Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer

Authors: Schneeweiss, A., Chia, S., Hickish, T., Harvey, V., Eniu, A., Waldron-Lynch, M., Eng-Wong, J., Kirk, S. and Cortés, J.

Journal: European Journal of Cancer

Volume: 89

Pages: 27-35

eISSN: 1879-0852

ISSN: 0959-8049

DOI: 10.1016/j.ejca.2017.10.021

Abstract:

Background We report long-term efficacy and cardiac safety outcomes in patients with HER2-positive early breast cancer treated with neoadjuvant pertuzumab plus trastuzumab with anthracycline-containing or anthracycline-free chemotherapy. Methods Descriptive efficacy analyses were conducted in patients randomised to group A (cycles 1–6: trastuzumab [8 mg/kg loading dose and 6 mg/kg maintenance] plus pertuzumab [840 mg loading dose and 420 mg maintenance], plus 5-fluorouracil, epirubicin and cyclophosphamide [FEC] [cycles 1–3; 500 mg/m2 5-fluorouracil/100 mg/m2 epirubicin/600 mg/m2 cyclophosphamide] then docetaxel [cycles 4–6; 75 mg/m2, escalated to 100 mg/m2 if well tolerated]), B (cycles 1–3: FEC, cycles 4–6: trastuzumab plus pertuzumab plus docetaxel as mentioned previously) or C (cycles 1–6: trastuzumab plus pertuzumab plus docetaxel [75 mg/m2, without dose escalation], and carboplatin [AUC 6]), five years after randomisation of the last patient. This study is registered with ClinicalTrials.gov, number NCT00976989. Results Three-year Kaplan–Meier survival estimates for disease-free survival (DFS) were 87% (95% confidence interval: 79–95), 88% (80–96) and 90% (82–97) in groups A–C, respectively. Progression-free survival (PFS) rates were 89% (81–96), 89% (81–96) and 87% (80–95). DFS hazard ratio for total pathological complete response (tpCR) versus no tpCR was 0.27 (0.11–0.64). During post-treatment follow-up, 2/72 (2.8%), 3/75 (4.0%) and 4/76 (5.4%) patients in groups A–C had any-grade left ventricular systolic dysfunction; eight (11.1%), 12 (16.0%) and nine (11.8%) patients experienced left ventricular ejection fraction declines ≥10% from baseline to <50%. Conclusions Long-term DFS and PFS were similar between groups. Patients who achieved tpCR had improved DFS. No new safety signals were identified.

Source: Scopus

Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer.

Authors: Schneeweiss, A., Chia, S., Hickish, T., Harvey, V., Eniu, A., Waldron-Lynch, M., Eng-Wong, J., Kirk, S. and Cortés, J.

Journal: Eur J Cancer

Volume: 89

Pages: 27-35

eISSN: 1879-0852

DOI: 10.1016/j.ejca.2017.10.021

Abstract:

BACKGROUND: We report long-term efficacy and cardiac safety outcomes in patients with HER2-positive early breast cancer treated with neoadjuvant pertuzumab plus trastuzumab with anthracycline-containing or anthracycline-free chemotherapy. METHODS: Descriptive efficacy analyses were conducted in patients randomised to group A (cycles 1-6: trastuzumab [8 mg/kg loading dose and 6 mg/kg maintenance] plus pertuzumab [840 mg loading dose and 420 mg maintenance], plus 5-fluorouracil, epirubicin and cyclophosphamide [FEC] [cycles 1-3; 500 mg/m2 5-fluorouracil/100 mg/m2 epirubicin/600 mg/m2 cyclophosphamide] then docetaxel [cycles 4-6; 75 mg/m2, escalated to 100 mg/m2 if well tolerated]), B (cycles 1-3: FEC, cycles 4-6: trastuzumab plus pertuzumab plus docetaxel as mentioned previously) or C (cycles 1-6: trastuzumab plus pertuzumab plus docetaxel [75 mg/m2, without dose escalation], and carboplatin [AUC 6]), five years after randomisation of the last patient. This study is registered with ClinicalTrials.gov, number NCT00976989. RESULTS: Three-year Kaplan-Meier survival estimates for disease-free survival (DFS) were 87% (95% confidence interval: 79-95), 88% (80-96) and 90% (82-97) in groups A-C, respectively. Progression-free survival (PFS) rates were 89% (81-96), 89% (81-96) and 87% (80-95). DFS hazard ratio for total pathological complete response (tpCR) versus no tpCR was 0.27 (0.11-0.64). During post-treatment follow-up, 2/72 (2.8%), 3/75 (4.0%) and 4/76 (5.4%) patients in groups A-C had any-grade left ventricular systolic dysfunction; eight (11.1%), 12 (16.0%) and nine (11.8%) patients experienced left ventricular ejection fraction declines ≥10% from baseline to <50%. CONCLUSIONS: Long-term DFS and PFS were similar between groups. Patients who achieved tpCR had improved DFS. No new safety signals were identified.

Source: PubMed

Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer

Authors: Schneeweiss, A., Chia, S., Hickish, T., Harvey, V., Eniu, A., Waldron-Lynch, M., Eng-Wong, J., Kirk, S. and Cortes, J.

Journal: EUROPEAN JOURNAL OF CANCER

Volume: 89

Pages: 27-35

eISSN: 1879-0852

ISSN: 0959-8049

DOI: 10.1016/j.ejca.2017.10.021

Source: Web of Science (Lite)

Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer.

Authors: Schneeweiss, A., Chia, S., Hickish, T., Harvey, V., Eniu, A., Waldron-Lynch, M., Eng-Wong, J., Kirk, S. and Cortés, J.

Journal: European journal of cancer (Oxford, England : 1990)

Volume: 89

Pages: 27-35

eISSN: 1879-0852

ISSN: 0959-8049

DOI: 10.1016/j.ejca.2017.10.021

Abstract:

Background

We report long-term efficacy and cardiac safety outcomes in patients with HER2-positive early breast cancer treated with neoadjuvant pertuzumab plus trastuzumab with anthracycline-containing or anthracycline-free chemotherapy.

Methods

Descriptive efficacy analyses were conducted in patients randomised to group A (cycles 1-6: trastuzumab [8 mg/kg loading dose and 6 mg/kg maintenance] plus pertuzumab [840 mg loading dose and 420 mg maintenance], plus 5-fluorouracil, epirubicin and cyclophosphamide [FEC] [cycles 1-3; 500 mg/m2 5-fluorouracil/100 mg/m2 epirubicin/600 mg/m2 cyclophosphamide] then docetaxel [cycles 4-6; 75 mg/m2, escalated to 100 mg/m2 if well tolerated]), B (cycles 1-3: FEC, cycles 4-6: trastuzumab plus pertuzumab plus docetaxel as mentioned previously) or C (cycles 1-6: trastuzumab plus pertuzumab plus docetaxel [75 mg/m2, without dose escalation], and carboplatin [AUC 6]), five years after randomisation of the last patient. This study is registered with ClinicalTrials.gov, number NCT00976989.

Results

Three-year Kaplan-Meier survival estimates for disease-free survival (DFS) were 87% (95% confidence interval: 79-95), 88% (80-96) and 90% (82-97) in groups A-C, respectively. Progression-free survival (PFS) rates were 89% (81-96), 89% (81-96) and 87% (80-95). DFS hazard ratio for total pathological complete response (tpCR) versus no tpCR was 0.27 (0.11-0.64). During post-treatment follow-up, 2/72 (2.8%), 3/75 (4.0%) and 4/76 (5.4%) patients in groups A-C had any-grade left ventricular systolic dysfunction; eight (11.1%), 12 (16.0%) and nine (11.8%) patients experienced left ventricular ejection fraction declines ≥10% from baseline to <50%.

Conclusions

Long-term DFS and PFS were similar between groups. Patients who achieved tpCR had improved DFS. No new safety signals were identified.

Source: Europe PubMed Central