To make sure you continue to receive this e-newsletter, please add info@iononline.com to your address book.

specialty-spotlight-hero
Important Safety Information
     
Neurotoxicity: Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and
Grade 4 neurologic adverse reactions in 6% and 0.6% of patients, respectively.
Dear Healthcare Provider:

Cancer treatment is moving to more patient-focused options.3 This shift includes a growing interest in TRK fusion proteins as potential oncogenic drivers.4 Despite this interest, there hasn’t been an approved therapy—until now.

VITRAKVI is indicated for the treatment of adult and pediatric patients with solid tumors that:

 
have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation,
are metastatic or where surgical resection is likely to result in severe morbidity, and
have no satisfactory alternative treatments or that have progressed following treatment.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory trials.
 
VITRAKVI EFFICACY RESULTS
Response rates across multiple tumor types (as assessed by a blinded IRC,* N=55)1a
The major efficacy outcome measures were ORR and DOR,* as determined by a blinded IRC according to RECIST* v1.1.1
Study design: 55 adult and pediatric patients with unresectable or metastatic solid tumors with an NTRK* gene fusion were included for the pooled efficacy analysis across LOXO-TRK-14001, SCOUT, and NAVIGATE. All patients were required to have progressed following systemic therapy for their disease, if available, or would have required surgery with significant morbidity for locally advanced disease.1
* CNS, central nervous system; CR, complete response; DOR, duration of response; FDA, US Food and Drug Administration; IFS, infantile fibrosarcoma; IRC, independent review committee; NTRK, neurotrophic receptor tyrosine kinase; ORR, overall response rate; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; TRK, tropomyosin receptor kinase.
a Primary CNS* tumors were not included in the primary efficacy analysis.
b Includes 1 pediatric patient with unresectable IFS* who underwent resection following partial response and who remained disease-free at data cut-off.1
c Plus sign denotes ongoing response.
d Blinded IRC-assessed data.
Response rates in various tumor types (as assessed by a blinded IRC, N=55)1
Efficacy Results by Tumor Type for Patients With Solid Tumors
Harboring NTRK Gene Fusions1
Plus sign denotes ongoing response
NA, not applicable due to small numbers or lack of response; NE, not evaluable; PD, progressive disease; SD, stable disease.
e Observed values at data cutoff, not a range.
 
SAFETY FOR VITRAKVI
The safety of VITRAKVI was evaluated in 176 patients, irrespective of NTRK gene fusion status, in 1 of 3 clinical trials
Adverse Reactions Occurring in ≥10% of Patients Treated With VITRAKVI 1
f National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03.
g One Grade 4 adverse reaction of pyrexia.
Explore the PI  
View the Press Release  
Indication
VITRAKVI is indicated for the treatment of adult and pediatric patients with solid tumors that:
have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation,
are metastatic or where surgical resection is likely to result in severe morbidity, and
have no satisfactory alternative treatments or that have progressed following treatment.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Important Safety Information
Neurotoxicity: Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and 0.6% of patients, respectively. The majority (65%) of neurological adverse reactions occurred within the first three months of treatment (range 1 day to 2.2 years). Grade 3 neurologic adverse reactions included delirium (2%), dysarthria (1%), dizziness (1%), gait disturbance (1%), and paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a single patient. Neurologic adverse reactions leading to dose modification included dizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%), and tremor (1%).
Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dose when resumed.
Hepatotoxicity: Among the 176 patients who received VITRAKVI, increased transaminases of any grade occurred in 45%, including Grade 3 increased AST or ALT in 6% of patients. One patient (0.6%) experienced Grade 4 increased ALT. The median time to onset of increased AST was 2 months (range: 1 month to 2.6 years). The median time to onset of increased ALT was 2 months (range: 1 month to 1.1 years). Increased AST and ALT leading to dose modifications occurred in 4% and 6% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 2% of patients.
Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.
Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily.
Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.
Most Common Adverse Reactions (≥20%): The most common adverse reactions (≥20%) were: increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%).
Drug Interactions: Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.
Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.
For important risk and use information about VITRAKVI, please see the full Prescribing Information.
You are encouraged to report side effects or quality complaints of products to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088. For Bayer products you can report these directly to Bayer by clicking here.
References: 1. VITRAKVI [package insert]. Stamford, CT: Loxo Oncology, Inc.; November 2018. 2. Loxo Oncology receives breakthrough therapy designation from U.S. Food and Drug Administration for LOXO-101 [news release]. Stamford, CT: Loxo Oncology, Inc.; July 13, 2016. https://ir.loxooncology.com/press-releases/loxo-oncology-receives-breakthrough-therapy-designation-from-u.s.-food-and-drug-administration-for-loxo-101. Accessed May 10, 2018. 3. Vaishnavi A, Le AT, Doebele RC. Cancer Discov . 2015;5‌(1):25‌-34. 4. Amatu A, Sartore-Bianchi A, Siena S. ESMO Open. 2016;‌1(2):‌e000023. 5. Data on file, Stamford, CT: Loxo Oncology, Inc.; 2018.
     

Salesforce MC
This email was sent by: AmerisourceBergen
1300 Morris Dr, Chesterbrook, PA, 19087 US


Privacy Policy

Update Profile      Manage Subscriptions        Unsubscribe