratio to Afinitor 10 mg/day plus exemestane 25 mg/day (n=485) or to placebo plus exemestane 25 mg/day (n=239). The two treatment groups were generally balanced with respect to baseline demographics and disease characteristics. Patients were not permitted to cross over to Afinitor at the time of disease progression.

The median progression-free survival by investigator assessment at the time of the final PFS analysis was 7.8 and 3.2 months in the Afinitor and placebo arms, respectively [HR = 0.45 (95% CI: 0.38, 0.54), one-sided log-rank p <0.0001] (see Table 14 and Figure 1). The results of the PFS analysis based on independent central radiological assessment were consistent with the investigator assessment. PFS results were also consistent across the subgroups of age, race, presence and extent of visceral metastases, and sensitivity to prior hormonal therapy.

Objective response rate was 12.6% (95% CI: 9.8, 15.9) in the Afinitor plus exemestane arm versus 1.7% (95% CI: 0.5, 4.2) in the placebo plus exemestane arm. There were 3 complete responses (0.6%) and 58 partial responses (12.0%) in the Afinitor plus exemestane arm. There were no complete responses and 4 partial responses (1.7%) in the placebo plus exemestane arm.

After a median follow-up of 39.3 months, there was no statistically significant difference in OS between the Afinitor plus exemestane arm and the placebo plus exemestane arm [HR 0.89 (95% CI 0.73, 1.10)].

Table 14: Progression-free Survival Results
a Exemestane (25 mg/day)
b Hazard ratio is obtained from the stratified Cox proportional-hazards model by sensitivity to prior hormonal therapy and presence of visceral metastasis
c p-value is obtained from the one-sided log-rank test stratified by sensitivity to prior hormonal therapy and presence of visceral metastasis
d Objective response rate = proportion of patients with CR or PR
e not applicable
Analysis Afinitor
+ exemestanea
N = 485
Placebo
+ exemestanea
N = 239
Hazard ratio P-value
Median progression-free survival (months, 95% CI)
Investigator radiological review 7.8
(6.9 to 8.5)
3.2
(2.8 to 4.1)
0.45b
(0.38 to 0.54)
<0.0001c
Independent radiological review 11.0
(9.7 to 15.0)
4.1
(2.9 to 5.6)
0.38b
(0.3 to 0.5)
<0.0001c
Best overall response (%, 95% CI)
Objective response rate (ORR)d 12.6%
(9.8 to 15.9)
1.7%
(0.5 to 4.2)
n/ae

Figure 1: Kaplan-Meier Progression-free Survival Curves (Investigator Radiological Review)

     Advanced Neuroendocrine Tumors

Locally Advanced or Metastatic Advanced Pancreatic Neuroendocrine Tumors (PNET)

A randomized, double-blind, multi-center trial of Afinitor plus best supportive care (BSC) versus placebo plus BSC was conducted in patients with locally advanced or metastatic advanced pancreatic neuroendocrine tumors (PNET) and disease progression within the prior 12 months. Patients were stratified by prior cytotoxic chemotherapy (yes versus no) and by WHO performance status (0 versus 1 and 2). Treatment with somatostatin analogs was allowed as part of BSC. The primary endpoint for the trial was progression-free survival (PFS) evaluated by RECIST (Response Evaluation Criteria in Solid Tumors). After documented radiological progression, patients could be unblinded by the investigator; those randomized to placebo were then able to receive open-label Afinitor. Other endpoints included safety, objective response rate [ORR (complete response (CR) or partial response (PR)], response duration, and overall survival.

Patients were randomized 1:1 to receive either Afinitor 10 mg/day (n=207) or placebo (n=203). Demographics were well balanced (median age 58 years, 55% male, 79% Caucasian). Of the 203 patients randomized to best supportive care, 172 patients (85%) received Afinitor following documented radiologic progression.

The trial demonstrated a statistically significant improvement in PFS (median 11.0 months versus 4.6 months), resulting in a 65% risk reduction in investigator-determined PFS (HR 0.35; 95%CI: 0.27 to 0.45; p<0.001) (see Table 15 and Figure 2). PFS improvement was observed across all patient subgroups, irrespective of prior somatostatin analog use. The PFS results by investigator radiological review, central radiological review and adjudicated radiological review are shown below in Table 15.

Table 15: Progression-free Survival Results
a includes adjudication for discrepant assessments between investigator radiological review and central radiological review
Analysis N
Afinitor
N=207
Placebo
N=203
Hazard Ratio (95%CI) p-value
410 Median progression-free survival (months) (95% CI)
Investigator radiological review 11.0
(8.4 to 13.9)
4.6
(3.1 to 5.4)
0.35
(0.27 to 0.45)
<0.001
Central radiological review 13.7
(11.2 to 18.8)
5.7
(5.4 to 8.3)
0.38
(0.28 to 0.51)
<0.001
Adjudicated radiological reviewa 11.4
(10.8 to 14.8)
5.4
(4.3 to 5.6)
0.34
(0.26 to 0.44)
<0.001

Figure 2: Kaplan-Meier Investigator-Determined Progression-free Survival Curves

Investigator-determined response rate was 4.8% in the Afinitor arm and there were no complete responses. Overall survival was not statistically significantly different between study arms [HR=0.94 (95% CI 0.73 to 1.20); p=0.30].

Unresectable, Locally Advanced or Metastatic, Well-Differentiated, Non-Functional Neuroendocrine Tumors of Gastrointestinal or Lung Origin

A randomized, double-blind, multicenter study of Afinitor plus best supportive care (BSC) versus placebo plus best supportive care was conducted in patients with unresectable, locally advanced or metastatic, well differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (excluding pancreatic) or lung origin. The study required that patients had well-differentiated (low or intermediate grade) histology, no prior or current history of carcinoid symptoms, and evidence of disease progression within 6 months prior to randomization. Patients were randomized 2:1 to receive either Afinitor 10 mg/day or placebo, and stratified by prior somatostatin analog (SSA) use (yes versus no), tumor origin and WHO performance status (0 versus 1).

The major efficacy outcome measure was progression-free survival (PFS) based on independent radiological assessment evaluated by RECIST. Additional efficacy outcome measures were overall survival and overall response rate. A total of 302 patients were randomized, 205 to the Afinitor arm and 97 to the placebo arm. The median age was 63 years (range 22 to 86); 47% were male; 76% were White; 74% had WHO performance status (PS) 0 and 26% had WHO PS 1. The most common primary sites of tumor were lung (30%), ileum (24%), and rectum (13%).

The study demonstrated a statistically significant improvement in PFS per independent radiological review (see Table 16 and Figure 3). There was no statistically significant difference in OS at the planned interim analysis.

Table 16: Efficacy Results
1. Hazard ratio is obtained from the stratified Cox model.
2. p-value is obtained from the stratified log-rank test.
Afinitor
N=205
Placebo
N=97
Progression-Free Survival
Number of Events 113 (55%) 65 (67%)
     Progressive Disease 104 (51%) 60 (62%)
     Death 9 (4%) 5 (5%)
Median PFS in months (95% CI) 11.0 (9.2, 13.3) 3.9 (3.6, 7.4)
Hazard Ratio (95%CI)1 0.48 (0.35, 0.67)
p-value2 <0.001
Overall Response Rate 2% 1%

Figure 3: Kaplan-Meier Progression-free Survival Curves

Lack of Efficacy in Locally Advanced or Metastatic Functional Carcinoid Tumors

The safety and effectiveness of Afinitor in patients with locally advanced or metastatic functional carcinoid tumors have not been demonstrated. In a randomized (1:1), double-blind, multi-center trial in 429 patients with carcinoid tumors, Afinitor plus depot octreotide (Sandostatin LAR®) was compared to placebo plus depot octreotide. After documented radiological progression, patients on the placebo arm could receive Afinitor; of those randomized to placebo, 143 (67%) patients received open-label Afinitor plus depot octreotide. The study did not meet its primary efficacy endpoint of a statistically significant improvement in PFS and the final analysis of OS favored the placebo plus depot octreotide arm.

     Advanced Renal Cell Carcinoma

An international, multi-center, randomized, double-blind trial comparing Afinitor 10 mg daily and placebo, both in conjunction with best supportive care, was conducted in patients with metastatic RCC whose disease had progressed despite prior treatment with sunitinib, sorafenib, or both sequentially. Prior therapy with bevacizumab, interleukin 2, or interferon-α was also permitted. Randomization was stratified according to prognostic score1 and prior anticancer therapy.

Progression-free survival (PFS), documented using Response Evaluation Criteria in Solid Tumors (RECIST) was assessed via a blinded, independent, central radiologic review. After documented radiological progression, patients could be unblinded by the investigator: those randomized to placebo were then able to receive open-label Afinitor 10 mg daily. 

In total, 416 patients were randomized 2:1 to receive Afinitor (n=277) or placebo (n=139). Demographics were well balanced between the 2 arms (median age 61 years; 77% male, 88% Caucasian, 74% received prior sunitinib or sorafenib, and 26% received both sequentially).

Afinitor was superior to placebo for PFS (see Table 17 and Figure 4). The treatment effect was similar across prognostic scores and prior sorafenib and/or sunitinib. Final overall survival (OS) results yield a hazard ratio of 0.90 (95% CI: 0.71 to 1.14), with no statistically significant difference between the 2 treatment groups. Planned cross-over from placebo due to disease progression to open label Afinitor occurred in 111 of the 139 patients (79.9%) and may have confounded the OS benefit.

Table 17: Efficacy Results by Central Radiologic Review
a Log-rank test stratified by prognostic score.
b Not applicable.
Afinitor
N=277
Placebo
N=139
Hazard Ratio
(95% CI)
p-value a
Median Progression-free Survival
(95% CI)
4.9 months
(4.0 to 5.5)
1.9 months
(1.8 to 1.9)
0.33
(0.25 to 0.43)
<0.0001
Objective Response Rate 2% 0% n/a b n/a b

Figure 4: Kaplan-Meier Progression-free Survival Curves

     Renal Angiomyolipoma with Tuberous Sclerosis Complex

A randomized (2:1), double-blind, placebo-controlled trial of Afinitor was conducted in 118 patients with renal angiomyolipoma as a feature of TSC (n=113) or sporadic lymphangioleiomyomatosis (n=5).

The key eligibility requirements for this trial were at least one angiomyolipoma of ≥3 cm in longest diameter on CT/MRI based on local radiology assessment, no immediate indication for surgery, and age ≥18 years. Patients received daily oral Afinitor 10 mg or matching placebo until disease progression or unacceptable toxicity. CT or MRI scans for disease assessment were obtained at baseline, 12, 24, and 48 weeks and annually thereafter. Clinical and photographic assessment of skin lesions were conducted at baseline and every 12 weeks thereafter until treatment discontinuation. The major efficacy outcome measure was angiomyolipoma response rate based on independent central radiology review, which was defined as a ≥50% reduction in angiomyolipoma volume, absence of new angiomyolipoma lesion ≥1 cm, absence of kidney volume increase ≥20%, and no angiomyolipoma related bleeding of ≥ Grade 2. Key supportive efficacy outcome measures were time to angiomyolipoma progression and skin lesion response rate. The primary analyses of efficacy outcome measures were limited to the blinded treatment period and conducted 6 months after the last patient was randomized. The comparative angiomyolipoma response rate analysis was stratified by use of enzyme-inducing antiepileptic drugs (EIAEDs) at randomization (yes versus no).

Of the 118 patients enrolled, 79 were randomized to Afinitor and 39 to placebo. The median age was 31 years (range 18 to 61 years), 34% were male, and 89% were Caucasian. At baseline, 17% of patients were receiving EIAEDs. On central radiology review at baseline, 92% of patients had at least 1 angiomyolipoma of ≥3 cm in longest diameter, 29% had angiomyolipomas ≥8 cm, 78% had bilateral angiomyolipomas, and 97% had skin lesions. The median values for the sum of all target renal angiomyolipoma lesions at baseline were 85 cm3 (range 9 to 1612 cm3) and 120 cm3 (range 3 to 4520 cm3) in the Afinitor and placebo arms respectively. Forty-six (39%) patients had prior renal embolization or nephrectomy. The median duration of follow-up was 8.3 months (range 0.7 to 24.8 months) at the time of the primary analysis.

The renal angiomyolipoma response rate was statistically significantly higher in Afinitor-treated patients; there were 33 (41.8%) patients with angiomyolipoma responses in the Afinitor arm as compared to none in the placebo arm. Results are displayed in Table 18. The median response duration was 5.3+ months (range 2.3+ to 19.6+ months).

There were 3 patients in the Afinitor arm and 8 patients in the placebo arm with documented angiomyolipoma progression by central radiologic review (defined as a ≥25% increase from nadir in the sum of angiomyolipoma target lesion volumes to a value greater than baseline, appearance of a new angiomyolipoma ≥1.0 cm in longest diameter, an increase in renal volume ≥ 20% from nadir for either kidney and to a value greater than baseline, or Grade ≥2 angiomyolipoma-related bleeding). The time to angiomyolipoma progression was statistically significantly longer in the Afinitor arm (HR 0.08 [95% CI: 0.02, 0.37]; p <0.0001).

Table 18: Angiomyolipoma Response
a Per independent central radiology review
Afinitor Placebo p-value
N=79 N=39
Primary analysis
      Angiomyolipoma response ratea - % 41.8 0 <0.0001
      95% CI (30.8, 53.4) (0.0, 9.0)

Skin lesion response rates were assessed by local investigators for 77 patients in the Afinitor arm and 37 patients in the placebo arm who presented with skin lesions at study entry. The skin lesion response rate was statistically significantly higher in the Afinitor arm (26% versus 0, p=0.0011); all skin lesion responses were partial responses, defined as visual improvement in 50%-99% of all skin lesions durable for at least 8 weeks (Physician's Global Assessment of Clinical Condition).

Patients randomized to placebo were permitted to receive Afinitor at the time of angiomyolipoma progression or after the time of the primary analysis. After the primary analysis, patients treated with Afinitor underwent additional follow-up CT or MRI scans to assess tumor status until discontinuation of treatment or completion of 4 years of follow-up after the last patient was randomized. A total of 112 patients (79 randomized to Afinitor and 33 randomized to placebo) received at least one dose of Afinitor. The median duration of Afinitor treatment was 3.9 years (range: 0.5 months to 5.3 years) and the median duration of follow-up was 3.9 years (range: 0.9 months to 5.4 years). During the follow-up period after the primary analysis, 32 patients (in addition to the 33 patients identified at the time of the primary analysis) had an angiomyolipoma response based upon independent central radiology review. Among the 65 responders out of 112 patients, the median time to angiomyolipoma response was 2.9 months (range: 2.6 to 33.8 months). Sixteen of the 112 patients treated with Afinitor had angiomyolipoma progression by the end of the follow-up period. No patient underwent a nephrectomy for angiomyolipoma progression and one patient underwent renal embolization while treated with Afinitor.

     Subependymal Giant Cell Astrocytoma with Tuberous Sclerosis Complex

Study 1 was a randomized (2:1), double-blind, placebo-controlled trial of Afinitor conducted in 117 pediatric and adult patients with subependymal giant cell astrocytoma (SEGA) and tuberous sclerosis complex (TSC). Eligible patients had at least one SEGA lesion ≥1.0 cm in longest diameter on MRI based on local radiology assessment and one or more of the following: serial radiological evidence of SEGA growth, a new SEGA lesion ≥1 cm in longest diameter, or new or worsening hydrocephalus. Patients randomized to the treatment arm received Afinitor tablets at a starting dose of 4.5 mg/m2 daily, with subsequent dose adjustments as needed to achieve and maintain everolimus trough concentrations of 5 to 15 ng/mL as tolerated. Afinitor/matched placebo treatment continued until disease progression or unacceptable toxicity. MRI scans for disease assessment were obtained at baseline, 12, 24, and 48 weeks, and annually thereafter.

The main efficacy outcome measure was SEGA response rate based on independent central radiology review. SEGA response was defined as a ≥ 50% reduction in the sum of SEGA volume relative to baseline, in the absence of unequivocal worsening of non-target SEGA lesions, a new SEGA lesion ≥ 1 cm, and new or worsening hydrocephalus. The primary analysis of SEGA response rate was limited to the blinded treatment period and conducted 6 months after the last patient was randomized. The analysis of SEGA response rate was stratified by use of enzyme-inducing antiepileptic drugs (EIAEDs) at randomization (yes versus no).

Of the 117 patients enrolled, 78 were randomized to Afinitor and 39 to placebo. The median age was 9.5 years (range 0.8 to 26 years; 69% were 3 to < 18 years at enrollment; 17% were <3 years at enrollment), 57% were male, and 93% were Caucasian. At baseline, 18% of patients were receiving EIAEDs. Based on central radiology review at baseline, 98% of patients had at least one SEGA lesion ≥1.0 cm in longest diameter, 79% had bilateral SEGAs, 43% had ≥2 target SEGA lesions, 26% had growth in or into the inferior surface of the ventricle, 9% had evidence of growth beyond the subependymal tissue adjacent to the ventricle, and 7% had radiographic evidence of hydrocephalus. The median values for the sum of all target SEGA lesions at baseline were 1.63 cm3 (range 0.18 to 25.15 cm3) and 1.30 cm3 (range 0.32 to 9.75 cm3) in the Afinitor and placebo arms respectively. Eight (7%) patients had prior SEGA-related surgery. The median duration of follow-up was 8.4 months (range 4.6 to 17.2 months) at the time of primary analysis.

The SEGA response rate was statistically significantly higher in Afinitor-treated patients. There were 27 (35%) patients with SEGA responses in the Afinitor arm and no SEGA responses in the placebo arm. Results are displayed in Table 19. At the time of the primary analysis, all SEGA responses were ongoing and the median duration of response was 5.3 months (range 2.1 to 8.4 months).

With a median follow-up of 8.4 months, SEGA progression was detected in 6 of 39 (15.4%) patients randomized to receive placebo and none of the 78 patients randomized to receive Afinitor. No patient in either treatment arm required surgical intervention.

Table 19: SEGA Response
a Per independent central radiology review
Afinitor Placebo p-value
N=78 N=39
Primary analysis
      SEGA response ratea - (%) 35 0 <0.0001
      95% CI 24, 46 0, 9

Patients randomized to placebo were permitted to receive Afinitor at the time of SEGA progression or after the primary analysis, whichever occurred first. After the primary analysis, patients treated with Afinitor underwent additional follow-up MRI scans to assess tumor status until discontinuation of treatment or completion of 4 years of follow-up after the last patient was randomized. A total of 111 patients (78 patients randomized to Afinitor and 33 patients randomized to placebo) received at least one dose of Afinitor. Median duration of Afinitor treatment and follow-up was 3.9 years (range: 0.2 to 4.9 years).

By four years after the last patient was enrolled, a total of 64 of the 111 patients treated with Afinitor had a ≥50% reduction in SEGA volume relative to baseline, including 27 patients identified at the time of the primary analysis and 37 patients with a SEGA response after the primary analysis. The median time to SEGA response was 5.3 months (range: 2.5 to 33.1 months). Thirteen of the 111 patients treated with Afinitor had documented disease progression by the end of the follow-up period and no patient required surgical intervention for SEGA during the course of the study.

Study 2 was an open-label, single-arm trial conducted to evaluate the safety and antitumor activity of Afinitor 3.0 mg/m2/orally once daily in patients with SEGA and TSC. Serial radiological evidence of SEGA growth was required for entry. Tumor assessments were performed every 6 months for 60 months after the last patient was enrolled or disease progression, whichever occurred earlier. The major efficacy outcome measure was the reduction in volume of the largest SEGA lesion with 6 months of treatment, as assessed via independent central radiology review. Progression was defined as an increase in volume of the largest SEGA lesion over baseline that was ≥25% over the nadir observed on study.

Study 2 enrolled 28 patients who received Afinitor for a median duration of 5.7 years (range: 5 months to 6.9 years); 23 of 28 patients (82%) remained on Afinitor for at least 5 years. Across the study population, the median age was 11 years (range 3-34), 61% male, 86% Caucasian.

At the primary analysis, 9 of 28 patients [32% (95% CI: 16% to 52%)] had an objective response at 6 months, defined as at least a 50% decrease in volume of the largest SEGA lesion. At the completion of the study, the median duration of durable response was 12 months (range 3 months to 6.3 years).

By 60 months after the last patient was enrolled, 11% of patients (3/28) had documented disease progression. No patient developed a new SEGA lesion while on Afinitor. Nine additional patients were identified as having a >50% volumetric reduction in their largest SEGA lesion between 1 to 4 years after initiating Afinitor including 3 patients who had surgical resection with subsequent regrowth prior to receiving Afinitor.

What is Afinitor?

Afinitor (everolimus) is a cancer medicine that interferes with the growth of cancer cells and slows their spread in the body.

Afinitor is used to treat certain types of kidney cancer, breast cancer, or brain tumor. Everolimus is usually given after other treatments have been tried without success.

Afinitor is also used to treat certain types of advanced or progressive tumors of the stomach, intestines, or pancreas.

Afinitor is also used to treat non-cancerous (benign) tumors of the kidney in people with a certain genetic condition called tuberous sclerosis complex.

Zortress is another brand of everolimus used to prevent organ rejection after a kidney transplant.

What should I avoid while taking Afinitor?

If you develop mouth sores or ulcers, avoid using mouthwashes or applying medicines that contain alcohol, peroxide, iodine, or thyme.

Do not receive a "live" vaccine while using Afinitor, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Everolimus can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Grapefruit and grapefruit juice may interact with everolimus and lead to unwanted side effects. Avoid the use of grapefruit products while taking Afinitor.

In Summary

Common side effects of Afinitor include: decreased hemoglobin, increased serum glucose, lymphocytopenia, and stomatitis. Other side effects include: pneumonitis, pneumonia, and increased hdl cholesterol. See below for a comprehensive list of adverse effects.

Everolimus Breastfeeding Warnings

Breastfeeding is not recommended during use of this drug. Excreted into human milk: Unknown Excreted into animal milk: Yes Comments: The effects in the nursing infant are unknown.

Animal studies have shown that this drug and/or its metabolites pass readily into milk. The concentration in the milk was 3.5 times greater than the maternal serum.

Highlights for Afinitor

Afinitor is an oral drug used to treat certain types of breast cancer, kidney cancer, and brain tumors. It’s also used to treat tumors of the pancreas and noncancerous kidney tumors.

Afinitor comes as a tablet you take by mouth.

Afinitor is a brand name for the drug everolimus. This drug also comes in a tablet for suspension as Afinitor Disperz. This drug is not available as a generic drug.

IMPORTANT INFORMATION
  • Risk of infections See Details

  • Allergic reaction See Details

What is Afinitor?

This drug is a prescription drug. It comes as a tablet you take by mouth.

Afinitor is a brand name for the drug everolimus. It isn’t available as a generic drug.

This drug is used as part of a combination therapy when it’s used to treat advanced breast cancer (hormone receptor-positive, HER2-negative breast cancer). That means you need to take it with other drugs.

Why it's used

This drug is used to treat certain types of cancers and tumors. These include:

  • Advanced breast cancer. It’s used to treat hormone receptor-positive, HER2-negative breast cancer in postmenopausal women.
  • Advanced pancreatic neuroendocrine tumors (PNET)
  • Renal cell carcinoma (advanced kidney cancer)
  • Kidney tumors in adults with a genetic condition called tuberous sclerosis complex (TSC)
  • Brain tumors called subependymal giant cell astrocytomas (SEGAs) in adults and children with tuberous sclerosis complex (TSC)

This drug is used when these conditions haven’t responded to other treatments or when the tumors can’t be surgically removed.

How it works

This drug belongs to a class of drugs called mammalian target of rapamycin (mTOR) kinase inhibitors. A class of drugs refers to medications that work in a similar way. These drugs are often used to treat similar conditions.

This drug works by interfering with the action of certain enzymes in your body called mTOR kinases. These enzymes help both healthy cells and cancer cells to grow and multiply. When kinases don’t act normally, they make cancers and tumors grow out of control. This drug inhibits mTOR kinases and stops the tumor or cancer from growing. This prevents the spread of the cancer or tumor in your body.

Afinitor Side Effects

More common side effects

  • The more common side effects of Afinitor in people with breast cancer, pancreatic tumors, and kidney cancer include:

    • mouth sores
    • infections
    • weakness or tiredness
    • cough
    • shortness of breath
    • diarrhea
    • constipation
    • skin rash or dry, itchy skin
    • nausea
    • vomiting
    • fever
    • loss of appetite
    • weight loss
    • swelling of your arms, hands, feet, ankles, face, or other parts of your body
    • metallic taste in your mouth
    • dry mouth
    • inflammation of the lining of your digestive system
    • headache
    • nosebleeds
    • pain in your arms, legs, mouth, throat, back, or joints
    • high blood sugar levels
    • high blood pressure
    • trouble sleeping
    • hair loss
    • muscle spasms
    • dizziness
    • nail disorders

  • The more common side effects of Afinitor in people with subependymal giant cell astrocytoma (SEGA) brain tumors or kidney tumors include:

    • mouth sores
    • infections
    • nausea
    • vomiting
    • diarrhea
    • constipation
    • swelling of your hands, arms, legs, and feet
    • joint pain
    • cough
    • skin problems, such as rash, acne, or dry skin
    • fever
    • tiredness
    • anxiety, aggression, and other abnormal behavior
    • missed menstrual periods
    • low levels of red blood cells, white blood cells, or platelets
    • high cholesterol levels
    • high blood sugar levels
    • low blood phosphate levels

If these effects are mild, they may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist.

Serious side effects

Call your doctor right away if you have serious side effects. Call 9-1-1 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

  • Lung or breathing problems, such as pneumonitis and pulmonary hypertension. Symptoms can include:

    • cough that’s new gets worse
    • shortness of breath
    • chest pain
    • wheezing or trouble breathing
    • fast heart rate
  • Infections. Symptoms can include:

    • fever greater than 100.5°F
    • chills
    • skin rash
    • joint pain and swelling
    • tiredness
    • loss of appetite
    • nausea
    • pale stools
    • dark urine
    • yellowing of your skin
    • pain in the upper right side of your abdomen
  • Kidney failure. Symptoms can include:

    • fever
    • weakness
    • tiredness
    • producing little to no urine
    • swelling of parts of your body
  • Wounds that heal slowly or don’t heal well. Symptoms can include:

    • wound that’s red, warm, or painful
    • blood, fluid, or pus in the wound
    • open wounds
    • swelling of the wound
Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare provider who knows your medical history.
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