LARTRUVO + doxorubicin significantly extended overall survival (OS)

Progression-Free Survival (PFS)


LARTRUVO + doxorubicin more than doubled ORR compared to doxorubicin alone: 18.2% (95% CI: 9.8, 29.6) vs 7.5% (95% CI: 2.5, 16.6)

LARTRUVO + DOXORUBICIN: Granted Breakthrough Therapy designation and accelerated FDA approval

A head-to-head, Phase 2 randomized trial

LARTRUVO, in combination with doxorubicin, was studied in a multicenter, randomized, open-label, active-controlled trial in 133 patients (n=66 vs n=67) with STS with a histologic type for which an anthracycline-containing regimen was appropriate but had not been administered and which was not amenable to curative treatment with surgery or radiotherapy.

Patients had a tumor specimen available for assessment of PDGFR-α expression.
*Excluded patients with left ventricular ejection fraction <50%; or unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction.
52% of patients in the LARTRUVO + doxorubicin arm and 45% of patients in the doxorubicin only arm continued treatment with LARTRUVO monotherapy.

All patients received the cardioprotectant 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=Eastern Cooperative Oncology Group.

Multiple STS histological subtypes were included in the study

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, and 1.5% low-grade fibromyxoid sarcoma, and 5% other histologies with one patient each.


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

LARTRUVO + doxorubicin led to 37 (56%) total events compared to 34 (51%) events with 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 assessed according to RECIST criteria v1.1.

References: 1. Tap WD, Jones RL, Van Tine BA, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016;338:488-497. 2. Data on file. Lilly USA, LLC. LAR20161014a. 3. Data on file. Lilly USA, LLC. ONC20160229b.

  • 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.


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.