For:
METex14 mNSCLC
Important Safety Information:


Interstitial Lung Disease (ILD)/Pneumonitis.
ILD/pneumonitis, which can be fatal, occurred in patients treated with TABRECTA™ (capmatinib) tablets. ILD/pneumonitis occurred in 4.5% of patients trea...

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Indication
TABRECTA™ (capmatinib) tablets is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Safety Profile

Adverse Reactions

TABRECTA: tolerability and safety profile

Common adverse reactions across all cohorts in GEOMETRY mono-11

 

TABRECTA (N=334)

COMMON ADVERSE REACTIONS

ALL GRADES (%)

GRADE 3 (%)

GRADE 4 (%)

General disorders and administration-site conditions

Peripheral edemaa

52

9

-

Fatigueb

32

8

-

Noncardiac chest painc

15

2.1

-

Back pain

14

0.9

-

Pyrexiad

14

0.6

-

Weight decreased

10

0.6

-

Gastrointestinal disorders

 

Nausea

44

2.7

-

Vomiting

28

2.4

-

Constipation

18

0.9

-

Diarrhea

18

0.3

-

Respiratory, thoracic, and mediastinal disorders

 

Dyspnea

24

7

0.6

Cough

16

0.6

-

Metabolism and nutrition disorders

 

Decreased appetite

21

0.9

-

 

aPeripheral edema includes peripheral swelling, peripheral edema, and fluid overload.

bFatigue includes fatigue and asthenia.

cNoncardiac chest pain includes chest discomfort, musculoskeletal chest pain, noncardiac chest pain, and chest pain.

dPyrexia includes pyrexia and body temperature increased.

 

The majority of patients who reported adverse reactions (ARs) remained on TABRECTA™ (capmatinib) tablets.1

  • Dose reductions due to ARs occurred in 102 patients (31%), and dose interruptions due to ARs occurred in 163 patients (49%)2

  • 54 patients (16%) treated with TABRECTA discontinued therapy due to ARs1,2

    • Most common ARs leading to discontinuation were peripheral edema (1.8%), pneumonitis (1.8%), fatigue (1.5%), alanine aminotransferase increased (0.9%), aspartate aminotransferase increased (0.9%), nausea (0.9%), vomiting (0.9%), blood bilirubin increased (0.6%), blood creatinine increased (0.6%), general physical health deterioration (0.6%), interstitial lung disease (0.6%), organizing pneumonia (0.6%), and pneumonia (0.6%). A fatal AR occurred in 1 patient (0.3%) due to pneumonitis

Clinically relevant ARs occurring in <10% of patients treated with TABRECTA included pruritus (allergic and generalized), ILD/pneumonitis, cellulitis, acute kidney injury (including renal failure), urticaria, and acute pancreatitis.1

 

Select laboratory abnormalities (≥20%) worsening from baseline in patients who received TABRECTA in GEOMETRY mono-11

 

TABRECTAa

LABORATORY ABNORMALITIES

Grades 1 to 4 (%)

Grades 3 to 4 (%)

Chemistry

Decreased albumin

68

1.8

Increased creatinine

62

0.3

Increased alanine aminotransferase

37

8

Increased alkaline phosphatase

32

0.3

Increased amylase

31

4.4

Increased gamma-glutamyltransferase

29

7

Increased lipase

26

7

Increased aspartate aminotransferase

25

4.9

Decreased sodium

23

6

Decreased phosphate

23

4.6

Increased potassium

23

3.1

Decreased glucose

21

0.3

Hematology

Decreased lymphocytes

44

14

Decreased hemoglobin

24

2.8

Decreased leukocytes

23

0.9

 

aThe denominator used to calculate the rate varied from 320 to 325 based on the number of patients with a baseline value and at least one post-treatment value.

 

References: 1. Tabrecta [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2020. 2. Data on file. Study CINC280A2201. Novartis Pharmaceuticals Corp; 2019. 

Indication

TABRECTA™ (capmatinib) tablets is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.

 

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.


Important Safety Information

Interstitial Lung Disease (ILD)/Pneumonitis. ILD/pneumonitis, which can be fatal, occurred in patients treated with TABRECTA. ILD/pneumonitis occurred in 4.5% of patients treated with TABRECTA in the GEOMETRY mono-1 study, with 1.8% of patients experiencing grade 3 ILD/pneumonitis and 1 patient experiencing death (0.3%). Eight patients (2.4%) discontinued TABRECTA due to ILD/pneumonitis.

 

Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold TABRECTA in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified.

 

Hepatotoxicity. Hepatotoxicity occurred in patients treated with TABRECTA. Increased alanine aminotransferase (ALT)/aspartate aminotransferase (AST) occurred in 13% of patients treated with TABRECTA in GEOMETRY mono-1. Grade 3 or 4 increased ALT/AST occurred in 6% of patients. Three patients (0.9%) discontinued TABRECTA due to increased ALT/AST.

 

Monitor liver function tests (including ALT, AST, and total bilirubin) prior to the start of TABRECTA, every 2 weeks during the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop increased transaminases or bilirubin. Based on the severity of the adverse reaction, withhold, reduce dose, or permanently discontinue TABRECTA.

 

Risk of Photosensitivity. Based on findings from animal studies, there is a potential risk of photosensitivity reactions with TABRECTA. In GEOMETRY mono-1, it was recommended that patients use precautionary measures against ultraviolet exposure, such as use of sunscreen or protective clothing, during treatment with TABRECTA. Advise patients to limit direct ultraviolet exposure during treatment with TABRECTA.

 

Embryo-Fetal Toxicity. Based on findings from animal studies and its mechanism of action, TABRECTA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TABRECTA and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TABRECTA and for 1 week after the last dose.

 

Most Common Adverse Reactions. The most common adverse reactions (≥20%) were peripheral edema (52%), nausea (44%), fatigue (32%), vomiting (28%), dyspnea (24%), and decreased appetite (21%). The most common grade 3 adverse reactions (≥2%) were peripheral edema (9%), fatigue (8%), dyspnea (7%), nausea (2.7%), vomiting (2.4%), and noncardiac chest pain (2.1%).

 

Clinically Relevant Adverse Reactions. Clinically relevant adverse reactions observed in <10% of patients were pruritus (allergic and generalized), ILD/pneumonitis, cellulitis, acute kidney injury (including renal failure), urticaria, and acute pancreatitis.

 

Laboratory Abnormalities. Select laboratory abnormalities (≥20%) worsening from baseline in patients who received TABRECTA were decreased albumin (68%), increased creatinine (62%), decreased lymphocytes (44%), increased ALT (37%), increased alkaline phosphatase (32%), increased amylase (31%), increased gamma-glutamyltransferase (29%), increased lipase (26%), increased AST (25%), decreased hemoglobin (24%), decreased leukocytes (23%), decreased sodium (23%), decreased phosphate (23%), increased potassium (23%), and decreased glucose (21%).

 

Please see full Prescribing Information for TABRECTA.