LARTRUVO Dosing and Administra­tion

Treat until disease progression or unacceptable toxicity

21-day cycle
Schedule
  • In study 1, patients in the LARTRUVO + doxorubicin arm who discontinued doxorubicin* were able to continue LARTRUVO monotherapy until disease progression or unacceptable toxicity
  • Do not administer LARTRUVO as an IV push or bolus
  • Refer to doxorubicin prescribing information for dosing and dose modifications

IV=intravenous.

*Discontinuation due to either unacceptable doxorubicin-related toxicity or upon completion of 8 cycles.

Flexible dosing options

LARTRUVO injections (10 mg/mL)

A retrospective analysis reviewed 2,285 patients with STS, calculated the 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

Vial selection guide

The table below can help identify the most appropriate vial size for your patients.*

*Depending on the weight-based dose, the full amount in the vials may not be used.

Infusion-related reactions (IRR)

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. IRR 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 IRRs.

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.

LARTRUVO dose modifications

Infusion-related reactions
  • Permanently discontinue LARTRUVO for Grade 3 or 4 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

Fully human monoclonal antibody developed to disrupt the signal

LARTRUVO disrupts PDGFR-α pathway signaling and can inhibit tumor growth.

As demonstrated in nonclinical studies, LARTRUVO binds PDGFR‑α, preventing receptor activation. LARTRUVO exhibits in vitro and in vivo anti-tumor activity against selected sarcoma cell lines and disrupts the PDGFR-α signaling pathway in in vivo tumor implant models.

PDGFR-α=platelet-derived growth factor receptor alpha.

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

Indication and Important Safety Information
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 additional information about LARTRUVO.

OR HCP ISI 19OCT2016