GAVRETO was generally well tolerated in patients with RET+ advanced thyroid cancer1

RET+=rearranged during transfection positive.

Safety of GAVRETO was evaluated in 138 patients with RET-altered thyroid cancer1


of patients permanently discontinued GAVRETO due to any adverse reaction1


discontinued due to adverse reactions considered treatment-related by the trial investigator33

Adverse reactions resulting in permanent discontinuation which occurred in >1 patient included fatigue, pneumonia, and anemia.

Dose modifications and interruptions in RET-altered thyroid cancer1

Dose reductions due to an adverse reaction occurred in 44% of patients treated with GAVRETO

Adverse reactions requiring dosage reductions in ≥2% of patients included neutropenia, anemia, hypertension, increased blood creatine phosphokinase, decreased lymphocyte count, pneumonitis, fatigue, and thrombocytopenia.

Dosage interruptions due to an adverse reaction occurred in 67% of patients treated with GAVRETO

Adverse reactions requiring dosage interruption in ≥2% of patients included neutropenia, hypertension, diarrhea, fatigue, pneumonitis, anemia, increased blood creatine phosphokinase, pneumonia, urinary tract infection, musculoskeletal pain, vomiting, pyrexia, increased AST, dyspnea, hypocalcemia, cough, thrombocytopenia, abdominal pain, increased blood creatinine, dizziness, headache, decreased lymphocyte count, stomatitis, and syncope.

Adverse reactions (≥15%) in RET-altered thyroid cancer patients who received GAVRETO in ARROW

Adverse Reactions GAVRETO (N=138)
Grades 1-4 (%) Grades 3-4 (%)
Musculoskeletal pain* 42 0.7##
Constipation 41 0.7##
Diarrhea 34 5##
Abdominal pain 17 0.7##
Dry Mouth 17 0
Stomatitis§ 17 0.7##
Nausea 17 0.7##
Hypertension 40 21##
Fatigue|| 38 6##
Edema 29 0
Pyrexia 22 2.2##
Nervous system
Headache# 24 0
Peripheral neuropathy** 20 0
Dizziness†† 19 0.7##
Dysgeusia‡‡ 17 0
Cough§§ 27 1.4##
Dyspnea|||| 22 2.2##
Skin and subcutaneous
Rash¶¶ 24 0
Metabolism and nutrition
Decreased appetite 15 0

*Musculoskeletal pain includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, non-cardiac chest pain, pain in extremity, spinal pain.
Diarrhea includes colitis, diarrhea.
Abdominal pain includes abdominal discomfort, abdominal pain, abdominal pain upper, abdominal tenderness, epigastric discomfort.
§Stomatitis includes mucosal inflammation, stomatitis, tongue ulceration.
||Fatigue includes asthenia, fatigue.
Edema includes eyelid edema, face edema, edema, edema peripheral, periorbital edema.
#Headache includes headache, migraine.
**Peripheral neuropathy includes dysaesthesia, hyperaesthesia, hypoaesthesia, neuralgia, neuropathy peripheral, paraesthesia, peripheral sensory neuropathy, polyneuropathy.
††Dizziness includes dizziness, dizziness postural, vertigo.
‡‡Dysgeusia includes ageusia, dysgeusia.
§§Cough includes cough, productive cough, upper-airway cough syndrome.
||||Dyspnea includes dyspnea, dyspnea exertional.
¶¶Rash includes dermatitis, dermatitis acneiform, eczema, palmar-plantar, erythrodysaesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pustular.
##Only includes a Grade 3 adverse reaction.

Clinically relevant adverse reactions in <15% of patients who received GAVRETO included increased tumor lysis syndrome and creatine phosphokinase.

Select laboratory abnormalities (≥20%) worsening from baseline in patients who received GAVRETO in ARROW

GAVRETO showed Grades 3-4 AST/ALT elevations of 4.3% and 3.6%

Laboratory Abnormality*** GAVRETO (N=138)
Grades 1-4 (%) Grades 3-4 (%)
Decreased calcium (corrected) 70 9
Increased aspartate aminotransferase (AST) 69 4.3
Increased alanine aminotransferase (ALT) 43 3.6
Increased creatinine 41 0
Decreased albumin 41 1.5
Decreased sodium 28 2.2
Decreased phosphate 28 8
Decreased magnesium 27 0.7
Increased potassium 26 1.4
Increased bilirubin 24 1.4
Increased alkaline phosphatase 22 1.4
Decreased lymphocytes 67 27
Decreased hemoglobin 63 13
Decreased neutrophils 59 16
Decreased platelets 31 2.9

***Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available, which ranged from 135 to 138 patients.

Other clinically relevant laboratory abnormalities in patients who received GAVRETO included increased phosphate (40%).