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| Dear Healthcare Provider, |
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GAVRETO™ (pralsetinib) is the only once-daily targeted RET therapy for adults with RET fusion+ mNSCLC and for patients 12 years+ with advanced or metastatic RET-mutant MTC who require systemic
therapy, or advanced or metastatic RET fusion+ thyroid cancer who require systemic therapy and are RAI refractory.
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These indications are approved under accelerated approval. Please see Important Safety Information below and click here to see the full Prescribing Information for GAVRETO.
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GAVRETO demonstrated robust and durable
response with or without prior therapy in advanced thyroid cancers1
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Efficacy and safety with GAVRETO (400 mg orally once
daily) was evaluated in patients with advanced or metastatic RET-mutant+ MTC and advanced or metastatic RET fusion+ thyroid cancer in the ARROW study, a phase 1/2, nonrandomized, open-label, single-arm, multicohort, multicenter clinical trial.
The major efficacy outcome measures were overall response rate (ORR) and duration of response (DoR), as assessed by a blinded independent central review (BICR) according to RECIST v1.1.
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Efficacy results with GAVRETO in advanced or metastatic RET-mutant MTC1,2
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CABOZANTINIB AND VANDETANIB-NAÏVE
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> 84% of patients continued to respond to treatment at 6 months*
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> Median time to first response was 3.7 months (range: 1.7-11.1 months)2
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PRIOR CABOZANTINIB AND/OR VANDETANIB1
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| > 79% of patients continued to respond to treatment at 6 months* |
| > Median time to first response was 3.7 months (range: 1.8-12.9 months)2 |
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Efficacy results with GAVRETO in advanced or metastatic RET-fusion+ thyroid cancer1,2
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> 100% of patients continued to respond to treatment at 6 months*
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> Median time to first response was 1.9 months (range: 1.8-5.5 months)2
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SELECT SAFETY INFORMATION
Interstitial Lung Disease (ILD)/Pneumonitis occurred in 10% of
patients who received GAVRETO, including 2.7% with Grade 3/4,
and 0.5% with fatal reactions. Monitor for pulmonary symptoms
indicative of ILD/pneumonitis. Withhold GAVRETO and promptly
investigate for ILD in any patient who presents with acute or
worsening of respiratory symptoms (e.g., dyspnea, cough, and
fever). Withhold, reduce dose or permanently discontinue
GAVRETO based on severity of confirmed ILD.
Please see additional Select Safety Information below
and click here to see the full Prescribing Information.
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| * |
Calculated using the proportion of responders with an observed duration of
response at least 6 months or greater.
CI=confidence interval; CR=complete
response; MTC=medullary thyroid cancer, NE=not estimable; NSCLC=non–small cell lung cancer; NR=not reached; PR=partial response; RAI=radioactive iodine; RECIST=Response Evaluation Criteria in Solid Tumors; RET=rearranged during transfection.
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GAVRETO was generally well tolerated1
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.
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SELECT SAFETY INFORMATION
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| GAVRETO has warnings and precautions of: |
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• ILD/Pneumonitis
• Hypertension
• Hepatotoxicity
• Hemorrhagic Events
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• Tumor Lysis Syndrome
• Risk of Impaired Wound Healing
• Embryo-Fetal Toxicity
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Safety of GAVRETO was evaluated in 138 patients
with RET-altered thyroid cancer in ARROW
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9% of patients permanently discontinued GAVRETO due to any adverse reaction;
3.6% discontinued due to adverse reactions considered treatment related
by the trial investigator.1,2
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Adverse reactions resulting in permanent discontinuation which occurred in
>1 patient included fatigue, pneumonia, and anemia.
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Hypertension occurred in 29% of patients, including Grade 3 hypertension in 14% of patients. Overall, 7% had their dose interrupted and 3.2% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate GAVRETO in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating GAVRETO. Monitor blood pressure after 1 week, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue GAVRETO based on the severity.
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Hepatotoxicity: Serious hepatic adverse reactions occurred in 2.1% of patients treated with GAVRETO. Increased aspartate aminotransferase (AST) occurred in 69% of patients, including Grade 3/4 in 5% and increased alanine aminotransferase (ALT) occurred in 46% of patients, including Grade 3/4 in 6%. The median time to first onset for increased AST was 15 days (range: 5 days to 1.5 years) and increased ALT was 22 days (range: 7 days to 1.7 years). Monitor AST and ALT prior to initiating GAVRETO, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue GAVRETO based on severity.
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Grade ≥ 3 hemorrhagic events occurred in 2.5% of patients treated with GAVRETO including one patient with a fatal hemorrhagic event. Permanently discontinue GAVRETO in patients with severe or life-threatening hemorrhage.
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Tumor Lysis Syndrome (TLS): Cases of TLS have been reported in patients with medullary thyroid carcinoma receiving GAVRETO. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated.
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Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, GAVRETO has the potential to adversely affect wound healing. Withhold GAVRETO for at least 5 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of GAVRETO after resolution of wound healing complications has not been established.
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Based on findings from animal studies and its mechanism of action, GAVRETO 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 non-hormonal contraception during treatment with GAVRETO and for 2 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with GAVRETO and for 1 week after the final dose. Advise women not to breastfeed during treatment with GAVRETO and for 1 week after the final dose.
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Common adverse reactions (≥25%) were constipation, hypertension, fatigue, musculoskeletal pain and diarrhea. Common Grade 3/4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium (corrected), decreased sodium, increased AST, increased ALT, decreased platelets and increased alkaline phosphatase.
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Avoid coadministration of GAVRETO with strong CYP3A inhibitors or combined P-gp and strong CYP3A inhibitors. If coadministration cannot be avoided, reduce the GAVRETO dose. Avoid coadministration of GAVRETO with strong CYP3A inducers. If coadministration cannot be avoided, increase the GAVRETO dose.
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GAVRETO is indicated for the treatment of:
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Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test
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Adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy
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Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)
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These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
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Please click here to see the full Prescribing Information for GAVRETO.
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References: 1. GAVRETO™ (pralsetinib). Prescribing Information. Blueprint Medicines Corporation; Cambridge, MA. December 2020. 2. Data on file. Blueprint Medicines Corporation; Cambridge, MA. December 2020.
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Information for Vermont Prescribers
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