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[Dear]
[Hello]
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[Dr. Last Name,]
[First Name,]
[First Name Last Name,]
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[Below is some helpful information around the efficacy and safety data for GAVRETO® (pralsetinib).]
[I wanted to follow up on our last conversation. Below is some helpful information around the efficacy and safety data for GAVRETO® (pralsetinib).]
[I have some helpful information around the efficacy and safety data for GAVRETO® (pralsetinib) I’d like to share with you.]
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GAVRETO is the only once-daily targeted RET therapy indicated for1:
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Adult patients with RET fusion+ mNSCLC as detected by an FDA approved test |
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Patients 12 years+ with advanced or metastatic RET-mutant MTC who require systemic therapy |
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Patients 12 years+ with 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 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 see Important Safety Information below, and
full Prescribing Information.
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| mNSCLC=metastatic non–small cell lung cancer; MTC=medullary thyroid cancer; RAI=radioactive iodine; RET=rearranged during transfection. |
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[email fragments]
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[EFFICACY INFORMATION FOR mNSCLC]
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GAVRETO demonstrated robust and durable response with or without prior therapy in patients with RET+ mNSCLC1
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Efficacy and safety with GAVRETO (400 mg orally once daily) was evaluated in patients with RET fusion+ mNSCLC in the ARROW study, a phase 1/2, nonrandomized, open-label, single-arm, multicohort, multicenter clinical trial. Patients with asymptomatic central nervous system metastases, including patients with stable or decreasing steroid use within 2 weeks prior to study entry, were enrolled.
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The major efficacy outcome measures were ORR and DoR, as assessed by a BICR according to RECIST v1.1.
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| BICR=blinded independent central review; DoR=duration of response; ORR=overall response rate; RECIST=Response Evaluation Criteria in Solid Tumors; RET+=rearranged during transfection positive. |
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58% of patients continued to respond to treatment at 6 months* |
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Median time to first response was 1.9 months (range: 1.4-5.6 months)2 |
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SELECT SAFETY INFORMATION
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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.
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Please see additional Important Safety Information below and full Prescribing Information.
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PREVIOUSLY PLATINUM-TREATED PATIENTS
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80% of patients continued to respond to treatment at 6 months* |
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Median time to first response was 1.8 months (range: 1.3-9.1 months)2 |
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Adverse reactions in RET fusion-positive mNSCLC patients (n=220)1
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Serious adverse reactions occurred in 45% of patients who received GAVRETO. The most frequent serious adverse reactions (in ≥2% of patients) was pneumonia, pneumonitis, sepsis, urinary tract infection, and pyrexia.
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Adverse reactions (≥15%) were fatigue (35%), constipation (35%), musculoskeletal pain (32%), hypertension (28%), diarrhea (24%), cough (23%), pyrexia (20%), edema (20%), pneumonia (17%), and dry mouth (16%).
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Calculated using the proportion of responders with an observed duration of response at least 6 months or greater. |
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CI=confidence interval; CR=complete response; NE=not estimable; PR=partial response. |
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[EFFICACY INFORMATION FOR ADVANCED THYROID CANCER]
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GAVRETO demonstrated robust and durable response in RET+ 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. All patients must have had a non-resectable RET-altered solid tumor or MTC per local assessment of tumor tissue and/or blood. All patients must also have had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.1,3
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The major efficacy outcome measures were ORR and DoR, as assessed by a BICR according to RECIST v1.1.
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| BICR=blinded independent central review; DoR=duration of response; MTC=medullary thyroid cancer; ORR=overall response rate; RECIST=Response Evaluation Criteria in Solid Tumors; RET+=rearranged during transfection positive. |
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Efficacy results in advanced or metastatic RET-mutant MTC1
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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)n |
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SELECT SAFETY INFORMATION
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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.
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Please see additional Important Safety Information below and full Prescribing Information.
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PRIOR CABOZANTINIB AND/OR VANDETANIB
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79% of patients continued to respond to treatment at 6 months* |
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Median time to first response was 3.7 months (range: 1.8-12.9 months)2 |
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Efficacy results in advanced or metastatic RET fusion+ thyroid cancer1
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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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Adverse reactions in RET-altered thyroid cancer patients (n=138)1
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Serious adverse reactions occurred in 39% of patients who received GAVRETO. The most frequent serious adverse reactions (in ≥2% of patients) were pneumonia, pneumonitis, urinary tract infection, pyrexia, fatigue, diarrhea, dizziness, anemia, hyponatremia, and ascites.
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Adverse reactions (≥15%) were musculoskeletal pain (42%), constipation (41%), hypertension (40%), fatigue (38%), diarrhea (34%), edema (29%), cough (27%), headache (24%), rash (24%), dyspnea (22%), pyrexia (22%), peripheral neuropathy (20%), dizziness (19%), abdominal pain (17%), dry mouth (17%), dysgeusia (17%), nausea (17%), stomatitis (17%), and decreased appetite (15%).
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Calculated using the proportion of responders with an observed duration of response at least 6 months or greater. |
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CI=confidence interval; CR=complete response; NE=not estimable; PR=partial response. |
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I would be happy to set up a quick
[pick list]
[
falsecall
truevideo chat
truemeeting
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to answer any questions around the efficacy and safety data for GAVRETO.
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[pick list]
[Sincerely]
[Best]
,
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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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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.
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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 2020.
3. Phase 1/2 study of the highly-selective RET inhibitor, pralsetinib (BLU-667), in patients with thyroid cancer, non-small cell lung cancer, and other advanced solid tumors (ARROW). https://clinicaltrials.gov/ct2/show/NCT03037385. Accessed April 22, 2021.
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