GAVRETO was generally well tolerated in RET+ advanced thyroid cancer1

The safety of GAVRETO was evaluated as a single agent at 400 mg orally once daily in 438 patients, including RET fusion+ mNSCLC (n=220) and RET-altered thyroid cancer (n=138), in ARROW.

  • The most common adverse reactions (≥25%) were constipation, hypertension, fatigue, musculoskeletal pain and diarrhea.
  • The most common Grade 3-4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium (corrected), decreased sodium, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), decreased platelets, and increased alkaline phosphatase.
  • In 34 patients with RET-altered solid tumors, no large mean increase in QTc (>20 ms) was detected in the study.

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

9% of patients permanently discontinued GAVRETO due to any adverse reaction;
3.6% discontinued due to adverse reactions considered treatment-related by the trial investigator1,2

Dose modifications and interruptions in RET-altered thyroid cancer1

44% Dose reductions due to adverse reactions in GAVRETO-treated patients

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

67% Dosage interruptions due to an adverse reaction in GAVRETO-treated patients

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
Musculoskeletal pain* 42 0.7##
Gastrointestinal
Constipation 41 0.7##
Diarrhea 34 5##
Abdominal pain 17 0.7##
Dry Mouth 17 0
Stomatitis§ 17 0.7##
Nausea 17 0.7##
Vascular
Hypertension 40 21##
General
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
Respiratory
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

Laboratory Abnormality* GAVRETO N=138
Grades 1-4 (%) Grades 3-4 (%)
Chemistry
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
Hematology
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%).