Established safety profile

 

PALOMA pooled analysis: adverse reactions & laboratory abnormalities
PALOMA pooled analysis: ARs based on pooled dataset from 3 randomised studies (N=872)1
 
established-safety-profile
  • The median duration of IBRANCE® treatment across the pooled dataset at the time of the final overall survival analysis was
    14.8 months.1

Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported.
*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. **Adverse Drug Reaction (ADR) identified post-marketing. ††ILD/pneumonitis includes any reported PTs that are part of the Standardised MedDRA Query Interstitial Lung Disease (narrow). ‡‡Stomatitis includes the following PTs: Aphthous stomatitis, Cheilitis, Glossitis, Glossodynia, Mouth ulceration, Mucosal 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 eruption.

AR = adverse reactions; ALT = alanine aminotransferase; AST = aspartate aminotransferase; ILD = interstitial lung disease; MedDRA = Medical Dictionary for Regulatory Activities; N/A = not applicable; N/n = number of patients.

 

PALOMA pooled analysis: Laboratory abnormalities* observed in pooled dataset from 3 randomised studies (N=872)1

 
  • The median duration of IBRANCE® treatment across the pooled dataset at the time of the final overall survival analysis was
    14.8 months.1

*Note: Laboratory results are graded according to the NCI CTCAE version 4.0 severity grade. Letrozole or fulvestrant.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; N = number of patients; N/A = not applicable; NCI CTCAE = National Cancer Institute Common Toxicity Criteria for adverse events; WBC = white blood cells.

 
Safety profile overview
IBRANCE® has a well-characterised and consistent safety profile2-5

 

In a PALOMA-2 post-hoc exploratory analysis, dose reductions did not appear to affect the efficacy of 1st line IBRANCE® + letrozole at a landmark of 9 months*6

 

This was an intra-arm comparison. When evaluating the data, note this analysis was not powered to make comparisons within treatment arms and patient numbers were small.  

Adapted from Diéras V, et al. 2019.6
Data cut-off date: February 26, 2016.

  • Among patients with all-causality AEs associated with dose reduction in the IBRANCE® + letrozole arm, 67.5% had a dose reduction associated with neutropenia (24.3% of patients in the IBRANCE® + letrozole arm vs 0.5% of patients in the placebo + letrozole arm)
  • 14.4% had a dose reduction associated with decreased neutrophil count (5.2% in the IBRANCE® arm vs 0% in the placebo arm)
  • 3.8% had a dose reduction associated with febrile neutropenia (1.4% in the IBRANCE® arm vs 0% in the placebo arm)

*Patients with PFS time ≤9 months were excluded.
AE = adverse event; AR = adverse reaction; AST = aspartate aminotransferase; LET = letrozole; = number of patients; PFS = progression-free survival.

 
Safety profile across subgroups
IBRANCE® has a well-characterised and consistent safety profile1-4
established-safety-profile
 

AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; ET = endocrine therapy; GI = gastrointestinal; QTc = QT interval corrected for heart rate; TEAE = treatment-emergent adverse event.

References

1. IBRANCE® Summary of Product Characteristics.
2. Finn RS, et al. N Engl J Med. 2016;375(20):1925-1936.
3. Cristofanilli M, et al. Lancet Oncol. 2016;17(4):425-439.
4. Verma S, et al. Oncologist. 2016;21:1165-1175.
5. Dieras V, et al. J Natl Cancer Inst. 2019;111(4):419-430.
6. Dieras V, et al. Oncologist. 19 Jun 2019. Epub ahead of print.
7. Rugo HS, et al. Eur J Cancer. 2018;101:123-133.
8. Turner NC, et al. Ann Oncol. 2018;29(3):669-680.
9. Durairaj C, et al. Anticancer Drugs. 2018;29(3):271-280.

 

PP-IBR-IRL-0373 Date of Preparation January 2020