About RET+ advanced thyroid cancers

Utilize biomarker testing in advanced thyroid cancers to determine appropriate treatment for your patients

There are several types of thyroid cancer, but most are differentiated thyroid cancers17,18

Thyroid cancers are classified according to the types of cells from which they originate. The cell type can help to determine prognosis, as well as clinical management of the disease.17,18

Thyroid types chart

There are less common types of thyroid cancer, such as lymphomas, sarcomas, and other rare tumors.17

RET+=rearranged during transfection positive.

Biomarkers are known to drive oncogenic growth in certain advanced thyroid cancers3,19-28

Differentiated thyroid cancer (DTC)

ALL PTC

~10%-20%

RET fusions19-21

~2%-3%

NTRK rearrangements22

~1%-3%

ALK fusions23

~45%

BRAF V600E mutations3

PTC (≤18 years of age)

~22%

RET fusions24

~26%

NTRK rearrangements24

~48%

BRAF V600E mutations24

Medullary thyroid cancer (MTC)

~90% of patients with metastatic disease have RET mutations25

SMTC

Medullary thyroid cancer donut SMTC

~50% RET26-28

FMTC*

Medullary thyroid cancer donut FMTC

~100% RET26-28

*Germline as part of MEN2 syndrome.

ALK=anaplastic lymphoma kinase; BRAF=B-Raf proto-oncogene; FMTC=familial medullary thyroid cancer; MEN2=multiple endocrine neoplasia type 2; NTRK=neurotrophic tyrosine receptor kinase; PTC=papillary thyroid cancer; SMTC=sporadic medullary thyroid cancer.

Comprehensive biomarker testing is important in advanced thyroid cancers due to the prevalence of actionable biomarkers19,22,25,29

Testing in DTC

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend genomic testing to identify actionable mutations for structurally persistent locally advanced or metastatic DTC not amenable to radioiodine therapy3

  • Test for RET fusions, ALK fusions, NTRK fusions, BRAF mutations, and TMB3

DNA- or RNA-based comprehensive profiling may be appropriate.30

Testing in MTC

NCCN Guidelines® recommend germline RET testing in all patients with a diagnosis of MTC3

  • ALL patients with MTC should be tested for inherited risk3
  • Genetic RET testing should be recommended in all patients with a new diagnosis of MTC3

DNA-based comprehensive profiling for patients requiring systemic therapy may be appropriate, but FISH and RNA panels are not.30

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. FISH=fluorescence in situ hybridization; NCCN=National Comprehensive Cancer Network®; TMB=tumor mutational burden.

RET alterations can be identified via various testing methodologies, including NGS, PCR, and FISH19

It is important to consider that not every laboratory test can detect RET mutations and/or fusions.

Talk to your pathologist to determine the most appropriate lab for testing your patient for biomarkers

NGS=next-generation sequencing; PCR=polymerase chain reaction.

The treatment landscape for advanced thyroid cancer is evolving

Prior to 2020, multikinase inhibitors were approved for the treatment of certain thyroid cancers, but none were specifically approved for a RET+ biomarker-defined patient population.19 With the approval of RET-directed inhibitors, healthcare providers can utilize strategies to specifically target RET as an actionable biomarker in certain advanced thyroid cancers.1,31

Select patients for treatment based on the presence of a RET gene fusion or mutation. Consider a selectively designed RET inhibitor1

An FDA-approved test for the detection of RET gene fusions and mutations is not currently available.

LEARN MORE

Important Safety Information & Indications

INDICATIONS

GAVRETO® (pralsetinib) is indicated for the treatment of:

  • Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test
  • Adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy
  • 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)

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.

IMPORTANT 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.

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.

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.

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.

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.

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.

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.

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.

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.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please click here to see the full Prescribing Information for GAVRETO.

    • GAVRETO Prescribing Information. Genentech, Inc. February 2022.

      GAVRETO Prescribing Information. Genentech, Inc. February 2022.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed March 18, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed March 18, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Thyroid Carcinoma V.3.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed October 18, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Thyroid Carcinoma V.3.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed October 18, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org.

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