Top

Published in:

01-07-2016 | Clinical Trial

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

Authors: L. M. Smyth, N. M. Iyengar, M. F. Chen, S. M. Popper, S. Patil, C. Wasserheit-Lieblich, D. F. Argolo, J. C. Singh, S. Chandarlapaty, S. M. Sugarman, E. A. Comen, P. R. Drullinsky, T. A. Traina, T. Troso-Sandoval, J. Baselga, L. Norton, C. A. Hudis, C. T. Dang

Published in: Breast Cancer Research and Treatment | Issue 1/2016

Abstract

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

Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science (New York, NY) 235(4785):177–182CrossRef

Andrulis IL, Bull SB, Blackstein ME, Sutherland D, Mak C, Sidlofsky S, Pritzker KP, Hartwick RW, Hanna W, Lickley L et al (1998) neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group. J Clin Oncol 16(4):1340–1349PubMed

Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M et al (2001) Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2. N Engl J Med 344(11):783–792CrossRefPubMed

Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A et al (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366(2):109–119CrossRefPubMed

Hudis CA (2007) Trastuzumab— Mechanism of Action and Use in Clinical Practice. N Engl J Med 357(1):39–51CrossRefPubMed

Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX (2004) Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 5(4):317–328CrossRefPubMed

Baselga J, Swain SM (2009) Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer 9(7):463–475CrossRefPubMed

Agus DB, Akita RW, Fox WD, Lewis GD, Higgins B, Pisacane PI, Lofgren JA, Tindell C, Evans DP, Maiese K et al (2002) Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell 2(2):127–137CrossRefPubMed

Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M (2009) Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res 69(24):9330–9336CrossRefPubMed

10.

Swain SM, Kim SB, Cortes J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A et al (2013) Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 14(6):461–471CrossRefPubMedPubMedCentral

11.

Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S et al (2015) Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 372(8):724–734CrossRefPubMed

12.

Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE (2008) Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 358(16):1663–1671CrossRefPubMedPubMedCentral

13.

Dang C, Iyengar N, Datko F, D’Andrea G, Theodoulou M, Dickler M, Goldfarb S, Lake D, Fasano J, Fornier M et al (2015) Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol 33(5):442–447CrossRefPubMed

14.

Gradishar WJA, Benjamin O (2015) Balassanian, Ron Blair et al.: Breast Cancer Version 2.2015. J Natl Compr Canc Netw 13(4):448–475PubMed

15.

Yu AF, Manrique C, Pun S, Liu JE, Mara E, Fleisher M, Patil S, Jones LW, Steingart RM, Hudis CA et al (2016) Cardiac Safety of Paclitaxel Plus Trastuzumab and Pertuzumab in Patients With HER2-Positive Metastatic Breast Cancer. The Oncologist 21(4):418–424CrossRefPubMed

16.

Andersson M, López-Vega JM, Petit T, Zamagni C, Donica M, Kamber J, Perez EA (2015) The co-administration of pertuzumab (P) and trastuzumab (T) as a single infusion, followed by vinorelbine (V), in first-line (1L) treatment of HER2-positive locally advanced or metastatic breast cancer (MBC) patients (pts): VELVET study interim analysis. J Clin Oncol 33(15):586 2015 ASCO Annual Meeting

17.

Perez EA, Lopez-Vega JM, Mastro LD, Petit T, Mitchell L, Pelizon CH, Andersson M (2012) A combination of pertuzumab, trastuzumab, and vinorelbine for first-line treatment of patients with HER2-positive metastatic breast cancer: An open-label, two-cohort, phase II study (VELVET). J Clin Oncol 30(15):TPS653 2012 ASCO Annual Meeting

18.

Andersson M, Lopez-Vega JM, Petit T, Zamagni C, Freudensprung U, Robb S, Restuccia E, Perez EA (2014) 361PDINTERIM SAFETY AND EFFICACY OF PERTUZUMAB, TRASTUZUMAB AND VINORELBINE FOR FIRST-LINE (1L) TREATMENT OF PATIENTS (PTS) WITH HER2-POSITIVE LOCALLY ADVANCED OR METASTATIC BREAST CANCER (MBC). Annals of Oncology 25(4):iv120–iv120

19.

Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13(1):25–32CrossRefPubMed

20.

Amiri-Kordestani L, Wedam S, Zhang L, Tang S, Tilley A, Ibrahim A, Justice R, Pazdur R, Cortazar P (2014) First FDA approval of neoadjuvant therapy for breast cancer: pertuzumab for the treatment of patients with HER2-positive breast cancer. Clinical cancer research: an official journal of the American Association for Cancer Research 20(21):5359–5364CrossRef

21.

Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J et al (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Annals of oncology: official journal of the European Society for Medical Oncology/ESMO 24(9):2278–2284CrossRef

22.

Von Minckwitz G, Baselga J, Bradbury I, de Azambuja E, Scullion M, Ross G, Saini K, Piccart-Gebhart M (2011) Adjuvant Pertuzumab and Herceptin IN IniTial TherapY of Breast Cancer: APHINITY (BIG 4–11/BO25126/TOC4939 g). Cancer Research 71(24 Supplement):OT1-02–04

23.

A Study of Kadcyla (TrastuzumabEmtansine) Plus Perjeta (Pertuzumab) Following Anthracyclines in Comparison With Herceptin (Trastuzumab) Plus Perjeta and a Taxane Following Anthracyclines as Adjuvant Therapy in Patients With Operable HER2-Positive Primary Breast Cancer. http://clinicaltrials.gov/ct2/show/NCT01966471

24.

Ellis PA, Barrios CH, Eiermann W, Toi M, Im Y-H, Conte PF, Martin M, Pienkowski T, Pivot XB, Burris HA et al (2015) Phase III, randomized study of trastuzumab emtansine (T-DM1) ± pertuzumab (P) vs trastuzumab + taxane (HT) for first-line treatment of HER2-positive MBC: Primary results from the MARIANNE study. J Clin Oncol 33(15):507

Title: 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
Authors: L. M. Smyth
N. M. Iyengar
M. F. Chen
S. M. Popper
S. Patil
C. Wasserheit-Lieblich
D. F. Argolo
J. C. Singh
S. Chandarlapaty
S. M. Sugarman
E. A. Comen
P. R. Drullinsky
T. A. Traina
T. Troso-Sandoval
J. Baselga
L. Norton
C. A. Hudis
C. T. Dang
Publication date: 01-07-2016
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2016
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-016-3851-7

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2016

Aberrant nocturnal cortisol and disease progression in women with breast cancer

Plasma fluorescent oxidation products and risk of estrogen receptor-negative breast cancer in the Nurses’ Health Study and Nurses’ Health Study II

Preoperative breast magnetic resonance imaging and contralateral breast cancer occurrence among older women with ductal carcinoma in situ

Prognostic and predictive impacts of tumor-infiltrating lymphocytes differ between Triple-negative and HER2-positive breast cancers treated with standard systemic therapies

Palbociclib as a first-line treatment in oestrogen receptor-positive, HER2-negative, advanced breast cancer not cost-effective with current pricing: a health economic analysis of the Swiss Group for Clinical Cancer Research (SAKK)

Retrospective study of the efficacy and safety of neoadjuvant docetaxel, carboplatin, trastuzumab/pertuzumab (TCH-P) in nonmetastatic HER2-positive breast cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer