General Information

Lartruvo (olaratumab) is a platelet-derived growth factor receptor alpha (PDGFR-α) blocking antibody.

Lartruvo is specifically indicated for use 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.

Lartruvo is supplied as an injection for intravenous administration. The recommended dose of Lartruvo is 15 mg/kg administered as an intravenous 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. Refer to doxorubicin prescribing information for dosing, and dose modifications.

Clinical Results

FDA Approval

Lartruvo was approved under accelerated approval. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial. The efficacy of Lartruvo was demonstrated in Trial 1, an open-label, randomized, active-controlled study. Eligible patients were required to have soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy, a histologic type of sarcoma for which an anthracycline-containing regimen was appropriate but had not been administered, ECOG PS of 0-2, and tumor specimen available for assessment of PDGFR-α expression by an investigational use assay. One hundred and thirty-three (133) patients were randomized (1:1) to receive Lartruvo in combination with doxorubicin or doxorubicin as a single agent. PDGFR-α expression (positive versus negative), number of previous lines of treatment (0 versus 1 or more), histological tumor type (leiomyosarcoma versus synovial sarcoma versus all others), and ECOG PS (0 or 1 versus 2) were used to allocate patients in the randomization. Lartruvo was administered at 15 mg/kg as an intravenous infusion on Days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity. All patients received doxorubicin 75 mg/m2 as an intravenous infusion on Day 1 of each 21-day cycle for a maximum of eight cycles and were permitted to receive dexrazoxane prior to doxorubicin in Cycles 5 to 8. Patients randomized to receive doxorubicin as a single agent were offered Lartruvo at the time of disease progression. The efficacy outcome measures were overall survival (OS), and progression-free survival (PFS) and objective response rate (ORR). Median OS was improved by 11.8 months in patients randomized to receive Lartruvo plus doxorubicin compared to patients randomized to doxorubicin alone, and was statistically significant. Median OS was 26.5 months on the Lartruvo-doxorubicin arm compared to 14.7 months on the doxorubicin-only arm. The study met its prespecified protocol-defined endpoint for PFS. Patients treated on the Lartruvo and doxorubicin arm achieved 8.2 months of median PFS compared to 4.4 months on the doxorubicin-only arm, based on independent review. The number of events at the time of analysis was 37 (56%) on the Lartruvo-doxorubicin arm and 34 (51%) on the doxorubicin-only arm. The number of deaths at the time of analysis was 39 (59%) on the Lartruvo-doxorubicin arm and 52 (78%) on the doxorubicin-only arm. Objective response rate (ORR), based on independent review and defined as complete response (CR) plus partial response (PR), was also assessed with an ORR of 18.2 percent on the Lartruvo-doxorubicin arm and 7.5 percent on the doxorubicin-only arm.

Side Effects

Adverse effects associated with the use of Lartruvo may include, but are not limited to, the following:

nausea

fatigue

musculoskeletal pain

mucositis

alopecia

vomiting

diarrhea

decreased appetite

abdominal pain

neuropathy

headache

The most common (≥20%) laboratory abnormalities were lymphopenia, neutropenia, thrombocytopenia, hyperglycemia, elevated aPTT, hypokalemia, and hypophosphatemia

The use of Lartruvo may result in infusion-related reactions and embryo-fetal toxicity

Mechanism of Action

Lartruvo (olaratumab) is a platelet-derived growth factor receptor alpha (PDGFR-α) blocking antibody. PDGFR-α is a receptor tyrosine kinase expressed on cells of mesenchymal origin. Signaling through this receptor plays a role in cell growth, chemotaxis, and mesenchymal stem cell differentiation. The receptor has also been detected on some tumor and stromal cells, including sarcomas, where signaling can contribute to cancer cell proliferation, metastasis, and maintenance of the tumor microenvironment. The interaction between olaratumab and PDGFR-α prevents binding of the receptor by the PDGF-AA and -BB ligands as well as PDGF-AA, -BB, and -CC-induced receptor activation and downstream PDGFR-α pathway signaling.