Patients with advanced soft tissue sarcoma (STS) determined to start strong

Hypothetical patient case study.

Claire
52 years old, mother of 1
ECOG PS 0

  • Patient for whom an anthracycline-containing regimen is appropriate
  • Metastases in the lung and other locations
  • STS diagnosis was confirmed in a biopsy
  • No prior chemotherapy

Not amenable to curative treatment

ECOG PS=Eastern Cooperative Oncology Group performance status.

Hypothetical patient case study

Significantly extended median overall survival (OS)

LARTRUVO + doxorubicin vs doxorubicin alone

There were 39 (59%) deaths among patients taking LARTRUVO + doxorubicin compared to 52 (78%) deaths among patients taking doxorubicin alone.

CI=confidence interval; HR=hazard ratio.

More than doubled objective response rate (ORR)

LARTRUVO + doxorubicin vs doxorubicin alone

ORR=complete response (CR) + partial response (PR).

LARTRUVO + doxorubicin: CR=4.5%, PR=13.6%; doxorubicin alone: CR=1.5%, PR=6%.

ORR was based on independent review and assessed according to RECIST criteria v1.1.

ORR does not include stable disease.

Nearly doubled median progression-free survival (PFS)1

LARTRUVO + doxorubicin vs doxorubicin alone

LARTRUVO + doxorubicin led to 37 (56%) total events compared to 34 (51%) events with doxorubicin alone.

PFS based on independent review.

A head-to-head trial

A randomized, phase 2 trial of LARTRUVO + doxorubicin

All patients were permitted to receive dexrazoxane prior to doxorubicin in Cycles 5 to 8.

The efficacy outcome measures were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

ECOG PS=Eastern Cooperative Oncology Group performance status; IV=intravenous; PDGFR-α=platelet-derived growth factor receptor alpha.

*Excluded patients with an ECOG performance status >2, left ventricular ejection fraction <50%; or unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction within 6 months.

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

52% (n=34) of patients in the LARTRUVO + doxorubicin arm and 45% (n=30) of patients in the doxorubicin only arm received treatment as LARTRUVO monotherapy.2

Patients had a tumor specimen available for assessment of PDGFR-α expression by an investigational use assay.

SELECT IMPORTANT SAFETY INFORMATION FOR LARTRUVO

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.

Multiple STS histological subtypes were included in the study3

NOS=not otherwise specified.

*Includes 8% dedifferentiated, 4% myxoid, 3% well-differentiated, 1.5% pleomorphic, and 1% liposarcoma NOS.

Includes 3% extraskeletal myxoid chondrosarcoma, 2% malignant peripheral nerve sheath tumor, 2% myxofibrosarcoma, 2% malignant solitary fibrous tumor, 2% endometrial stromal sarcoma, 1.5% chondrosarcoma, 1.5% epithelioid sarcoma, 1.5% fibrosarcoma, 1.5% low-grade fibromyxoid sarcoma, and 5% other histologies with one patient each.

LARTRUVO is approved under accelerated approval

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