Drugs

Drug Trials Snapshots: LARTRUVO

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to LARTRUVO Prescribing Information for complete information.

LARTRUVO (olaratumab)
(Lär – troo – vō)
Eli Lilly and Comp.
Approval date: October 19, 2016


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

LARTRUVO is a drug used to treat a type of cancer called soft tissue sarcoma. It is to be used in adult patients together with another anti-cancer drug called doxorubicin when radiation or surgery is not possible.

Soft tissue sarcoma (STS) is a rare type of cancer that begins in the soft tissues of the body, such as muscles, tendons, fat, and blood vessels. There are more than 50 different types of STS.

How is this drug used?

LARTRUVO is given by a health care professional directly into the bloodstream through a needle in the vein. This is known as an intravenous, or IV infusion. LARTRUVO intravenous infusion is given over 60 minutes on Days 1 and 8 of each 21-day treatment cycle.

What are the benefits of this drug?

The patients who received LARTRUVO with doxorubicin lived longer than the patients who received doxorubicin alone. In the clinical trial that led to FDA approval, on average, patients taking LARTRUVO with doxorubicin lived 26.5 months and patients taking doxorubicin 14.7 months.

The length of time tumors did not grow after treatment with LARTRUVO with doxorubicin was on average 8.2 months compared to 4.4 months for patients who received doxorubicin alone.

The percent of patients with an objective response (tumor shrinkage) was 18.2 percent for patients who received LARTRUVO with doxorubicin and 7.5 percent for those who received doxorubicin alone. Given the small number of patients in the trial, there may be no difference in objective response rate between the two groups of patients.

More trials are ongoing to confirm and further assess the clinical benefit of LARTRUVO in different types of soft tissue sarcoma.

What are the benefits of this drug (results of trials used to assess efficacy)?

The table below summarizes efficacy results for the clinical trial based on overall survival, progression free survival and objective response rate.

Table 2. Efficacy Results in Trial 1

 LARTRUVO + Doxorubicin
N=66
Doxorubicin
N=67
Overall Survival
Number of deaths (%)39 (59%)52 (78%)
Median, months (95% CI)26.5 (20.9, 31.7)14.7 (9.2, 17.1)
Hazard Ratio (95% CI)a0.52 (0.34, 0.79)
p-valuep<0.05
Progression-Free Survivalb
Number of events (%)37 (56%)34 (51%)
Median, months (95% CI)8.2 (5.5, 9.8)4.4 (3.1, 7.4)
Hazard Ratio (95% CI)a0.74 (0.46, 1.19)
Objective Response Rate (CR + PR)b
(95% CI)18.2% (9.8, 29.6)7.5% (2.5, 16.6)
CR, n (%)3 (4.5%)1 (1.5%)
PR, n (%)9 (13.6%)4 (6%)

Abbreviations: CI = confidence interval, CR = complete response, PR = partial response
a Stratified Cox model
b Based on independent review.

LATRUVO Prescribing Information

The figure below depicts efficacy results for the clinical trial based on overall survival.

Figure 4: Kaplan-Meier Curves of Overall Survival

Graph depicts overall survival for the clinical trial

LARTRUVO Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: LARTRUVO worked similarly in men and women.
  • Race: The majority of patients in the clinical trial were white. Differences in response to LARTRUVO among races could not be determined.
  • Age: The majority of patients in the clinical trial were younger than 65 years of age. Differences in response to LARTRUVO between patients below and above 65 years of age could not be determined.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The table below summarizes Overall Survival (OS) efficacy results by subgroup.

Table 3. Subgroup Analysis of Overall Survival

 Sample Size (EVTS/N)HR (95% CI)
Overall39/66 : 52/670.52 (0.34, 0.79)
Age group
<=6530/48 : 33/430.54 (0.33, 0.89)
>659/18 : 19/240.48 (0.22, 1.07)
Sex
Men16/26 : 28/330.55 (0.3, 1.02)
Women23/40 : 24/340.53 (0.3, 0.94)
Race
Asian1/2 : 2/20.62 (0.05, 7)
Black Or African American3/6 : 3/50.5 (0.1, 2.49)
White32/55 : 47/600.52 (0.33, 0.81)

EVTS=events, HR=hazard ratio, CI-confidence interval
FDA review

What are the possible side effects?

The most common side effects of LARTRUVO are nausea, fatigue, low levels of white blood cells, pain in muscles and joints, inflammation of the mucous membranes, hair loss, vomiting, diarrhea, decreased appetite, abdominal pain, nerve damage, and headache.

LARTRUVO may cause serious side effects, including infusion reactions and harm to an unborn baby.

What are the possible side effects (results of trials used to assess safety)?

The table below summarizes adverse reactions that occurred in the clinical trial in ≥10% of patients in the LARTRUVO plus doxorubicin arm and at a higher Incidence than in the doxorubicin arm.

Table 4. Adverse Reactions Occurring in ≥10% (All Grades) of Patients in the LARTRUVO plus Doxorubicin Arm and at a Higher Incidence than in the Doxorubicin Arm (Between Arm Difference of ≥5% for All Grades or ≥2% for Grades 3 and 4) (Trial 1)

Adverse ReactionsLARTRUVO plus Doxorubicin
N=64
Doxorubicin
N=65
All Grades
(%)
Grade 3-4
(%)
All Grades
(%)
Grade 3-4
(%)
Gastrointestinal Disorders
Nausea732523
Mucositis533355
Vomiting450190
Diarrhea343230
Abdominal Paina233140
General Disorders and Administrative Site Conditions
Fatigueb699693
Infusion-Related Reactions13330
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal Painc648252
Skin and Subcutaneous Tissue Disorders
Alopecia520400
Metabolic and Nutritional Disorders
Decreased Appetite312200
Nervous System Disorders
Neuropathy220110
Headache20090
Psychiatric Disorder
Anxiety11030
Eye Disorder
Dry Eyes11030

a Abdominal pain includes: abdominal pain, lower abdominal pain, and upper abdominal pain.
b Fatigue includes: asthenia and fatigue.
c 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.

LARTRUVO Prescribing Information

The table below summarizes laboratory abnormalities in the clinical trial.

Table 5. Laboratory Abnormalities Worsening from Baseline in >10% (All Grades) of Patients in the LARTRUVO plus Doxorubicin Arm and Occurring at a Higher Incidence than in the Doxorubicin Arm (Between Arm Difference ≥5% for All Grades or ≥2% for Grades 3 and 4) (Trial 1)

Laboratory AbnormalityLARTRUVO plus DoxorubicinaDoxorubicina
All Grades
(%)
Grades 3-4
(%)
All Grades
(%)
Grades 3-4
(%)
Chemistry
Hyperglycemia522283
Increased aPTTb335130
Hypokalemia218153
Hypophosphatemia21573
Increased Alkaline Phosphatase16070
Hypomagnesemia16080
Hematology
Lymphopenia77447337
Neutropenia65486338
Thrombocytopenia6364411

a The incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement: LARTRUVO plus doxorubicin arm (range 60 to 63 patients) and doxorubicin arm (range 39 to 62 patients).
b aPTT = activated partial thromboplastin time

LARTRUVO Prescribing Information

 

Were there any differences in side effects among sex, race and age?

  • Sex: The risk of side effects was similar in men and women
  • Race: The majority patients in the clinical trial were white. Differences in side effects among races could not be determined.
  • Age: The majority of patients in the clinical trial were younger than 65 years of age. Differences in side effects between patients below and above 65 years of age could not be determined.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Tables below summarize adverse events during the clinical trial by subgroup.

Table 6. Subgroup Analysis of Treatment-Emergent Adverse Events by Age–All Grades

 LARTRUVO + Doxorubicin
N=64
Single-agent Doxorubicin
N=65
<65
N=47
n (%)
≥65
N=17
n (%)
<65
N=41
n (%)
≥65
N=24
n (%)
Any TEAE47 (100)16 (94.1)40 (97.6)24 (100)
Grade 3-4 TEAEs36 (76.6)15 (88.2)27 (65.9)18 (70.0)
Grade 5 TEAEs003 (73.1)6 (25.0)
Any SAE20 (42.6)7 (41.2)15 (36.6)10 (41.7)

TEAE=treatment-emergent adverse event
SAE=serious adverse event

Table 7. Subgroup Analysis of Treatment-Emergent Adverse Events by Sex–All Grades

 LARTRUVO + Doxorubicin
N=64
Single-agent Doxorubicin
N=65
Men
N=26
n (%)
Women
N=38
n (%)
Men
N=32
n (%)
Women
N=33
n (%)
Any TEAE22 (96.2)38 (100)32 (100)32 (97.0)
Grade 3-4 TEAEs19 (73.1)32 (84.2)21 (65.6)24 (72.7)
Grade 5 TEAEs008 (12.5)1 ( 3.0)
Any SAE8 (30.8)19 (50.0)12 (37.5)13 (39.4)

TEAE=treatment-emergent adverse event
SAE=serious adverse event

Table 8. Subgroup Analysis of Treatment-Emergent Adverse Events by Race–All Grades

 LARTRUVO + Doxorubicin
N=64
Single-agent Doxorubicin
N=65
White
N=53
n (%)
Non-White
N=11
n (%)
White
N=59
n (%)
Non-White
N=6
n (%)
Any TEAE52 (98.1)11 (100)58 (98.3)6 (100)
Grade 3-4 TEAEs43 (81.1)8 (72.7)42 (71.2)3 (50.0)
Grade 5 TEAEs008 (13.6)1 (16.7)
Any SAE2 (41.5)5 (45.5)23 (39.0)2 (33.3)

TEAE=treatment-emergent adverse event
SAE=serious adverse event
FDA Review

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved LARTRUVO based primarily on the evidence from one clinical trial of 133 patients with advanced soft tissue sarcoma. The trial was conducted in the USA.

The figure below summarizes how many men and women were in the clinical trial.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trial of the drug LARTRUVO. In total, 59 men (44%) and 74 women (56%) participated in the clinical trial.

Clinical trial data

Figure 2 and Table 1 below summarize the percentage of patients by race enrolled in the clinical trials.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the LARTRUVO clinical trial. In total, 115 Whites (86%), 11 Blacks (8%), 4 Asians (3%), and 3 Other (2%) participated in the clinical trial.

Clinical trial data

Table 1. Demographics of Trial by Race

RaceNumber of PatientsPercentage
White11586
Black or African American118
Asian43
Other32

Clinical trial data

Figure 3 summarizes the percentage of patients by age enrolled in the clinical trial.

Figure 3. Baseline Demographics by Age

Pie chart summarizing how many individuals of certain age groups were enrolled in the LARTRUVO clinical trial.  In total, 91 patients was below 65 years old (68%) and 42 patients were 65 and older (32%).

Clinical trial data

Who participated in the trials?

The table below summarizes demographics of patients in the clinical trial.

Table 9. Baseline Demographics of Patients in the Clinical Trial

Demographic parameterLARTRUVO + Doxorubicin
N=66
n (%)
Doxorubicin
N=67
n (%)
Total
N=133
n (%)
Age
Mean (SD)56.8 (12.5)58.3 (12.5)57.6 (12.5)
Median (min-max)58.5 (22-85)58.0  (29-86)58 (22-86)
Age Group
18-<6548 (73)43 (64)91 (68)
≥6518 (27)24 (35)42(32)
Sex
Men26 (39)33 (49)59(44)
Women40 (61)34 (51)74 (56)
Race
White55 (83)60 (90)115 (86)
Black6 (9)5 (7)11 (8)
Asian2 (3)2 (3)4 (3)
Other3 (5)03 (2)
Country
U.S.66 (100)67 (100)133 (100)

Clinical trial data

How were the trials designed?

The benefit and side effects of LARTRUVO were evaluated in one clinical trial of 133 patients with advanced soft tissue sarcoma. About half of the patients received LARTRUVO together with doxorubicin and half received only doxorubicin. The benefit of LARTRUVO was evaluated by measuring the length of time patients lived after treatment (overall survival), the length of time tumors did not grow after treatment (progression-free survival), and the percentage of patients who experienced shrinkage of their tumors (objective response rate).

How were the trials designed?

The safety and efficacy of LARTRUVO were established in single, open label, randomized, two-arm, active-controlled, multicenter clinical trial. Patients with advanced soft tissue sarcoma (STS) whose disease was not amenable to treatment with surgery or radiation, and who had not received prior anthracycline therapy were randomized to receive LARTRUVO + doxorubicin on day 1 and 8 of each 21-day cycle or doxorubicin alone on day 1 of each 21-day cycle.

Treatment continued for up to eight cycles or until disease progression or unacceptable treatment-related toxicity.

The efficacy outcome measures were overall survival (OS), and progression-free survival (PFS) and objective response rate (ORR) as assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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Page Last Updated: 11/03/2016
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