6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

ILD/Pneumonitis [see Warnings and Precautions (5.1)]
Hepatotoxicity [see Warnings and Precautions (5.2)]
Pancreatic Toxicity [see Warnings and Precautions (5.3)]
Hypersensitivity reactions [see Warnings and Precautions (5.4)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Metastatic Non-Small Cell Lung Cancer

The safety of TABRECTA was evaluated in GEOMETRY mono-1 [see Clinical Studies (14)]. Patients received TABRECTA 400 mg orally twice daily until disease progression or unacceptable toxicity (N = 373). Among patients who received TABRECTA, 37% were exposed for at least 6 months and 22% were exposed for at least one year.

Serious adverse reactions occurred in 53% of patients who received TABRECTA. Serious adverse reactions in ≥ 2% of patients included dyspnea (7%), pneumonia (7%), pleural effusion (4.3%), musculoskeletal pain (3.8%), general physical health deterioration (2.9%), ILD/pneumonitis (2.7%), edema (2.4%), and vomiting (2.4%). Fatal adverse reactions occurred in 0.5% of patients who received TABRECTA, including pneumonitis (0.3%) and death, not otherwise specified (0.3%).

Permanent discontinuation of TABRECTA due to an adverse reaction occurred in 17% of patients. The most frequent adverse reactions (≥ 1%) leading to permanent discontinuation of TABRECTA were ILD/pneumonitis (2.4%), edema (2.4%), fatigue (1.3%), and pneumonia (1.1%).

Dose interruptions due to an adverse reaction occurred in 57% of patients who received TABRECTA. Adverse reactions requiring dosage interruption in > 2% of patients who received TABRECTA included edema, increased blood creatinine, nausea, increased lipase, vomiting, increased ALT, dyspnea, pneumonia, fatigue, increased amylase, increased AST, musculoskeletal pain, abdominal pain, and increased blood bilirubin.

Dose reductions due to an adverse reaction occurred in 26% of patients who received TABRECTA. Adverse reactions requiring dosage reductions in > 2% of patients who received TABRECTA included edema, increased ALT and increased blood creatinine.

The most common adverse reactions (≥ 20%) in patients who received TABRECTA were edema, nausea, musculoskeletal pain, fatigue, vomiting, dyspnea, cough, and decreased appetite.

Table 3 summarizes the adverse reactions in GEOMETRY mono-1.

Table 3: Adverse Reactions (≥ 10%) in Patients Who Received TABRECTA in GEOMETRY mono-1
aEdema includes edema peripheral, generalized edema, face edema, edema, localized edema, edema genital, eyelid edema, peripheral swelling, scrotal edema, and penile edema. bMusculoskeletal pain includes arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, pain in jaw, spinal pain. cFatigue includes fatigue and asthenia. dPyrexia includes pyrexia and body temperature increased. eCough includes cough, upper airway cough syndrome, and productive cough. fPneumonia includes pneumonia aspiration, pneumonia, pneumonia influenzal, pneumonia bacterial, lower respiratory tract infection, and lung abscess. gRash includes rash, dermatitis acneiform, rash maculo-papular, eczema, erythema multiforme, rash macular, dermatitis, rash erythematous, rash pustular, dermatitis bullous, and rash vesicular. hDizziness includes dizziness, vertigo, and vertigo positional.
Adverse reactions	TABRECTA (N = 373)
	Grades 1 to 4 (%)	Grades 3 to 4 (%)
General disorders and administration-site conditions
Edemaa	59	13
Musculoskeletal painb	40	4.3
Fatiguec	34	8
Pyrexiad	14	0.8
Weight decreased	11	0.5
Gastrointestinal disorders
Nausea	46	2.4
Vomiting	28	2.4
Constipation	19	0.8
Diarrhea	19	0.5
Respiratory, thoracic, and mediastinal disorders
Dyspnea	25	7
Coughe	21	0.5
Pneumoniaf	13	6
Metabolism and nutrition disorders
Decreased appetite	21	1.1
Skin and subcutaneous tissue disorders
Rashg	13	0.5
Nervous system disorders
Dizzinessh	13	0.5

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

Table 4 summarizes the laboratory abnormalities in GEOMETRY mono-1.

Table 4: Select Laboratory Abnormalities (≥ 20%) Worsening From Baseline in Patients Who Received TABRECTA in GEOMETRY mono-1
aThe denominator used to calculate the rate varied from 359 to 364 based on the number of patients with a baseline value and at least one post-treatment value.
Laboratory abnormalities	TABRECTAa
	Grades 1 to 4 (%)	Grades 3 to 4 (%)
Chemistry
Decreased albumin	72	1.9
Increased creatinine	65	0.5
Increased alanine aminotransferase	39	9
Increased amylase	34	4.7
Increased alkaline phosphatase	32	0.6
Increased gamma-glutamyltransferase	30	6
Increased lipase	29	9
Increased aspartate aminotransferase	28	6
Decreased phosphate	26	4.4
Increased potassium	25	4.1
Decreased sodium	24	6
Decreased glucose	23	0.3
Hematology
Decreased lymphocytes	45	14
Decreased leukocytes	25	1.7
Decreased hemoglobin	24	2.8

Other Clinical Trials Experience

The following adverse reactions have been reported following administration of TABRECTA: hypersensitivity and thrombocytopenia.