Phase 3
Completed N=4,804
A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer
Source: ClinicalTrials.gov NCT01358877 ↗Enrolled (actual)
4,804
Serious AEs
31.0%
Results posted
Jan 2018
Primary outcomePrimary: Percentage of Participants With Invasive Disease-Free Survival (IDFS) Event (Excluding Second Primary Non-Breast Cancer [SPNBC]), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings — 7.1; 8.7 percentage of participants — p=0.0446
◆ Published Evidence
Established
26citations · ~13 / year
Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update.
Summary
This randomized, double-blind, placebo-controlled, two-arm study will assess the safety and efficacy of pertuzumab in addition to chemotherapy plus trastuzumab as adjuvant therapy in participants with operable HER2-positive primary breast cancer. This study will be carried out in collaboration with the Breast International Group (BIG).
Linked Publications (5)
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Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update.
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Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab in early HER2-positive breast cancer in the APHINITY trial.
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Six-year absolute invasive disease-free survival benefit of adding adjuvant pertuzumab to trastuzumab and chemotherapy for patients with early HER2-positive breast cancer: A Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY (BIG 4-11) trial.
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Patient-reported function, health-related quality of life, and symptoms in APHINITY: pertuzumab plus trastuzumab and chemotherapy in HER2-positive early breast cancer.
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The benefit of adjuvant pertuzumab and trastuzumab according to estrogen receptor and HER2 expression: a Sub-analysis of the APHINITY trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Invasive Disease-Free Survival (IDFS) Event (Excluding Second Primary Non-Breast Cancer [SPNBC]), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
7.1; 8.7 | 0.0446 sig |
| PRIMARY Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Excluding SPNBC) at 3 Years, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
94.06; 93.24 | — |
| SECONDARY Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Excluding SPNBC) at 6, 8, and 10 Years, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
90.56; 87.76; 88.43; 85.76; 87.17; 83.82 | — |
| SECONDARY Percentage of Participants With IDFS Event (Including SPNBC), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
7.9; 9.6 | 0.0430 sig |
| SECONDARY Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Including SPNBC) at 3 Years, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
93.50; 92.51 | — |
| SECONDARY Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Including SPNBC) at 6, 8, and 10 Years, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
89.31; 86.42; 87.08; 83.82; 85.23; 81.31 | — |
| SECONDARY Percentage of Participants With Disease-Free Survival (DFS) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
8.0; 9.8 | 0.0327 sig |
| SECONDARY Kaplan-Meier Estimate of the Percentage of Participants Who Were DFS Event-Free at 3 Years, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
93.42; 92.29 | — |
| SECONDARY Kaplan-Meier Estimate of the Percentage of Participants Who Were DFS Event-Free at 6, 8, and 10 Years, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
88.99; 86.03; 86.92; 83.19; 85.01; 80.54 | — |
| SECONDARY Percentage of Participants Who Died, First Interim Overall Survival Analysis |
3.3; 3.7 | 0.4673 |
| SECONDARY Percentage of Participants Who Died, Final Overall Survival Analysis |
8.54; 10.27 | 0.0441 sig |
| SECONDARY Kaplan-Meier Estimate of the Percentage of Participants Who Were Alive at 3 Years |
97.65; 97.67 | — |
| SECONDARY Kaplan-Meier Estimate of the Percentage of Participants Who Were Alive at 6, 8, and 10 Years |
94.78; 93.93; 92.74; 91.96; 91.55; 89.79 | — |
| SECONDARY Percentage of Participants With Recurrence-Free Interval (RFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
5.8; 7.2 | 0.0430 sig |
| SECONDARY Kaplan-Meier Estimate of the Percentage of Participants Who Were RFI Event-Free at 3 Years, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
95.18; 94.27 | — |
| SECONDARY Kaplan-Meier Estimate of the Percentage of Participants Who Were RFI Event-Free at 6, 8, and 10 Years, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
92.49; 89.91; 92.11; 88.88; 91.87; 88.10 | — |
| SECONDARY Percentage of Participants With Distant Recurrence-Free Interval (DRFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
5.0; 6.0 | 0.1007 |
| SECONDARY Kaplan-Meier Estimate of the Percentage of Participants Who Were DRFI Event-Free at 3 Years, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
95.70; 95.13 | — |
| SECONDARY Kaplan-Meier Estimate of the Percentage of Participants Who Were DRFI Event-Free at 6, 8, and 10 Years, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
93.37; 91.57; 92.94; 90.69; 92.85; 90.01 | — |
| SECONDARY Percentage of Participants With Primary Cardiac Event, Primary Analysis |
0.7; 0.3; 0.6; 0.2; 0.1; 0.1 | — |
| SECONDARY Percentage of Participants With Primary Cardiac Event, Final Analysis |
0.9; 0.5; 0.8; 0.3; 0.1; 0.2 | — |
| SECONDARY Percentage of Participants With Secondary Cardiac Event, Primary Analysis |
2.7; 2.8 | — |
| SECONDARY Percentage of Participants With Secondary Cardiac Event, Final Analysis |
2.9; 3.0 | — |
| SECONDARY Change From Baseline in LVEF to Worst Post-Baseline Value, Primary Analysis |
65.2; 65.3; -7.5; -7.6 | — |
| SECONDARY Change From Baseline in LVEF to Worst Post-Baseline Value, Final Analysis |
65.2; 65.3; -8.6; -8.6 | — |
| SECONDARY Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score |
72.9; 72.5; -11.2; -10.2; -4.4; -2.9 | — |
| SECONDARY Change From Baseline in EORTC QLQ-C30 Functioning Subscale Scores |
89.6; 89.1; -10.7; -10.6; -4.6; -4.3 | — |
| SECONDARY Change From Baseline in EORTC QLQ-C30 Disease/Treatment-Related Symptoms Subscale Scores |
5.2; 5.1; 22.3; 9.2; 13.2; 3.3 | — |
| SECONDARY Change From Baseline in EORTC QLQ-C30 Financial Difficulties Subscale Scores |
20.3; 22.1; 3.1; 1.7; 2.3; -0.3 | — |
| SECONDARY Change From Baseline in European Organisation for Research and Treatment of Cancer - Breast Cancer Module Quality of Life (EORTC QLQ-BR23) Functional Scale Score |
79.7; 78.9; -12.9; -13.9; -7.6; -7.3 | — |
| SECONDARY Change From Baseline in EORTC QLQ-BR23 Symptom Scale Score |
9.5; 10.2; 21.1; 21.7; 9.2; 8.2 | — |
| SECONDARY Percentage of Participants With Response for European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Domain |
93.8; 92.9; 6.2; 6.9; 0.0; 0.2 | — |
| SECONDARY Percentage of Participants With Response for EQ-5D-3L Questionnaire: Self-Care Domain |
89.7; 90.7; 10.0; 9.1; 0.3; 0.2 | — |
| SECONDARY Percentage of Participants With Response for EQ-5D-3L Questionnaire: Usual Activities Domain |
67.4; 66.1; 30.4; 32.2; 2.2; 1.7 | — |
| SECONDARY Percentage of Participants With Response for EQ-5D-3L Questionnaire: Pain/Discomfort Domain |
49.0; 49.0; 50.0; 49.7; 1.0; 1.3 | — |
| SECONDARY Percentage of Participants With Response for EQ-5D-3L Questionnaire: Anxiety/Depression Domain |
47.1; 44.7; 49.4; 50.1; 3.5; 5.2 | — |
| SECONDARY Trough Serum Concentration (Cmin) of Pertuzumab |
68.0; 88.1; 95.5 | — |
| SECONDARY Cmin of Trastuzumab |
32.1; 34.1; 65.0; 68.4; 72.9; 71.0 | — |
| SECONDARY Peak Serum Concentration (Cmax) of Pertuzumab |
237; 222; 206 | — |
| SECONDARY Cmax of Trastuzumab |
180; 190; 219; 225; 187; 234 | — |
Eligibility Criteria
Inclusion Criteria
- Non-metastatic operable primary invasive HER2-positive carcinoma of the breast that is histologically confirmed, and adequately excised
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to ( /=) 55 percent (%) measured by echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan
- Confirmed HER2 positive status
- Completion of all necessary baseline laboratory and radiologic investigations prior to randomization
- Women of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception (as defined by the protocol) by the participant and/or partner for the duration of the study treatment and for at least 7 months after the last dose of study drug
Exclusion Criteria
- History of any prior (ipsi- and/or contralateral) invasive breast cancer
- History of non-breast malignancies within the 5 years prior to study entry, except for carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin
- Any "clinical" T4 tumor as defined by primary tumor/regional lymph nodes/distant metastasis (TNM), including inflammatory breast cancer
- Any node-negative tumor
- Any previous systemic chemotherapy for cancer or radiotherapy for cancer
- Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy for cancer
- Concurrent anti-cancer treatment in another investigational trial
- Serious cardiac or cardiovascular disease or condition
- Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness
- Abnormal laboratory tests immediately prior to randomization
- Pregnant or lactating women
- Sensitivity to any of the study medications or any of the ingredients or excipients of these medications
Data sourced from ClinicalTrials.gov (NCT01358877) 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.