Cardiac Safety of Paclitaxel Plus Trastuzumab and Pertuzumab in Patients With HER2-Positive Metastatic Breast Cancer

Yu, Anthony F.; Manrique, Carlos; Pun, Shawn C.; Liu, Jennifer E.; Mara, Elton; Fleisher, Martin; Patil, Sujata; Jones, Lee W.; Steingart, Richard M.; Hudis, Clifford A.; Dang, Chau T.

doi:10.1634/theoncologist.2015-0321

Cited by 46 publications

(40 citation statements)

References 35 publications

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“…Cardiac safety was defined as symptomatic left ventricular systolic dysfunction (LVSD), non-LVSD cardiac death, or probable cardiac death. Cardiac biomarkers were explored (previously reported) [15]. Herein, we report the median OS and updated PFS results.…”

Section: Methodsmentioning

confidence: 99%

Weekly paclitaxel with trastuzumab and pertuzumab in patients with HER2-overexpressing metastatic breast cancer: overall survival and updated progression-free survival results from a phase II study

Smyth

Iyengar

Chen

et al. 2016

Breast Cancer Res Treat

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We previously reported progression-free survival (PFS) results on a phase II trial of weekly paclitaxel, trastuzumab, and pertuzumab in patients with human epidermal growth factor receptor 2(HER2)–positive metastatic breast cancer (MBC) treated in the first- and second-line setting. Here, we report results for overall survival (OS) and updated PFS after an additional year of follow-up. Patients with HER2-positive MBC with 0–1 prior treatment were eligible. Treatment consisted of paclitaxel (80 mg/m2) weekly, and trastuzumab (loading dose 8 mg/kg → 6 mg/kg) and pertuzumab (loading dose 840 mg → 420 mg) every 3 weeks, all given intravenously. Primary endpoint was 6-month PFS. Secondary endpoints included median PFS, 6-month and median OS. Evaluable patients received at least one full dose of treatment. From January 2011 to December 2013, 69 patients were enrolled: 51 (74 %) and 18 (26 %) treated in first- and second-line metastatic settings, respectively. As of July 1, 2015, the median follow-up was 33 months (range 3–49 months; 67 patients were evaluable for efficacy). The median OS was 44 months (95 % CI 37.5–NR) overall and 44 months (95 % CI 38.3–NR) and 37.5 months (95 % CI 30.3–NR) for patients with 0 and 1 prior metastatic treatment, respectively; 6-month OS was 98 % (95 % CI 90-1). The 6-month PFS was 86 % (95 % CI 75–93) overall and 89 % (95 % CI 76–95) and 78 % (95 % CI 51–91) for patients with 0 and 1 prior therapy, respectively; and median PFS was 21.4 months (95 % CI 14.1–NR) overall and 25.7 months (95 % CI 14.1–NR) and 16.9 months (95 % CI 8.5–NR) for patients with 0–1 prior treatment, respectively. Treatment was well tolerated. Updated analysis demonstrates that weekly paclitaxel, when added to trastuzumab and pertuzumab, is associated with a favorable OS and PFS and offers an alternative to docetaxel-based therapy. http://www.ClinicalTrials.gov NCT0127604

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Section: Methodsmentioning

confidence: 99%

Weekly paclitaxel with trastuzumab and pertuzumab in patients with HER2-overexpressing metastatic breast cancer: overall survival and updated progression-free survival results from a phase II study

Smyth

Iyengar

Chen

et al. 2016

Breast Cancer Res Treat

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“…There is no consensus regarding frequency or duration of screening in this population, and recommendations have ranged widely and generally depend on cumulative anthracycline dose and history of radiation therapy . To implement cardioprotective strategies and limit the risk of cardiac toxicity, there is developing interest in sensitive and specific markers of early LV dysfunction including advanced imaging modalities and cardiac biomarkers …”

Section: Introductionmentioning

confidence: 99%

Electrophysiological effects of anthracyclines in adult survivors of pediatric malignancy

Markman

Ruble

Loeb

et al. 2017

Pediatric Blood & Cancer

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“…With further follow‐up at 33 months, the median OS was 44 months . As expected, the regimen was well tolerated with 0% symptomatic left ventricular systolic dysfunction (LVSD) and 0% incidence of neutropenic fever . Furthermore, no additional incidence of LVSD or neutropenic fever occurred .…”

Section: Introductionmentioning

confidence: 53%

“…As expected, the regimen was well tolerated with 0% symptomatic left ventricular systolic dysfunction (LVSD) and 0% incidence of neutropenic fever . Furthermore, no additional incidence of LVSD or neutropenic fever occurred . This regimen has been endorsed by the National Comprehensive Cancer Network guidelines as an option for patients with HER2‐positive metastatic breast cancer in the first‐line treatment .…”

Section: Introductionmentioning

confidence: 54%

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Phase II Study of Weekly Paclitaxel with Trastuzumab and Pertuzumab in Patients with Human Epidermal Growth Receptor 2 Overexpressing Metastatic Breast Cancer: 5-Year Follow-up

et al. 2019

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Background Favorable progression‐free survival (PFS) and overall survival (OS) results were previously reported on a phase II trial of patients with human epidermal growth receptor 2 (HER2)‐positive metastatic breast cancer (MBC), treated with weekly paclitaxel in combination with trastuzumab and pertuzumab in the first‐ and second‐line setting, with a median follow‐up of 33 months. Here, we report updated PFS and OS results with more than 2 years of additional follow‐up. Materials and Methods In this phase II study, adult patients with HER2‐positive MBC who received no or one prior therapy received intravenous paclitaxel (80 mg/m2 weekly) with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks) and pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks), administered in 21‐day cycles. Primary endpoint was 6‐month PFS, and secondary endpoints included median PFS and OS. Results From January 2011 to December 2013, 69 patients were enrolled: 51 (74%) and 18 (26%) were treated in first‐ and second‐line metastatic settings, respectively. As of August 21, 2017, the median follow‐up was 59 months (range, 20–75 months; 67 [97%] patients were evaluable for efficacy). The 6‐month PFS was 86% (95% confidence interval [CI] 0.76–0.93). The median PFS was 24.2 months (95% CI 17–35) for the overall population; it was 25.7 months (95% CI 17.0 to not reached) and 20.1 months (95% CI 8.5–33.0) for patients with no and one prior treatment, respectively. The median OS was not reached for the overall group; it was not reached and 39.7 months (95% CI 32.9–66.7) for patients with no and one prior treatment, respectively. Treatment was well tolerated with no additional safety concerns. Conclusion With a longer follow‐up of almost 5 years, combination of weekly paclitaxel, trastuzumab, and pertuzumab remains effective with a favorable median PFS and a median OS not reached. Implications for Practice The combination of weekly paclitaxel, trastuzumab, and pertuzumab has been endorsed by the National Comprehensive Cancer Network as one of the first‐line treatment options in patients with human epidermal growth receptor 2 (HER2)‐positive metastatic breast cancer (MBC). However, the long‐term safety and efficacy are still unknown. Findings from this phase II study provide favorable preliminary data on the safety and efficacy of trastuzumab and pertuzumab in combination with weekly paclitaxel at 5‐year follow‐up, and it remains an effective first‐line treatment option for patients with HER2‐positive MBC.

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Cardiac Safety of Paclitaxel Plus Trastuzumab and Pertuzumab in Patients With HER2-Positive Metastatic Breast Cancer

Cited by 46 publications

References 35 publications

Weekly paclitaxel with trastuzumab and pertuzumab in patients with HER2-overexpressing metastatic breast cancer: overall survival and updated progression-free survival results from a phase II study

Weekly paclitaxel with trastuzumab and pertuzumab in patients with HER2-overexpressing metastatic breast cancer: overall survival and updated progression-free survival results from a phase II study

Electrophysiological effects of anthracyclines in adult survivors of pediatric malignancy

Phase II Study of Weekly Paclitaxel with Trastuzumab and Pertuzumab in Patients with Human Epidermal Growth Receptor 2 Overexpressing Metastatic Breast Cancer: 5-Year Follow-up

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