LARTRUVO Dosing and Administration

Dosing

1-HOUR INFUSION of LARTRUVO

15 mg/kg 60-minute IV infusion LARTRUVO 15 mg/kg 60-minute IV infusion LARTRUVO Administer for up to 8 cycles following LARTRUVO infusion DOXORUBICIN + DAY 1 DAY 8

Schedule

2 days of active treatment per 21-day cycle

LARTRUVO + doxorubicin LARTRUVO 1 8 2 3 4 5 6 7 9 10 11 12 13 14 16 15 17 18 19 20 21
  • The recommended dose of LARTRUVO is 15 mg/kg administered as an intravenous (IV) infusion over 60 minutes on Days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity
  • For the first 8 cycles, LARTRUVO is administered with doxorubicin, which is given on Day 1 of each cycle following the LARTRUVO infusion
  • Do not administer LARTRUVO as an IV push or bolus
  • Refer to doxorubicin prescribing information for dosing and dose modifications

LARTRUVO injections (10 mg/mL)

Flexible dosing options

A retrospective analysis reviewed 2285 patients with STS, calculated the necessary dose needed for each patient, and estimated the average waste associated with dispensing LARTRUVO 500 mg/50 mL vials. The average waste per patient per administration was approximately 234 mg. Using a combination of 190 mg/19 mL and 500 mg/50 mL vials, the average waste per patient per administration was reduced to 29 mg, an 87.6% reduction.1

Infusion-Related Reactions

Infusion-related reactions (IRR) occurred in 70 (14%) of 485 patients who received at least one dose of LARTRUVO across clinical trials. For 68 of these 70 patients (97%), the first occurrence of IRR was in the first or second cycle. Grade ≥3 IRR occurred in 11 (2.3%) of 485 patients, with one (0.2%) fatality. Symptoms of IRR included flushing, shortness of breath, bronchospasm, or fever/chills, and in severe cases symptoms manifested as severe hypotension, anaphylactic shock, or cardiac arrest. Infusion-related reactions required permanent discontinuation in 2.3% of patients and interruption of infusion in 10% of patients. All 59 patients with Grade 1 or 2 IRR resumed LARTRUVO; 12 (20%) of these patients had a Grade 1 or 2 IRR with rechallenge. The incidence of IRR in the overall safety database (N=485) was similar (18% versus 12%) between those who did (56%) and those who did not (44%) receive premedication. Monitor patients during and following LARTRUVO infusion for signs and symptoms of IRR in a setting with available resuscitation equipment. Immediately and permanently discontinue LARTRUVO for Grade 3 or 4 IRR.

Premedication

Premedicate with diphenhydramine (25 mg to 50 mg intravenously) and dexamethasone (10 mg to 20 mg intravenously) prior to LARTRUVO on Day 1 of Cycle 1.

Dosing Modifications

Infusion-Related Reactions
  • Permanently discontinue LARTRUVO for Grade 3 or 4 infusion-related reactions (IRR)
  • Interrupt infusion of LARTRUVO for Grade 1 or 2 IRRs. After resolution, resume LARTRUVO infusion at 50% of the initial infusion rate
Neutropenia
  • For neutropenic fever/infection or Grade 4 neutropenia lasting longer than 1 week, discontinue administration of LARTRUVO until the absolute neutrophil count is 1,000/microliter or greater and then permanently reduce the dose to 12 mg/kg

Reference: 1. Data on file. Lilly USA, LLC. OLA20170210.

INDICATION

LARTRUVO is indicated, in combination with doxorubicin, for the treatment of adult patients with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.

This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

IMPORTANT SAFETY INFORMATION FOR LARTRUVO

Warnings and Precautions
Infusion-Related Reactions
  • Infusion-related reactions (IRR) occurred in 70 (14%) of 485 patients who received at least one dose of LARTRUVO across clinical trials. For 68 of these 70 patients (97%), the first occurrence of IRR was in the first or second cycle. Grade ≥3 IRR occurred in 11 (2.3%) of 485 patients, with one (0.2%) fatality. Symptoms of IRR included flushing, shortness of breath, bronchospasm, or fever/chills, and in severe cases symptoms manifested as severe hypotension, anaphylactic shock, or cardiac arrest. Infusion-related reactions required permanent discontinuation in 2.3% of patients and interruption of infusion in 10% of patients. All 59 patients with Grade 1 or 2 IRR resumed LARTRUVO; 12 (20%) of these patients had a Grade 1 or 2 IRR with rechallenge. The incidence of IRR in the overall safety database (N=485) was similar (18% versus 12%) between those who did (56%) and those who did not (44%) receive premedication. Monitor patients during and following LARTRUVO infusion for signs and symptoms of IRR in a setting with available resuscitation equipment. Immediately and permanently discontinue LARTRUVO for Grade 3 or 4 IRR.
Embryo-Fetal Toxicity
  • Based on animal data and its mechanism of action, LARTRUVO can cause fetal harm when administered to a pregnant woman. Animal knockout models link disruption of platelet-derived growth factor receptor alpha (PDGFR-α) signaling to adverse effects on embryo-fetal development. Administration of an anti-murine PDGFR-α antibody to pregnant mice during organogenesis caused malformations and skeletal variations. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LARTRUVO and for 3 months after the last dose.
Most Common Adverse Reactions/Lab Abnormalities
  • The most commonly reported adverse reactions (all grades; grade 3-4) occurring in ≥20% of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were nausea (73% vs 52%; 2% vs 3%), fatigue (69% vs 69%; 9% vs 3%), musculoskeletal pain (64% vs 25%; 8% vs 2%), mucositis (53% vs 35%; 3% vs 5%), alopecia (52% vs 40%; 0% vs 0%), vomiting (45% vs 19%; 0% vs 0%), diarrhea (34% vs 23%; 3% vs 0%) decreased appetite (31% vs 20%; 2% vs 0%), abdominal pain (23% vs 14%; 3% vs 0%), neuropathy (22% vs 11%; 0% vs 0%), and headache (20% vs 9%; 0% vs 0%).
  • The most common laboratory abnormalities (all grades; grade 3-4) occurring in ≥20% of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were lymphopenia (77% vs 73%; 44% vs 37%), neutropenia (65% vs 63%; 48% vs 38%) and thrombocytopenia (63% vs 44%; 6% vs 11%), hyperglycemia (52% vs 28%; 2% vs 3%), elevated aPTT (33% vs 13%; 5% vs 0%), hypokalemia (21% vs 15%; 8% vs 3%), and hypophosphatemia (21% vs 7%; 5% vs 3%).
Use in Specific Populations
  • Lactation: Because of the potential risk for serious adverse reactions in breastfeeding infants, advise women not to breastfeed during treatment with LARTRUVO and for at least 3 months following the last dose.

Please see full Prescribing Information for LARTRUVO.

OR HCP ISI 19OCT2016

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