Drug Trials Snapshot: RUBRACA
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 RUBRACA Prescribing Information for complete information.
RUBRACA (rucaparib)
roo-brah’-kah
Clovis Oncology, Inc.
Approval date: December 19, 2016
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
RUBRACA is a drug used to treat women with advanced ovarian cancer who:
- have certain BRCA gene mutation (either inherited or acquired), and
- have received previous treatment with 2 or more chemotherapy medicines for their cancer.
How is this drug used?
Two tablets (total of 600 mg) are taken two times a day with or without food.
What are the benefits of this drug?
Fifty-four percent of 106 women who were treated with RUBRACA experienced complete or partial shrinkage of their tumors lasting on an average 9.2 months.
More trials are ongoing to confirm the clinical benefit of RUBRACA.
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes efficacy results for the clinical trials based on the efficacy population. Objective response rate (ORR) and duration of response (DOR) were assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and were supported by independent radiology review.
Table 2. Overall Response and Duration of Response in Patients with BRCA-mutant Ovarian Cancer Who Received Two or More Chemotherapies in Trial 1 and Trial 2
| Investigator-assessed N=106 |
|
|---|---|
| Objective Response Rate (95% CI) | 54% (44, 64) |
| Complete Response | 9% |
| Partial Response | 45% |
| Median DOR in months (95% CI) | 9.2 (6.6 ,11.6) |
RUBRACA Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
The disease occurs only in women, therefore only race and age differences were analyzed.
- Race: The majority of patients in the clinical trials were White. Differences in response to RUBRACA among races could not be determined.
- Age: The number of participants above 65 years of age was limited; therefore, differences in response between patients above and below 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 efficacy results of Objective Response Rate (ORR) and median Duration of Response (DOR) in months by age and racial subgroup.
Table 3. Subgroup Analysis of Objective Response Rate (ORR) and Median Duration of Response (DOR) As Assessed by the Investigator
|
|
ORR n % (95% CI) |
Median DOR (95% CI) |
|---|---|---|
|
Age Group |
||
|
65 years="" (n=""> |
35 (51.5) (39, 63.8) |
8.9 (5.5,11.7) |
|
≥65 years (n=38) |
22 (57.9) (40.8,73.7) |
9.7 (6.6, NR) |
|
Race |
||
|
White (n=83) |
46 (55.4) (44.1, 66.3) |
9.7 (5.7, 12.9) |
|
Non-White (n=13) |
6 (46.2) (19.2, 74.9) |
7.6 (4.4, NR) |
|
Unknown (10) |
5 (50) (18.7, 81.3) |
NR (9.2, NR) |
NR = Not Reached
Adapted from FDA Statistical review
What are the possible side effects?
The most common side effects of RUBRACA are nausea, tiredness, vomiting, low red cell count in the blood (anemia), stomach-area pain, unusual taste sensation, constipation, decreased appetite, diarrhea, low platelet count in the blood, and shortness of breath.
RUBRACA may cause serious side effects including a bone marrow disorder (myelodysplastic syndrome) and leukemia and may harm an unborn baby.
What are the possible side effects (results of trials used to assess safety)?
The tables below summarize adverse reactions and electrolyte abnormalities in the combined clinical trials (safety population).
Table 4. Adverse Reactions reported in ≥ 20% of Patients with Ovarian Cancer Treated with RUBRACA 600mg Twice Daily
| Adverse Reaction | All Ovarian Cancer Patients (N = 377) % |
|
|---|---|---|
| Grades a 1-4 | Grades 3-4 | |
| Gastrointestinal Disorders | ||
| Nausea | 77 | 5 |
| Vomiting | 46 | 4 |
| Constipation | 40 | 2 |
| Diarrhea | 34 | 2 |
| Abdominal Pain | 32 | 3 |
| General Disorders | ||
| Asthenia/Fatigue | 77 | 11 |
| Blood and Lymphatic System Disorders | ||
| Anemia | 44 | 25 |
| Thrombocytopenia | 21 | 5 |
| Nervous System Disorders | ||
| Dysgeusia | 39 | 0.3 |
| Metabolism and Nutrition Disorders | ||
| Decreased appetite | 39 | 3 |
| Respiratory, Thoracic, and Mediastinal Disorders | ||
| Dyspnea | 21 | 0.5 |
aNational Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03)
RUBRACA Prescribing Information
Table 5. Laboratory Abnormalities Reported in ≥ 35% of Patients with Ovarian Cancer Treated with RUBRACA 600 mg Twice Daily
| Laboratory Parameter | All Patients with Ovarian Cancer (N = 377) % |
|
|---|---|---|
| Grade 1-4 a | Grade 3-4 | |
| Clinical Chemistry | ||
| Increase in creatinine | 92 | 1 |
| Increase in ALTb | 74 | 13 |
| Increase in ASTb | 73 | 5 |
| Increase in cholesterol | 40 | 2 |
| Hematologic | ||
| Decrease in hemoglobin | 67 | 23 |
| Decrease in lymphocytes | 45 | 7 |
| Decrease in platelets | 39 | 6 |
| Decrease in absolute neutrophil count | 35 | 10 |
aAt least one worsening shift in CTCAE grade and by maximum shift from baseline.
bIncrease in ALT/AST led to treatment discontinuation in 0.3% of patients (1/377).
RUBRACA Prescribing Information
Were there any differences in side effects among sex, race and age?
Were there any differences in side effects among sex, race, and age?
The disease occurs only in women, therefore only race and age differences were analyzed.
- Race: The majority patients in the clinical trials were White. Differences in side effects among races could not be determined.
- Age: The occurrence of side effect was similar between patients below and above 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The table below summarizes treatment emergent adverse events (TEAEs) during the clinical trials by race and age subgroup.
Table 6. Subgroup Analysis of Treatment-Emergent Adverse Events by Race (N=339)*
| RUBRACA | ||
|---|---|---|
| Non-White (N=37) |
White (N=302) |
|
| TEAEa | 37 (100%) | 302 (100%) |
| Serious TEAEa | 13 (35.1) | 83 (27.4%) |
| ≥ Grade 3 TEAEa | 24 (64.9) | 182 (60.1%) |
*38 (10%) of patients had race missing
aincluded events of disease progression
TEAE=Treatment Emergent Adverse Event
FDA Clinical review
Table 7. Subgroup Analysis of Treatment-Emergent Adverse Events by Age (N=377)
| RUBRACA | ||||
|---|---|---|---|---|
| Age 65=""> N = 217 |
Age ≥65 to 75 > N = 119 |
Age ≥75 Years N = 41 |
Age ≥65 Years N = 160 |
|
| TEAEa | 217 (100%) | 119 (100%) | 41 (100%) | 160 (100%) |
| Serious TEAEa | 59 (27.2%) | 36 (30.3%) | 9 (22%) | 45 (28.1%) |
| ≥ Grade 3 TEAEa | 125 (57.6%) | 78 (65.5%) | 26 (63.4%) | 104 (65%) |
aincluded events of disease progression
FDA Clinical review
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The benefit of RUBRACA was evaluated based on evidence from 106 patients with advanced ovarian cancer enrolled in two clinical trials of. These patients form the efficacy population and will be presented in the Figures 1a-3a below.
The safety of RUBRACA (side effects) was evaluated on a population from the same two trials and one additional trial. All of these patients together (total of 377) form the safety population and will be presented in Figures 1b-3b below.
The trials were conducted in the USA, Canada, Australia, Europe, and Israel.
Figures 1a and 1b summarize how many women were in the clinical trials used to evaluate the benefits and side effects of RUBRACA.
Figure 1a. Baseline Demographics by Sex (efficacy population)
Clinical trial data
Figure 1b. Baseline Demographics by Sex (safety population)
Clinical trial data
Figure 2a and Table 2a below summarize the percentage of patients by race in the clinical trials used to evaluate the benefits of RUBRACA.
Figure 2a. Baseline Demographics by Race (efficacy population)
Clinical trial data
Table 1a. Baseline Demographics by Race (efficacy population)
| Race | Number of Patients | Percentage |
|---|---|---|
| White | 83 | 78 |
| Black or African American | 4 | 4 |
| Asian | 7 | 7 |
| Other | 2 | 2 |
| Missing | 10 | 9 |
Clinical trial data
Figure 2b and Table 2b below summarize the percentage of patients by race in the clinical trials used to evaluate the side effects of RUBRACA.
Figure 2b. Baseline Demographics by Race (safety population)
*includes American Indian or Alaska Native, Multiple and Other
Clinical trial data
Table 1b. Baseline Demographics by Race (safety population)
| Race | Number of Patients | Percentage |
|---|---|---|
| White | 302 | 80% |
| Black or African American | 8 | 2% |
| Asian | 22 | 6% |
| American Indian or Alaska Native | 1 | less than % |
| Multiple | 2 | 1% |
| Other | 4 | 1 |
| Missing | 38 | 10% |
Clinical trial data
Figures 3a and 3b below summarize the percentage of patients by age in the clinical trials used to evaluate the benefits and side effects of RUBRACA.
Figure 3a. Baseline Demographics by Age (efficacy population)
Clinical trial data
Figure 3b. Baseline Demographics by Age (safety population)
Clinical trial data
Who participated in the trials?
The table below summarizes demographics of patients in the clinical trials based on the efficacy population.
Table 8. Baseline Demographics of Patients in the Clinical Trials (efficacy population)
| Demographic Parameters | RUBRACA N =106 n (%) |
|---|---|
| Sex | |
| Women | 106 (100) |
| Age | |
| Median (Range) | 59 (33-84) |
| Age Group | |
| 65> | 68 (63) |
| ≥65 years | 38 (37) |
| Race | |
| White | 83 (78%) |
| Asian | 7 (7%) |
| Black of African American | 4 (4) |
| Other | 2 (2) |
| Missing | 10 (9) |
| Region | |
| US | 26 (25) |
| Australia | 4 (4) |
| Europe | 31 (29) |
| Canada | 31 (29) |
| Israel | 14 (13) |
Clinical trial data
The table below summarizes demographics of patients in the clinical trials based on the safety population.
Table 9. Baseline Demographics of Patients in the Clinical Trials (safety population)
| Demographic Parameters | RUBRACA N=377 n (%) |
|---|---|
| Sex | |
| Women | 377 (100) |
| Age | |
| Median (Range) | 62 (31-86) |
| Age Group | |
| 65> | 217 (58) |
| 65-75 years | 119 (32) |
| ≥75 years | 41 (11) |
| Race | |
| White | 302 (80%) |
| Asian | 22 (6%) |
| Black of African American | 8 (2) |
| American Indian or Alaska Native | 1 (> |
| Other | 4 (1) |
| Multiple | 2 (1) |
| Missing | 38 ( 10) |
| Ethnicity | |
| Non-Hispanic or Latino | 317 (84) |
| Hispanic or Latino | 13 (3) |
| Not reported | 43 (11) |
| Missing | 4 (1) |
| Region | |
| US | 142 (38) |
| Europe | 120 (32) |
| Canada | 83 (22) |
| Other | 32 (8) |
Clinical trial data
How were the trials designed?
The benefit and side effects of RUBRACA were evaluated in two clinical trials of patients with advanced ovarian cancer. All patients received RUBRACA twice a day until either the disease worsened or the patients developed an unacceptable side effect.
The benefit of RUBRACA was evaluated by measuring the proportion of patients whose tumor size decreased by at least 30% during treatment and by how long that response lasted.
How were the trials designed?
There were two single-arm, open-label, multicenter clinical trials. Patients in the efficacy population had advanced BRCA-mutant ovarian cancer and had progressed after 2 or more prior chemotherapies. All patients received RUBRACA twice daily as monotherapy until disease progression or unacceptable toxicity.
The efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) assessed by the investigator and supported by independent radiology review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
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.