Frequent adverse events

Clinical trial safety data

IBRANCE has a consistent and manageable safety profile in combination with endocrine therapy1-4

The most frequent (≥20%) AEs of any grade observed across the PALOMA clinical trial programme were:1*

  • Neutropenia: 716 (82.1%)
  • Infections: 516 (59.2%)
  • Leukopenia: 424 (48.6%)
  • Fatigue: 362 (41.5%)
  • Nausea: 314 (36.0%)
  • Stomatitis: 264 (30.3%)
  • Anaemia: 258 (29.6%)
  • Diarrhoea: 238 (27.3%)
  • Alopecia: 258 (29.6%)

In all grades: 

  • Febrile neutropenia: 12 (1.4%)
  • ILD/pneumonitis: 12 (1.4%)

For the most up-to-date safety information, please see the IBRANCE Summary of Product Characteristics.1

ILD/pneumonitis

ILD/pneumonitis includes any reported PTs that are part of the Standardized MedDra Query Interstitial Lung Disease (narrow). Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g. hypoxia, cough, dyspneoa). In patients who have new or worsening respiratory symptoms and are suspected to have developed ILD/pneumonitis, interrupt IBRANCE immediately and evaluate the patient. Permanently discontinue IBRANCE in patients with severe ILD or pneumonitis.1

Overall AEs reported with IBRANCE1*

 

Adapted from IBRANCE Summary of Product Characteristics1.

For the most up-to-date safety information, please refer to the full IBRANCE Summary of Product Characteristics

Long-term safety

No new safety signals were observed after an additional long-term follow-up of 37.6 months.8

Adverse event management tips

To help you prevent, identify and manage possible adverse events with IBRANCE, select an adverse event from the list below for useful management tips for both you and your patients:

Neutropenia

Advice for healthcare professionals

  • Proactively monitor full blood count, especially in the first two cycles, as neutropenia can be effectively managed by dose modification (i.e. temporary dose interruptions, cycle delays, and/or reductions)1
  • See the haematologic toxicities management algorithm in the IBRANCE Dosing Guide

Advice to give your patients

  • Promptly report any signs/symptoms of infection, such as fever (temperature ≥38°C) or chills7
  • Check for fever at least once a day or as often as their healthcare professional recommends8
  • Avoid crowded places and do not visit people with infections, coughs or fevers, especially when white blood counts are low7
  • Maintain good hygiene; for example, patients should:8
    • Wash their hands often with soap and water, and carry hand sanitiser for times when they are unable to wash their hands
    • Wash cuts and scrapes with warm water, soap and an antiseptic until they have healed
    • Brush their teeth after meals and before they go to bed with a soft toothbrush, and use a mouth rinse that does not contain alcohol
  • Use sanitising wipes to clean surfaces and items that they touch8
  • Avoid anything that can cause cuts, scrapes or other breaks in the skin7
  • Wash raw fruit and vegetables well before eating them8
  • Do not eat raw or undercooked fish, seafood, meat, chicken or eggs, as these may contain bacteria that can cause infection7

Anaemia

Advice for healthcare professionals

  • Treat underlying anaemia as appropriate
  • IBRANCE-induced anaemia is managed with dose delays and adjustments (i.e. temporary dose interruptions, cycle delays, and/or reductions)1
    • See the haematologic toxicities management algorithm in the IBRANCE® (palbociclib) Dosing Guide)
  • Standard-of-care treatment should be considered

Advice to give your patients

  • Immediately report any dizziness, shortness of breath or tiredness8
  • Eat a well-balanced diet8
  • Balance rest and activities7
  • Stand up slowly, to avoid feeling dizzy; if getting up from lying down, sit for a minute before standing up8
  • Plan important activities for when they have the most energy7
  • Tell their doctor if unable to get around as they once were used to7
  • Get plenty of rest; patients should try to sleep at least 8 hours each night and might also want to take 1–2 short naps (1 hour or less) during the day8

Thrombocytopenia

Advice for healthcare professionals

  • Thrombocytopenia is manageable with dose delays and adjustments (i.e. temporary dose interruptions, cycle delays, and/or reductions)1
    • See the haematologic toxicities management algorithm in the IBRANCE Dosing Guide

Advice to give your patients

  • Immediately report bleeding or bruising more easily8
  • Avoid activities that might lead to injury8
  • Protect skin from cuts, scrapes, and sharp objects8 — e.g. use an electric razor, not a blade, for shaving8
  • Avoid medications that interfere with platelets being able to form clots e.g. NSAIDs8

Infection

Advice for healthcare professionals

  • Treat infections and symptoms of infection with standard-of-care treatment1
    • Including an anti-infective for bacterial infections as appropriate

Advice to give your patients

  • Promptly report any signs or symptoms of infection1
    • Such as fever or chills
  • Maintain good hygiene8
    • e.g. patients should wash their hands often
  • Wash vegetables, salads and fruit well8
  • Avoid crowded places, and do not visit people with infections, coughs, or fevers7

Alopecia (hair thinning)

Advice to give your patients7

  • Use gentle hair products, such as baby shampoos
  • Be gentle when brushing and washing hair, and use a wide-toothed comb
  • Avoid too much hair brushing or pulling (braids or ponytails)
  • Avoid using hairdryers, curling tongs and curlers and, ideally, pat your hair dry
  • Wear a hat or scarf outside to keep warm
  • Wear cotton items on the scalp because they tend to stay on better than nylon or polyester
  • Use sunscreen, sunblock or a hat to protect the scalp from the sun
  • Wear a hairnet while sleeping, or sleep on a satin pillowcase
  • Avoid perms and dyes for the first few months of new hair growth, to prevent breakage

Diarrhoea

Advice for heathcare professionals

  • Treat IBRANCE-related diarrhoea with an anti-diarrhoeal as appropriate

Advice to give your patients7

  • Drink plenty of clear liquid to replace lost fluids
    • e.g. water, weak tea, apple juice, peach or apricot nectar, clear broth
  • Eat small, frequent meals instead of three large ones
  • Avoid greasy foods, bran, raw fruits and vegetables, caffeine, very hot or spicy foods and milk or milk products
  • Eat foods high in potassium
    • e.g. bananas, potatoes, apricots
  • Don’t drink alcohol or use tobacco
  • When the diarrhoea starts to improve, try eating small amounts of foods that are easy to digest
    • e.g. rice, bananas, applesauce, yoghurt, mashed potatoes, low fat cottage cheese and dry toast

Nausea

Advice for heathcare professionals

  • If necessary, nausea and vomiting can be treated with an anti-emetic as appropriate7

Advice to give your patients

  • Drink plenty of clear liquid to replace lost fluids
    • e.g. water, weak tea, apple juice, peach or apricot nectar, clear broth
  • Eat small, frequent meals instead of three large ones
  • Avoid greasy foods, bran, raw fruits and vegetables, caffeine, very hot or spicy foods and milk or milk products
  • Eat foods high in potassium
    • e.g. bananas, potatoes, apricots
  • Don’t drink alcohol or use tobacco
  • When the diarrhoea starts to improve, try eating small amounts of foods that are easy to digest
    • e.g. rice, bananas, applesauce, yoghurt, mashed potatoes, low fat cottage cheese and dry toast

Fatigue

Advice to give your patients7-9

  • Plan your daily routine to make sure you are getting enough rest and activity
  • Try doing light exercise each day, as this can give you more energy
  • Take short rests or breaks
  • Don’t push yourself too hard; rest when you begin to feel tired
  • Eat a well-balanced diet and drink plenty of fluids
    • Sometimes tiredness and weakness can be caused by dehydration
  • Plan important activities for when you have the most energy
  • Ask others to help with more strenuous activities, such as chores
  • Do things that are relaxing, such as listening to music or reading
  • Support groups may be able to help you manage stress and work through things that are making you tired

If you would like more detailed information on the incidence, classification and characterisation of the above adverse events, please ask a Pfizer representative for a copy of the “Practical guide to treatment with IBRANCE”.

*Based on pooled data from 872 patients who received IBRANCE in combination with ET (n=527 in combination with letrozole and n=345 in combination with fulvestrant) in three randomised clinical studies in HR+/HER2- advanced or mBC1.

†Preferred terms (PTs) are listed according to MedDRA 17.1. INFECTIONS includes all PTs that are part of the System Organ Class Infections and infestations. NEUTROPENIA includes the following PTs: Neutropenia; Neutrophil count decreased. LEUKOPENIA includes the following PTs: Leukopenia; White blood cell count decreased. ANAEMIA includes the following PTs: Anaemia, Haemoglobin decreased, Haematocrit decreased. THROMBOCYTOPENIA includes the following PTs: Thrombocytopenia, Platelet count decreased. STOMATITIS includes the following PTs: Aphthous stomatitis, Cheilitis, Glossitis, Glossodynia, Mouth ulceration, Mucosa! inflammation, Oral pain, Oropharyngeal discomfort, Oropharyngeal pain, Stomatitis. RASH includes the following PTs: Rash, Rash maculo-papular, Rash pruritic, Rash erythematous, Rash papular, Dermatitis, Dermatitis acneiform, Toxic skin eruption1.

Adverse Drug Reaction (ADR) identified post-marketing. ILD/pneumonitis includes any reported PTs that are part of the Standardized MedDRA Query Interstitial Lung Disease (narrow).1

AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; mBC, metastatic breast cancer; MedDRA, Medical  dictionary for regulatory activities; NA, not applicable.

For the most up-to-date safety information, please refer to the full IBRANCE Summary of Product Characteristics

References:

  1. IBRANCE® Summary of Product Characteristics.
  2. Rugo HS, et al. Breast Cancer Res Treat. 2019;174:719–29.
  3. Finn RS, et al. N Engl J Med. 2016;375:1925–36.
  4. Cristofanilli M. et al. Lancet Oncol. 2016;17:425–39.
  5. Verma S. et al. Oncologist. 2016;21:1165–75.
  6. Turner NC, et al. N Engl J Med. 2018;379:1926–36.
  7. American Cancer Society. Caring for the patient with cancer at home: a guide for patients and families. https://www.cancer.org/treatment/treatments-and-side-effects/physical-si... accessed February 2018.
  8. National Cancer Institute. US Department of Health and Human Services. Chemotherapy and you. NIH publication 11–7156. Revised May 2007. Printed June 2011. https://www.cancer.gov/publications/patient-education/chemotherapy-and-y... accessed January 2018.
  9. Cancer Research UK_Combined_blood_hair loss_fatigue; Cancer Research UK. Your blood, bone marrow and cancer drugs. https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/side-effects/your-blood-and-bone-marrow Cancer Research UK. Hair loss, thinning and cancer drugs. http://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/side-effects/hair-loss-and-thinning?_ga=2.51758560.816131623.1509642215-582622013.1509642215; accessed January 2018. Cancer Research UK. Fatigue and cancer drugs. http://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/side-effects/fatigue?_ga=2.47877742.816131623.1509642215-582622013.1509642215; accessed January 2018.

PP-IBR-GBR-2124. December 2019

Haematologic toxicities

IBRANCE haematologic adverse events, including neutropenia, can be managed through scheduled full blood count (FBC) monitoring and dose modifications (temporary dose interruptions, cycle delays, and/or reductions)1 .

Check that patients have a baseline ANC ≥1 x 109 cells/L and that platelet counts are ≥ 50 x 109 cells/L before starting treatment with IBRANCE. IBRANCE full blood count (FBC) monitoring should be performed at the beginning of each cycle, at day 15 of the first 2 cycles, and as clinically indicated. The dose of IBRANCE may need to be modified depending on the results of the FBC tests1.

Cycle 1

Adapted from IBRANCE®Summary of Product Characteristics1

Cycle 2

Adapted from IBRANCE®Summary of Product Characteristics1

Cycle 3 and beyond

Adapted from IBRANCE®Summary of Product Characteristics1

IBRANCE Dosing Guide

Detailed instructions on dose modifications and CBC monitoring can be found in the IBRANCE Dosing Guide, which contains a user-friendly, cycle per cycle, algorithm for the management of haematologic toxicities based on the recommendations given in  the IBRANCE Summary of Product Characteristics

Grading according to CTCAE 4.0. 
* As per IBRANCE dosing guidelines.1
Applies to all haematologic AEs except lymphopenia (unless associated with clinical events, e.g. opportunistic infections)1
ANC: Grade 1: ANC <LLN - 1.5 x 109 cells/L. Grade 2: ANC 1 - <1.5 x 109 cells/ L. Grade 3: ANC 0.5 - <1 x 109 cells/L. Grade 4: ANC < 0.5 x 109 cells/L1
§
Proactively monitor FBC1

ANC, absolute neutrophil count; CBC, complete blood count; CTCAE, Common terminology criteria for Adverse Events; LLN, lower limit of normal.

Reference:

  1. IBRANCE® Summary of Product Characteristics.

PP-IBR-GBR-2125. December 2019

Neutropenia

In clinical studies and clinical practice, most cases of Grade ≥3 neutropenia occurred during the first two cycles of treatment2,3.

Cumulative incidence of Grade 3/4 neutropenia2*

Adapted from Verma S, et al. Oncologist. 2016;21:1165-75.2

Neutropenia (any grade) was the most frequently reported AE for IBRANCE in combination with endocrine therapy:

  • 81.8% in PALOMA-2 (IBRANCE + letrozole arm)4
  • 84.1% in PALOMA-3 (IBRANCE + fulvestrant arm)5

Across the Phase III IBRANCE clinical trial programme:1

Due to its mechanism of action, IBRANCE-induced neutropenia differs from that seen with chemotherapy2,6,7. Whilst IBRANCE suppresses the bone marrow by inducing cell cycle arrest, chemotherapy causes cellular death, including bone marrow cells6,7. The 3:1 IBRANCE dosing schedule provides a 1-week recovery period that allows arrested bone marrow cells to resume their function, while tumour cell growth remains suppressed by the concomitant ET partner1,7.

*In a population of pre-/peri- and post-menopausal women with HR+/HER2- locally advanced breast cancer with relapse or progression on or after ET in the adjuvant setting, randomised to receive lBRANCE + fulvestrant or placebo + fulvestrant. Data from all randomly assigned patients who received at least one dose of IBRANCE plus fulvestrant2.

AE, adverse event; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive

References:

  1. IBRANCE® Summary of Product Characteristics
  2. Verma S, et al. Oncologist. 2016;21:1165-75.
  3. Kish JK, et al. SABCS Annual Meeting, 2017, San Antonio, TX, USA. Poster P6-16-05.
  4. Rugo HS, et al. Breast Cancer Res Treat. 2019;174:719-29.
  5. Turner NC, et al. N Engl J Med 2018;379:1926-36.
  6. Johnson SM, et al. J Clin Invest. 2010;120:2528-2536.
  7. Hu W, et al. Clin Cancer Res. 2015;22(8):2000-2008.

PP-IBR-GBR-2126. December 2019

Non-haematological toxicities

Non-haematologic toxicities can be managed through dose modifications (temporary dose interruptions, cycle delays, and/or reductions)1.

 

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g. hypoxia, cough, dyspneoa). In patients who have new or worsening respiratory symptoms and are suspected to have developed ILD/pneumonitis, interrupt IBRANCE immediately and evaluate the patient. Permanently discontinue IBRANCE in patients with severe ILD or pneumonitis1*.

IBRANCE Dosing Guide

Detailed instructions on dose modifications and CBC monitoring can be found in the IBRANCE Dosing Guide, which contains a user-friendly, cycle per cycle, algorithm for the management of haematologic toxicities based on the recommendations given in  the IBRANCE Summary of Product Characteristics

Reference:

  1. IBRANCE® Summary of Product Characteristics

PP-IBR-GBR-2127. December 2019