Phase 3
Completed N=1,436
A Study of Pertuzumab in Combination With Trastuzumab (Herceptin) and a Taxane in First-Line Treatment in Participants With Human Epidermal Growth Factor 2 (HER2)-Positive Advanced Breast Cancer
Source: ClinicalTrials.gov NCT01572038 ↗Enrolled (actual)
1,436
Serious AEs
37.3%
Results posted
Sep 2020
Primary outcomePrimary: Overview of the Number of Participants With at Least One Treatment-Emergent Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) — 1419; 879; 535; 31 Participants
◆ Published Evidence
Highly cited
117citations · ~17 / year
Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).
Summary
This multicenter, open-label, single-arm, Phase IIIb study will evaluate the safety and tolerability of pertuzumab in combination with trastuzumab (Herceptin) and a taxane (docetaxel, paclitaxel or nab-paclitaxel) in first-line treatment in participants with metastatic or locally recurrent HER2-positive breast cancer. Participants will receive pertuzumab intravenously (IV) and trastuzumab (Herceptin) IV plus a taxane in cycles of 3 weeks each until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurs first.
Linked Publications
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Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overview of the Number of Participants With at Least One Treatment-Emergent Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) |
1419; 879; 535; 31; 1037; 946 | — |
| PRIMARY Number of Participants Who Died Over the Course of the Study by Reported Cause of Death (Adverse Events Leading to Death by System Organ Class and Preferred Term) |
658; 581; 42; 35; 11; 1 | — |
| PRIMARY Number of Participants Who Died Within 6 Months of Starting Study Treatment by Reported Cause of Death (Adverse Events Leading to Death by System Organ Class and Preferred Term) |
38; 18; 1; 19; 6; 1 | — |
| PRIMARY Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events, Occurring in ≥1% of Participants by System Organ Class and Preferred Term |
676; 172; 31; 163; 4; 2 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events of Any Grade That Were Related to Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥10% of Participants by System Organ Class |
1037; 629; 491; 462; 252; 207 | — |
| PRIMARY Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events That Were Related to Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥0.5% of Participants by Preferred Term |
286; 59; 28; 28; 19; 15 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events Leading to Discontinuation of Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥0.2% of Participants by Preferred Term |
140; 37; 10; 7; 7; 4 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events Leading to Dose Interruption of Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥0.5% of Participants by Preferred Term |
334; 51; 21; 17; 14; 13 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events to Monitor of Any Grade, Occurring in ≥5% of Participants by Category |
1320; 1096; 668; 618; 478; 439 | — |
| PRIMARY Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events to Monitor, Occurring in ≥0.5% of Participants by Category and Preferred Term |
535; 279; 145; 90; 38; 18 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events of Special Interest by Category and Preferred Term |
91; 90; 75; 8; 7; 1 | — |
| PRIMARY Subgroup Analysis by Region of Enrollment: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab |
385; 74; 9; 37; 16; 14 | — |
| PRIMARY Subgroup Analysis by Age (≤65 vs. >65 Years): Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), TEAEs Leading to Death, Grade ≥3 TEAEs, Any-Grade and Grade ≥3 TEAEs Related to Pertuzumab, and TEAEs to Monitor |
415; 120; 17; 14; 688; 191 | — |
| PRIMARY Subgroup Analysis by Taxane Chemotherapy: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), TEAEs Leading to Death, Grade ≥3 TEAEs, Any-Grade and Grade ≥3 TEAEs Related to Pertuzumab, and TEAEs to Monitor |
300; 210; 22; 14; 16; 1 | — |
| PRIMARY Subgroup Analysis by ECOG Performance Status at Baseline: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab |
502; 33; 837; 41; 273; 13 | — |
| PRIMARY Subgroup Analysis by Visceral Disease at Baseline: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab |
353; 182; 610; 269; 197; 89 | — |
| PRIMARY Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab |
283; 252; 493; 386; 169; 117 | — |
| PRIMARY Subgroup Analysis by Hormone Receptor Status at Baseline: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab |
353; 179; 3; 573; 303; 3 | — |
| PRIMARY Subgroup Analysis by Previous Trastuzumab Therapy: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab |
135; 400; 238; 641; 77; 209 | — |
| PRIMARY Number of Participants With a Congestive Heart Failure Event |
478 | — |
| PRIMARY Time to Onset of the First Episode of Congestive Heart Failure |
NA | — |
| PRIMARY Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Values Over the Course of the Study |
64.6; -1.1; -1.5; -2.1; -1.9; -2.2 | — |
| PRIMARY Number of Participants by Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Categories Over the Course of the Study |
1190; 2; 5; 114; 1110; 0 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities in Hematology and Coagulation Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to NCI-CTC v4.0 |
844; 232; 169; 45; 27; 27 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities in Hematology and Coagulation Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to Normal Range Criteria |
1020; 3; 261; 16; 1; 5 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities in Biochemistry Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to NCI-CTC v4.0 |
610; 425; 26; 19; 25; 75 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities in Biochemistry Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to Normal Range Criteria |
717; 5; 402; 2; 69; 8 | — |
| SECONDARY Progression-Free Survival, as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) |
20.67 | — |
| SECONDARY Subgroup Analysis by Region of Enrollment: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
19.38; 23.79; 25.17; 22.37; 22.83; NA | — |
| SECONDARY Subgroup Analysis by Age (≤65 vs. >65 Years): Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
21.98; 14.72 | — |
| SECONDARY Subgroup Analysis by ECOG Performance Status at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
21.49; 12.88 | — |
| SECONDARY Subgroup Analysis by Taxane Chemotherapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
19.38; 23.23; 19.22 | — |
| SECONDARY Subgroup Analysis by Visceral Disease at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
18.23; 27.24 | — |
| SECONDARY Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
19.12; 23.49 | — |
| SECONDARY Subgroup Analysis by Hormone Receptor Status at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
20.60; 20.73; 32.13 | — |
| SECONDARY Subgroup Analysis by Previous Trastuzumab Therapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
15.38; 23.39 | — |
| SECONDARY Overall Survival |
65.31 | — |
| SECONDARY Subgroup Analysis by Region of Enrollment: Overall Survival |
66.56; 63.57; 55.56; NA; 53.22; NA | — |
| SECONDARY Subgroup Analysis by Age (≤65 vs. >65 Years): Overall Survival |
70.01; 50.10 | — |
| SECONDARY Subgroup Analysis by ECOG Performance Status at Baseline: Overall Survival |
67.25; 31.15 | — |
| SECONDARY Subgroup Analysis by Taxane Chemotherapy: Overall Survival |
66.53; 64.03; 70.87 | — |
| SECONDARY Subgroup Analysis by Visceral Disease at Baseline: Overall Survival |
57.10; 81.08 | — |
| SECONDARY Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Overall Survival |
57.10; 79.80 | — |
| SECONDARY Subgroup Analysis by Hormone Receptor Status at Baseline: Overall Survival |
66.66; 60.19; NA | — |
| SECONDARY Subgroup Analysis by Previous Trastuzumab Therapy: Overall Survival |
54.08; 73.50 | — |
| SECONDARY Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1 |
79.5 | — |
| SECONDARY Percentage of Participants by Best Overall Response as Assessed by the Investigator Using RECIST v1.1 |
14.6; 64.9; 15.3; 4.2; 1.1 | — |
| SECONDARY Subgroup Analysis by Age (≤65 vs. >65 Years): Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1 |
81.7; 70.0 | — |
| SECONDARY Subgroup Analysis by Taxane Chemotherapy: Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1 |
78.4; 82.1; 77.4 | — |
| SECONDARY Clinical Benefit Rate (CR or PR, or SD for at Least 6 Months) Based on Best Overall Response as Assessed by the Investigator Using RECIST v.1.1 |
86.2 | — |
| SECONDARY Duration of Response as Assessed by the Investigator Using RECIST v1.1 |
20.01 | — |
| SECONDARY Time to Response for Participants With Best Overall Response of Complete Response or Partial Response, as Assessed by the Investigator Using RECIST v1.1 |
2.464 | — |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy - Breast Cancer (FACT-B) Questionnaire Total Score Over the Course of the Study |
99.87; 0.40; -1.93; 0.87; 3.03; 3.33 | — |
| SECONDARY Change From Baseline in FACT-B Questionnaire Physical Well-Being Subscale Score Over the Course of the Study |
20.98; -1.13; -1.61; -0.31; 0.51; 0.51 | — |
| SECONDARY Change From Baseline in FACT-B Questionnaire Social Well-Being Subscale Score Over the Course of the Study |
22.24; -0.41; -1.09; -1.02; -1.19; -1.28 | — |
| SECONDARY Change From Baseline in FACT-B Questionnaire Emotional Well-Being Subscale Score Over the Course of the Study |
15.08; 1.69; 1.53; 1.64; 2.02; 1.98 | — |
| SECONDARY Change From Baseline in FACT-B Questionnaire Functional Well-Being Subscale Score Over the Course of the Study |
16.65; -0.47; -0.79; -0.11; 0.46; 0.78 | — |
| SECONDARY Change From Baseline in FACT-B Questionnaire Breast Cancer Subscale Score Over the Course of the Study |
24.98; 0.48; -0.11; 0.52; 0.89; 1.16 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically confirmed adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection
- HER2-positive breast cancer
- Eastern cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- LVEF of at least 50 percent (%)
Exclusion Criteria
- Previous systemic non-hormonal anti-cancer therapy for metastatic or locally recurrent disease
- Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence less than or equal to (</=) 6 months
- Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except for trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting
- Disease progression while receiving trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting
- History of persistent Grade 2 or higher (National Cancer Institute Common Toxicity Criteria [NCI-CTC], Version 4.0) hematological toxicity resulting from previous adjuvant or neoadjuvant therapy
- Central nervous system (CNS) metastases
- Current peripheral neuropathy of Grade 3 or greater (NCI-CTC, version 4.0)
- History of other malignancy within the last 5 years prior to first study drug administration, except for carcinoma in situ of the cervix or basal cell carcinoma
- Inadequate bone marrow, liver or renal function
- Uncontrolled hypertension
- Hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection
Data sourced from ClinicalTrials.gov (NCT01572038) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.