Drug Trials Snapshots: FRUZAQLA
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic 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 healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the FRUZAQLA Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
FRUZAQLA (fruquintinib)
(fru-zahk-la)
Takeda Pharmaceuticals America, Inc.
Approval date: November 8, 2023
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
FRUZAQLA is a drug used for the treatment of adults with colorectal cancer that cannot be removed by surgery or has spread to other parts of the body (metastatic).
It should be used in patients who have been previously treated with chemotherapy and other anticancer agents.
How is this drug used?
FRUZAQLA is a capsule that is taken by mouth once daily for 21 days followed by 7 days off treatment to complete a 28-day treatment cycle.
Who participated in the clinical trials?
FRUZAQLA was approved primarily based on evidence from two clinical trials (FRESCO/NCT02314819, FRESCO-2/NCT04322539) that enrolled 1,107 patients with metastatic colorectal cancer with disease progression after prior treatment. FRESCO was conducted entirely in China. FRESCO-2 was conducted at 152 sites across the United States and in 14 other countries. Both clinical trials were used to assess the efficacy and safety of FRUZAQLA.
How were the trials designed?
The efficacy of FRUZAQLA was primarily evaluated in two clinical trials (FRESCO/NCT02314819, FRESCO-2/NCT04322539) that enrolled a total of 1,107 patients with metastatic colorectal cancer with disease progression after prior treatment.
How were the trials designed?
In both trials, patients were randomly assigned (2:1) to receive either FRUZAQLA plus best supportive care (BSC) or placebo plus BSC. Neither the patients nor the healthcare providers knew which treatment was being given until after the trials were completed. In each 4-week cycle, patients received 5 mg of FRUZAQLA once a day for 21 days (three weeks) and then stopped for 7 days (one week). The treatment continued until the disease progressed, the side effects became too toxic, or the patient decided to discontinue the study. The benefit of FRUZAQLA in comparison to placebo was assessed by the length of time patients lived (overall survival).
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the combined clinical trials used to evaluate the efficacy of FRUZAQLA.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the combined clinical trials used to evaluate the efficacy of FRUZAQLA.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the combined clinical trials used to evaluate the efficacy of FRUZAQLA.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the combined clinical trials used to evaluate the efficacy of FRUZAQLA.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Demographics Table, FRESCO
| Demographics Subgroup | FRUZAQLA N=278 |
Placebo N=138 |
Total N=416 |
|---|---|---|---|
|
Sex, n (%) |
|
|
|
|
Female |
120 (43.2) |
41 (29.7) |
161 (38.7) |
|
Male |
158 (56.8) |
97 (70.3) |
255 (61.3) |
|
Age, years |
|
|
|
|
Median (range) |
55 (23,75) |
57 (24, 74) |
56 (23, 75) |
|
Age group, years, n (%) |
|
|
|
|
<65 |
228 (82.0) |
110 (79.7) |
338 (81.3) |
|
≥65 |
50 (18.0) |
28 (20.3) |
78 (18.7) |
|
Race, n (%) |
|
|
|
|
Asian |
278 (100) |
138 (100) |
416 (100) |
Source: Adapted from FDA Review
Table 2. Demographics Table, FRESCO-2
| Demographic Subgroup | FRUZAQLA N=461 |
Placebo N=230 |
Total N=691 |
|---|---|---|---|
| Sex, n (%) | |||
| Female | 216 (46.9) | 90 (39.1) | 306 (44.3) |
| Male | 245 (53.1) | 140 (60.9) | 385 (55.7) |
| Age, years | |||
| Median (range) | 64 (25, 82) | 64 (30, 86) | 64 (25, 86) |
| Age group, years, n (%) | |||
| <65 | 247 (53.6) | 119 (51.7) | 366 (53.0) |
| ≥65 | 214 (46.4) | 111 (48.3) | 325 (47.0) |
| Race, n (%) | |||
| American Indian or Alaska Native | 0 | 1 (0.4) | 1 (0.1) |
| Asian | 43 (9.3) | 18 (7.8) | 61 (8.8) |
| Black or African American | 13 (2.8) | 7 (3.0) | 20 (2.9) |
| Native Hawaiian or other Pacific Islander | 3 (0.7) | 2 (0.9) | 5 (0.7) |
| White | 367 (79.6) | 192 (83.5) | 559 (80.9) |
| Multiple races | 2 (0.4) | 0 | 2 (0.3) |
| Other/Not reported/Unknown | 33 (7.2) | 10 (4.3) | 43 (6.2) |
| Ethnicity, n (%) | |||
| Hispanic or Latino | 20 (4.3) | 14 (6.1) | 34 (4.9) |
| Not Hispanic or Latino | 405 (87.9) | 202 (87.8) | 607 (87.8) |
| Not reported/Unknown | 36 (7.8) | 14 (6.1) | 50 (7.2) |
| Region, n (%) | |||
| Asia Pacific | 50 (10.8) | 22 (9.6) | 72 (10.4) |
| Europe | 329 (71.4) | 166 (72.2) | 495 (71.6) |
| North America | 82 (17.8) | 42 (18.3) | 124 (17.9) |
Source: Adapted from FDA Review
What are the benefits of this drug?
The benefit of FRUZAQLA was evaluated by measuring the length of time that patients survived. In one of the clinical studies, overall survival for patients taking FRUZAQLA was about 7.4 months compared to 4.8 months for patients taking placebo. In the second study, overall survival for patients taking FRUZAQLA was about 9.3 months compared to 6.6 months for patients taking placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
Efficacy results from the clinical trials are summarized in Table 3. The major efficacy outcome measure was overall survival. The approval for FRUZAQLA was based upon a statistically significant improvement in overall survival.
Table 3. Efficacy Results From FRESCO and FRESCO-2
| Overall Survival | FRESCO | FRESCO-2 | ||
|---|---|---|---|---|
| FRUZAQLA N=278 |
Placebo N=138 |
FRUZAQLA N=461 |
Placebo N=230 |
|
| Number of patients with death, n (%) | 188 (68) | 109 (79) | 317 (69) | 173 (75) |
| Median in months (95% CI) | 9.3 (8.2, 10.5) | 6.6 (5.9, 8.1) | 7.4 (6.7, 8.2) | 4.8 (4.0, 5.8) |
| Hazard ratio (95% CI) | 0.65 (0.51, 0.83) | 0.66 (0.55, 0.80) | ||
Source: Adapted from FRUZAQLA Prescribing Information
Abbreviations: CI, confidence interval
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: FRUZAQLA appears to be similarly effective in males and females.
- Race: FRUZAQLA was similarly effective in White and Asian patients. The number of patients of other races was limited; therefore, differences in how FRUZAQLA worked among races could not be determined.
- Age: FRUZAQLA was similarly effective in patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 4. Overall Deaths in FRESCO and FRESCO-2
| Subgroup | FRESCO | FRESCO-2 | |||||
|---|---|---|---|---|---|---|---|
| FRUZAQLA N=278 n/N |
Placebo N=138 n/N |
Hazard Ratio (95% CI) | FRUZAQLA N=461 n/N |
Placebo N=230 n/N |
Hazard Ratio (95% CI) | ||
| Overall death | 188/278 | 109/138 | 0.65 (0.51, 0.83) | 317/461 | 173/230 | 0.66 (0.55, 0.80) | |
| Sex | |||||||
| Male | 108/158 | 77/97 | 0.52 (0.39, 0.70) | 168/245 | 112/140 | 0.58 (0.46, 0.75) | |
| Female | 80/120 | 32/41 | 0.85 (0.57, 1.29) | 168/245 | 112/140 | 0.58 (0.46, 0.75) | |
| Age, years | |||||||
| <65 | 151/228 | 88/110 | 0.56 (0.43, 0.73) | 171/247 | 89/119 | 0.69 (0.53, 0.90) | |
| ≥65 | 37/ 50 | 21/ 28 | 0.95 (0.55, 1.63) | 146/214 | 84/111 | 0.65 (0.49, 0.85) | |
Source: Adapted from FDA Review
Abbreviations: CI, confidence interval
What are the possible side effects?
FRUZAQLA may cause serious side effects including hypertension, bleeding, infections, gastrointestinal perforation, liver damage, increased protein in the urine, palmar-plantar erythrodysesthesia (rash, redness, pain, swelling or blisters on the palms of the hands or soles of the feet), wound healing complications, arterial clogging, allergies, posterior reversible encephalopathy syndrome (a serious neurological condition that may present as headaches, seizures, confusion, changes in vision, and problems thinking), and harm to an unborn baby.
The most common side effects of FRUZAQLA are hypertension, palmar-plantar erythrodysesthesia, increased protein in the urine, hoarseness, abdominal pain, diarrhea, and tiredness.
What are the possible side effects (results of trials used to assess safety)?
Table 5. Adverse Reactions (≥10%) in Patients Who Received FRUZAQLA and With a Difference Between Arms of ≥5% Compared to Placebo in FRESCO (All Grades)
| Adverse Reaction | FRUZAQLA, N=278 | Placebo, N=137 | ||
|---|---|---|---|---|
| All Grades % |
Grade 3 or 4 % |
All Grades % |
Grade 3 or 4 % |
|
| Vascular | ||||
| Hypertension | 61 | 23 | 17 | 2.2 |
| Hemorrhage | 28 | 1.1 | 14 | 0 |
| Renal | ||||
| Proteinuria | 55 | 4.7 | 30 | 0 |
| Skin and subcutaneous | ||||
| Palmar-plantar erythrodysesthesia (hand-foot skin reactions) | 49 | 11 | 2.9 | 0 |
| Respiratory | ||||
| Dysphonia | 38 | 0 | 1.5 | 0 |
| Throat pain | 10 | 0 | 1.5 | 0 |
| Gastrointestinal | ||||
| Stomatitis | 33 | 0.7 | 2.9 | 0 |
| Abdominal pain | 29 | 4 | 17 | 1.5 |
| Diarrhea | 25 | 3.6 | 5 | 0 |
| General | ||||
| Fatigue | 25 | 2.5 | 13 | 1.5 |
| Metabolism | ||||
| Anorexia | 21 | 1.4 | 9 | 0 |
| Musculoskeletal | ||||
| Musculoskeletal pain | 22 | 2.2 | 6 | 1.5 |
| Back pain | 15 | 1.8 | 7 | 0 |
| Arthralgia | 13 | 0.4 | 2.2 | 0 |
| Endocrine disorders | ||||
| Hypothyroidism | 17 | 0 | 2.2 | 0 |
Source: FRUZAQLA Prescribing Information
Table 6. Adverse Reactions (≥10%) in Patients Who Received FRUZAQLA and With a Difference Between Arms of ≥5% Compared to Placebo in FRESCO-2 (All Grades)
| Adverse Reaction | FRUZAQLA, N=456 | Placebo, N=230 | ||
|---|---|---|---|---|
| All Grades % |
Grade 3 or 4 % |
All Grades % |
Grade 3 or 4 % |
|
| General | ||||
| Fatigue | 53 | 12 | 39 | 4.8 |
| Vascular | ||||
| Hypertension | 38 | 14 | 9 | 0.9 |
| Gastrointestinal | ||||
| Stomatitis | 31 | 2.2 | 7.8 | 0.4 |
| Abdominal pain | 25 | 3.5 | 20 | 3 |
| Diarrhea | 24 | 3.7 | 11 | 0 |
| Endocrine disorders | ||||
| Hypothyroidism | 21 | 0.4 | 0.4 | 0 |
| Skin and subcutaneous | ||||
| Palmar-plantar erythrodysesthesia (hand-foot skin reactions) | 19 | 6 | 2.6 | 0 |
| Renal | ||||
| Proteinuria | 18 | 1.8 | 5 | 0.9 |
| Respiratory | ||||
| Dysphonia | 18 | 0 | 5 | 0 |
| Musculoskeletal | ||||
| Musculoskeletal pain | 16 | 1.1 | 7 | 0 |
| Arthralgia | 11 | 0.9 | 4.3 | 0 |
Source: FRUZAQLA Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: Almost all patients experienced side effects. The occurrence of grade 3 to 4 adverse events was similar in White and Asian participants. Among the few Black or African American participants, grade 3 to 4 adverse events were observed more frequently than in White or Asian participants.
- Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 7. Adverse Reactions in FRUZAQLA by Subgroup
| Subgroup | FRUZAQLA, N=911 | |
|---|---|---|
| All Grades n/Ns (%) |
Grade ≥3 n/Ns (%) |
|
| Age, years | ||
| <65 | 594/603 (98.5) | 378/603 (62.7) |
| ≥65 | 305/308 (99.0) | 200/308 (64.9) |
| Sex | ||
| Male | 499/507 (98.4) | 301/507 (59.4) |
| Female | 400/404 (99.0) | 277/404 (68.6) |
| Race | ||
| White | 426/431 (98.8) | 272/431 (63.1) |
| Asian | 412/419 (98.3) | 262/419 (62.5) |
| Black or African American | 21/21 (100) | 16/21 (76.2) |
| Other | 40/40 (100) | 28/40 (70.0) |
Source: Adapted from FDA Review
Abbreviations: N, number of patients in treatment arm; n, number of patients meeting criteria; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
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.