Medicinal Products

AZD9291 80 mg

Generic drug of the therapeutic class: Oncology and Hematology
active ingredients: AZD9291
laboratory: Astrazeneca

Coated tablet
bottle of 30
All forms

Indication

AZD9291 is indicated for the treatment of adult patients not eligible for an ongoing clinical trial with locally advanced or metastatic non-small cell lung cancer patients with EGFRm + and T790M mutations who progressed during or after treatment. by an EGF receptor tyrosine kinase inhibitor, and platinum-based chemotherapy or intolerance thereof.

Dosage AZD9291 80 mg film-coated tablet vial of 30

AZD9291 is indicated for the treatment of adult patients not eligible for an ongoing clinical trial with locally advanced or metastatic non-small cell lung cancer patients with EGFRm + and T790M mutations who progressed during or after treatment. by an EGF receptor tyrosine kinase inhibitor, and platinum-based chemotherapy or intolerance thereof.

Against indications

Hypersensitivity to the active substance or to any of the excipients listed under Composition .

Interstitial pneumonitis.

Breastfeeding.

Azd9291 side effects

Tolerance Profile Summary

More than 900 patients with predominantly non-small cell lung cancer NSCLC mutated and T790M positive, were exposed to AZD9291 in clinical trials. The dosage received by these patients was 20 to 240 mg once daily continuously.

Of these, 411 patients were treated with AZD9291 at a continuous dose of 80 mg daily in two single arm studies (AURA extension and AURA 2). And the tolerance data described below relate to this population. Comparative analyzes of safety data from randomized clinical trials are not yet available.

Tabulated list of adverse effects

Table 8 presents the incidence of commonly reported adverse reactions in patients who received AZD9291 therapy. The majority of adverse events were Grade 1 or 2. The most commonly reported adverse events were diarrhea (38%) and skin rash (38%). The incidence of grade 3 or 4 adverse events in both clinical studies was 17% and 0.7%, respectively. The occurrence of an adverse event was responsible for a reduction in the initial dose in 1.9% of patients and a discontinuation of treatment in 3.9% of patients.

Most of the diarrhea was mild. The median time of onset was 17 days with an average duration of 64 days. 38% of patients received anti-diarrheal treatment (eg loperamide). No dehydration or renal failure secondary to diarrhea has been described.

Skin rashes or acnes were usually mild in intensity and non-acneiform. The median time of onset was 17 days with an average duration of 77.5 days. 36% of patients received treatment with topical corticosteroids and emollients.

The following side effects have been identified in clinical studies in patients who received AZD9291 as a treatment for NSCLC. In these studies, patients with a history of interstitial lung disease, drug-induced pneumonitis, radiation pneumonitis requiring corticosteroid treatment or evidence of clinically active interstitial lung disease, and significant clinical abnormalities in rhythm or conduction were excluded. as assessed by a resting ECG (QTC> 470ms).

Adverse reactions are classified according to their frequency and organ system class. Frequency categories are defined according to the following conventions: Very common (≥1 / 10), Common (≥1 / 100 to <1/10), Uncommon (≥1 / 1000 to <1/100), Rare ( ≥1 / 10, 000 to <1/1000), Very rare (<1 / 10, 000), Unknown (can not be estimated based on available data).

The data in Table 8 are cumulative data from the AURA extension (phase II) and AURA2 studies; only events that occurred in patients who received at least one dose of AZD9291 are summarized below.

Table 8 - Adverse Reactions Reported in Studies AURA a

Body Systems

Class (MedDRA)

MedDRA terms

Overall frequency (All grades CTC b ) / according to the CIOMS convention

Frequency of grades 3 and 4

(according to

CTC classification)

Gastrointestinal disorders

intestinal

diarrhea

Very common (37.7%) e

0.7%

stomatitis

Frequent (9.5%) e

0%

Skin disorders and

subcutaneous tissue

Rash c

Very frequent (38.2%) e

0.5%

Dryness of the skin

Very frequent

(26, 0%) e

0%

paronychia

Very common (15.6%)

0%

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease

Frequent (2.2%)

0.5% of cases reported in patients treated with AZD9291 were fatal

0.7%

investigations

(the results are based on the results of the

tests presented as a CTC classification change)

Decrease of platelets

Very common (48.5%)

0.7%

Decreased leucocytes f

Very common (62.9%)

1%

Decrease

neutrophils f

Very common (28.9%)

2.8%

The data described above are cumulative from the AURA extension (phase II) and AURA 2 studies; only events occurring in patients who received at least one dose of AZD9291 are summarized.

b the National Cancer Institute classification (NCI CTCAE) version 4

c Includes cases reported as adverse event group rash: rash, generalized rash, macular rash, maculopapular rash, maculo-vesicular rash, morbilliform rash, vesicular rash, follicular rash, pustular acne, pustular rash, folliculitis, eyelid folliculitis, acne, acne-like dermatitis and drug-induced rash

d Includes cases reported under the grouped terms of: dry skin, skin fissure, xerosis, eczema

e Includes cases reported under the grouped terms: interstitial lung disease, pulmonary disorders, pneumonia, diffuse alveolar damage, pulmonary fibrosis, alveolitis, idiopathic pulmonary fibrosis, acute interstitial pneumonitis, pulmonary toxicity

f represents the incidence of laboratory results and not adverse events reported

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals should report any suspected adverse reactions using the adverse reaction reporting form available in the Therapeutic Use and Information Collection Protocol (see Annex D of the PUT).

Special populations

The elderly

Of the patients treated in the two single arm studies (AURA extension and AURA 2), 32.4% were aged 65 and over, 13.1% were 75 years of age and older. Compared with younger subjects (<65 years), those aged 65 years or older had more adverse effects leading to dose modifications of AZD9291 (discontinuation of treatment or dose reduction) (17, 6% versus 10.7%). The types of adverse events were similar regardless of age. Elderly patients had more grade ≥3 adverse events compared to younger patients (23.5% versus 16.1%). No difference in efficacy was observed between these subjects and the younger subjects.

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