LARTRUVO + doxorubicin safety and tolerability

ADVERSE REACTIONS

Adverse reactions occurring in ≥10% (all grades) of patients in the LARTRUVO + doxorubicin arm and at a higher incidence than in the doxorubicin alone arm (between arm difference of ≥5% for all grades or ≥2% for Grades 3 and 4)

*Abdominal pain includes: abdominal pain, lower abdominal pain, and upper abdominal pain.
Fatigue includes: asthenia and fatigue.
Musculoskeletal pain includes: arthralgia, back pain, bone pain, flank pain, groin pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, muscle spasms, neck pain, and pain in extremity.

The most common (≥20%) adverse reactions of LARTRUVO + doxorubicin were nausea, fatigue, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, and headache.

LABORATORY ABNORMALITIES

Laboratory abnormalities worsening from baseline in >10% (all grades) of patients in the LARTRUVO + doxorubicin arm and occurring at a higher incidence than in the doxorubicin arm (between arm difference ≥5% for all grades and ≥2% for Grades 3 and 4)

*The incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement: LARTRUVO + doxorubicin arm (range 60 to 63 patients) and doxorubicin arm (range 39 to 62 patients).

aPTT=activated partial thromboplastin time.

Febrile neutropenia: 13% for the LARTRUVO + doxorubicin-treated patients vs 12% for the doxorubicin-treated patients.

Discontinuation

Adverse reactions resulting in permanent discontinuation of LARTRUVO occurred in 8% (5/64) of patients.

The most common adverse reaction leading to LARTRUVO discontinuation was infusion-related reaction (3%).

Dose reductions of LARTRUVO for adverse reactions occurred in 25% (16/64) of patients; the most common adverse reaction leading to dose reduction was Grade 3 or 4 neutropenia (20%).

Dose delays of LARTRUVO for adverse reactions occurred in 52% (33/64) of patients; the most common adverse reactions resulting in dose delays were neutropenia (33%), thrombocytopenia (8%), and anemia (5%).
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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