Notification

Trastuzumab (Herceptin®) and Related Biosimilars, Trastuzumab and Hyaluronidase-oysk (Herceptin Hylecta)


Notification Issue Date: 02/13/2020



Policy Attachment



Attachment to Policy # 08.00.33o


Attachment:A

Policy #:08.00.33o

Description:Dosing & Frequency Requirements for Trastuzumab (Herceptin®) and Related Biosimilars, Trastuzumab and hyaluronidase-oysk (Herceptin Hylecta)

Title:Trastuzumab (Herceptin®) and Related Biosimilars, Trastuzumab and Hyaluronidase-oysk (Herceptin Hylecta)



DOSING AND FREQUENCY REQUIREMENTS FOR TRASTUZUMAB (HERCEPTIN®) and related biosimilars (e.g., trastuzumab-pkrb [Herzuma®], trastuzumab-dkst [Ogivri™], trastuzumab-dttb, [Ontruzant®], trastuzumab-qyyp [Trazimera] )

BREAST CANCER
Preoperative (Neoadjuvant)ChemotherapyPreoperative (neoadjuvant) chemotherapy for individuals with HER2-positive breast cancer:
  • In those who have locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive):
    • In combination with (neoadjuvant) pertuzumab (Perjeta®) and chemotherapy56
      • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
        Initial dose at 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks
        • 1 dose 8 mg/kg
        • 17 doses 6 mg/kg
  • In those who have stage stage IIA (T0, N1, M0 or T1, N1, M0 or T2, N0, M0), stage IIB (T2, N1, M0 or T3, N0, M0), or stage IIIA (T3, N1, M0) breast cancer who desire breast preservation and fulfill the criteria for breast-conserving surgery, except for tumor size, or for those who have node-positive disease likely to become node-negative with preoperative systemic therapy, or for individuals with locally advanced disease (stage IIIA (any T, N2, M0), IIIB, or IIIC):
    • Concurrently with paclitaxel following AC (doxorubicin and cyclophosphamide) with or without pertuzumab (Perjeta®) 6, 29, 37
      • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
        • With weekly paclitaxel
          Initial dose of 4 mg/kg followed by 51 weekly doses of 2 mg/kg
          • 1 dose 4 mg/kg
          • 51 doses 2 mg/kg
        OR
        Initial dose of 4 mg/kg followed by 11 weekly doses of 2 mg/kg; subsequent 14 doses at 6 mg/kg every 3 weeks starting on week 13 through week 52
          • 1 dose 4 mg/kg
          • 11 doses 2 mg/kg
          • 14 doses 6 mg/kg
        • With paclitaxel every 14 days following dose dense AC (doxorubicin and cyclophosphamide)6, 29
          Initial dose of 4 mg/kg followed by 7 weekly doses of 2 mg/kg; subsequent 15 doses at 6 mg/kg every 3 weeks starting on week 9 through week 52
OR
        • With paclitaxel and pertuzumab (Perjeta®) every 21 days following AC (doxorubicin and cyclophosphamide)6, 29
          Initial dose at 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks
          • 1 dose 8 mg/kg
          • 17 doses 6 mg/kg
  • In TCH (docetaxel, carboplatin, and trastuzumab) regimen 6, 29, 30, 60
      • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
        Initial dose of 4 mg/kg followed by 17 weekly doses of 2 mg/kg; subsequent 12 doses at 6 mg/kg every 3 weeks starting on week 19 through week 52
  • In TCH (docetaxel, carboplatin, and trastuzumab) regimen with pertuzumab (Perjeta®) 6, 29, 60
      • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
        Initial dose at 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks
        • 1 dose 8 mg/kg
        • 17 doses 6 mg/kg
  • In combination with docetaxel following AC regimen6, 29, 40, 42, 60
      • Trastuzumab (Herceptin®) and related biosimilars :
        Initial dose of 4 mg/kg followed by 11 weekly doses of 2 mg/kg; subsequent 14 doses at 6 mg/kg every 3 weeks starting on week 13 through week 52
        • 1 dose 4 mg/kg
        • 11 doses 2 mg/kg
        • 14 doses 6 mg/kg
  • In combination with docetaxel and pertuzumab (Perjeta®) following AC regimen 6, 29
      • Trastuzumab (Herceptin®) and related biosimilars :
        Initial dose at 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks
        • 1 dose 8 mg/kg
        • 17 doses 6 mg/kg
  • In combination with docetaxel and cyclophosphamide 6, 29
      • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
        Initial dose of 4 mg/kg, then 11 weekly doses of 2 mg/kg, followed by 14 doses of 6 mg/kg administered every 21 days
        • 1 dose 4 mg/kg
        • 11 doses 2 mg/kg
        • 14 doses 6 mg/kg
        OR
        Initial dose at 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks
        • 1 dose 8 mg/kg
        • 17 doses 6 mg/kg
Adjuvant Treatment For adjuvant treatment of HER-2-overexpressing node-positive or node-negative breast cancer (ER/PR negative or with one high-risk feature) breast cancer as part of any of the following treatment regimens:
  • In combination with AC (doxorubicin and cyclophosphamide) and either paclitaxel or docetaxel
    • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
      • With weekly paclitaxel following AC (doxorubicin and cyclophosphamide)1, 6, 28, 29, 37, 52
        Initial dose of 4 mg/kg followed by 11 weekly doses of 2 mg/kg; subsequent 14 doses at 6 mg/kg every 3 weeks starting on week 13 through week 52
      • With paclitaxel every 14 days following dose dense AC (doxorubicin and cyclophosphamide) 6, 29, 61
        Initial dose of 4 mg/kg followed by 7 weekly doses of 2 mg/kg; subsequent 15 doses at 6 mg/kg every 3 weeks starting on week 9 through week 52
      • With docetaxel every 21 days1, 6, 28, 29, 37, 40, 42, 52, 60
        Initial dose of 4 mg/kg followed by 11 weekly doses of 2 mg/kg; subsequent 14 doses at 6 mg/kg every 3 weeks starting on week 13 through week 52
  • In TCH (docetaxel, carboplatin, and trastuzumab) regimen1, 6, 28, 29, 30, 52, 60
    • Trastuzumab (Herceptin®) and related biosimilars (Herceptin®) for a total of 52 weeks:
      Initial dose of 4 mg/kg followed by 17 weekly doses of 2 mg/kg; subsequent 12 doses at 6 mg/kg every 3 weeks starting on week 19 through week 52
  • As a single agent within 3 weeks following multi-modality anthracycline-based therapy1,28, 52
    • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
      Initial dose at 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks
      • 1 dose 8 mg/kg
      • 17 doses 6 mg/kg
  • In combination with pertuzumab (Perjeta®) and either docetaxel or paclitaxel following AC regimen29
    • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
      Initial dose at 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks
      • 1 dose 8 mg/kg
      • 17 doses 6 mg/kg

Adjuvant treatment of individuals with HER2-positive stage I, IIA, IIB, or IIIA (T3, N1, M0) disease (ductal, lobular, mixed, or metaplastic histologies), or for locally advanced disease (stage IIIA (any T, N2, M0), IIIB, or IIIC).
  • In combination with paclitaxel following AC (doxorubicin and cyclophosphamide) regimen as an NCCN-preferred regimen 6, 29, 37
    • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
      Initial dose of 4 mg/kg, then 51 weekly doses of 2 mg/kg
      • 1 dose 4 mg/kg
      • 51 doses 2 mg/kg
      OR
      Initial dose of 4 mg/kg, then 11 weekly doses of 2 mg/kg, followed by 14 doses of 6 mg/kg administered every 21 days
      • 1 dose 4 mg/kg
      • 11 doses 2 mg/kg
      • 14 doses 6 mg/kg
  • In combination with paclitaxel following dose dense AC (doxorubicin and cyclophosphamide)6, 29, 61
    • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
      Initial dose of 4 mg/kg followed by 7 weekly doses of 2 mg/kg; subsequent 15 doses at 6 mg/kg every 3 weeks starting on week 9 through week 52
      • 1 dose 4 mg/kg
      • 7 doses 2 mg/kg
      • 15 doses 6 mg/kg
  • In TCH (docetaxel, carboplatin, and trastuzumab) regimen as an NCCN-preferred regimen 1, 6, 29, 60
    • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
      Initial dose of 4 mg/kg followed by 17 weekly doses of 2 mg/kg; subsequent 12 doses at 6 mg/kg every 3 weeks starting on week 19 through week 52
      • 1 dose 4 mg/kg
      • 17 doses 2 mg/kg
      • 12 doses 6 mg/kg
  • In combination with docetaxel following AC (doxorubicin and cyclophosphamide) regimen 6, 29, 40, 60
    • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
      Initial dose of 4 mg/kg, then 11 weekly doses of 2 mg/kg, followed by 14 doses of 6 mg/kg administered every 21 days
      • 1 dose 4 mg/kg
      • 11 doses 2 mg/kg
      • 14 doses 6 mg/kg
  • In combination with docetaxel and cyclophosphamide 6, 29
    • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
      Initial dose at 8 mg/kg, then subsequent doses at 6 mg/kg every 3 weeks
      • 1 dose 8 mg/kg
      • 17 doses 6 mg/kg
      OR
      Initial dose of 4 mg/kg, then 11 weekly doses of 2 mg/kg, followed by 14 doses of 6 mg/kg administered every 21 days
      • 1 dose 4 mg/kg
      • 11 doses 2 mg/kg
      • 14 doses 6 mg/kg
  • In TCH regimen (as an NCCN-preferred regimen) with pertuzumab (Perjeta®)6, 29
    • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
      Initial dose at 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks
      • 1 dose 8 mg/kg
      • 17 doses 6 mg/kg
  • In combination with pertuzumab (Perjeta®) and paclitaxel (as an NCCN-preferred regimen) or pertuzumab (Perjeta®) and docetaxel following AC regimen6, 29
    • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
      Initial dose at 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks
      • 1 dose 8 mg/kg
      • 17 doses 6 mg/kg

Adjuvant treatment of individuals with HER2-positive, low risk stage I breast cancer
  • In combination with paclitaxel (particularly for individuals not eligible for other standard adjuvant regimens due to comorbidities) 6, 29
    • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
      Initial dose of 4 mg/kg, then 51 weekly doses of 2 mg/kg
      • 1 dose 4 mg/kg
      • 51 doses 2 mg/kg
      OR
      Initial dose of 4 mg/kg, then 11 weekly doses of 2 mg/kg, followed by 6 mg/kg every 21 days for 14 doses.
      • 1 dose 4 mg/kg
      • 11 doses 2 mg/kg
      • 14 doses 6 mg/kg

Adjuvant treatment of individuals with HER2-positive early breast cancer at high risk of recurrence
  • In combination with pertuzumab (Perjeta®) and chemotherapy
    • Trastuzumab (Herceptin®) and related biosimilars for a total of 52 weeks:
      Initial dose at 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks
      • 1 dose 8 mg/kg
      • 17 doses 6 mg/kg
Recurrent or Metastatic Breast Cancer



















As a single agent for the treatment of HER2-overexpressing breast cancer in individuals who have received one or more chemotherapy regimens metastatic disease
      • Trastuzumab (Herceptin®) and related biosimilars
        Initial dose of 4 mg/kg; subsequent doses at 2 mg/kg weekly until disease progression or unacceptable toxicity

In combination with tamoxifen, fulvestrant, or aromatase inhibitors (e.g., anastrozole [Arimidex®], exemestane [Aromasin®], letrozole [Femara®] with or without lapatinib [Tykerb®] for the treatment of recurrent or stage IV estrogen receptor-positive, human epidermal growth factor receptor 2 (HER-2)-positive disease in postmenopausal women* 6, 29, 32
      *Men with breast cancer should be treated similarly to postmenopausal women, except that use of an aromatase inhibitor is ineffective without concomitant suppression of testicular steroidogenesis
      • Trastuzumab (Herceptin®) and related biosimilars
        Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity
In combination with tamoxifen for the treatment of recurrent or stage IV estrogen receptor-positive, HER2-positive disease in premenopausal women*
      *Men with breast cancer should be treated similarly to postmenopausal women, except that use of an aromatase inhibitor is ineffective without concomitant suppression of testicular steroidogenesis
      • Trastuzumab (Herceptin®) and related biosimilars
        Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity

In combination with pertuzumab (Perjeta)and docetaxel for the treatment of individuals with HER2-positive disease who have not received prior anti-HER2 therapy or chemotherapy
      • Trastuzumab (Herceptin®) and related biosimilars
        Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity
      OR
      Initial dose of 4 mg/kg; subsequent doses at 2 mg/kg weekly until disease progression or unacceptable toxicity

For individuals with HER2-positive recurrent or metastatic breast cancer that is either hormone receptor-negative, hormone receptor-positive and endocrine therapy refractory, with symptomatic visceral disease, or visceral crisis:
  • First-line therapy in combination with pertuzumab (Perjeta®) with docetaxel or paclitaxel
      • Trastuzumab (Herceptin®) and related biosimilars :
        • With docetaxel6, 29,56,57
          Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity
        • With paclitaxel
          Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity
  • In combination with docetaxel, vinorelbine, or capecitabine; or with paclitaxel with or without carboplatin
      • Trastuzumab (Herceptin®) and related biosimilars : 1, 6, 29, 41
        • With docetaxel weekly or every 21 days6, 26, 29, 43, 44, 55
          Initial dose of 4 mg/kg followed by weekly doses of 2 mg/kg until disease progression or unacceptable toxicity
      OR
        Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity

        • With vinorelbine6, 29, 33, 36, 39, 45, 62
          Initial dose of 4 mg/kg followed by weekly doses of 2 mg/kg until disease progression or unacceptable toxicity
        OR

        Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity

        • With capecitabine6, 8, 26, 29, 33, 35, 36, 39, 50, 58
          Initial dose of 4 mg/kg followed by weekly doses of 2 mg/kg until disease progression or unacceptable toxicity
        OR

        Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity

        • With paclitaxel and carboplatin (weekly or every 21 days)6, 26, 29,46, 47
          Initial dose of 4 mg/kg followed by weekly doses of 2 mg/kg until disease progression or unacceptable toxicity
        OR

        Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity

        • With Paclitaxel (weekly or every 21 days)1, 6, 8, 26, 29, 48
          Initial dose of 4 mg/kg followed by weekly doses of 2 mg/kg until disease progression or unacceptable toxicity
        OR

        Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity
  • As treatment for trastuzumab-exposed HER2-positive disease in combination with lapatinib (without cytotoxic therapy), capecitabine, carboplatin, cyclophosphamide, eribulin, gemcitabine, ixabepilone, paclitaxel, docetaxel, vinorelbine, or albumin-bound paclitaxel
      • Trastuzumab (Herceptin®) and related biosimilars :
        Initial dose of 4 mg/kg followed by weekly doses of 2 mg/kg until disease progression or unacceptable toxicity

        OR

        Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity
  • In combination with pertuzumab (Perjeta®) with or without cytotoxic therapy (eg, vinorelbine or taxane) for one line of therapy beyond first-line therapy in patients previously treated with chemotherapy and trastuzumab in the absence of pertuzumab
      • Trastuzumab (Herceptin®) and related biosimilars :
        • With pertuzumab6, 29, 57, 59
          Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity

CENTRAL NERVOUS SYSTEM METASTASES

Leptomeningeal Metastases from Breast Cancer
  • Primary treatment of individuals with normal CSF flow or no clinical evidence of abnormal flow
  • As maintenance therapy for individuals with negative CSF cytology or for clinically stable individuals with persistently positive CSF cytology
  • Therapy for individuals with positive CSF cytology
    • Trastuzumab (Herceptin®) and related biosimilars as intracerebrospinal fluid (CSF) treatment 6, 63, 64
      Doses range from 20 - 100 mg weekly or every other week


GASTRIC, ESOPHAGEAL, OR ESOPHAGOGASTRIC JUNCTION CANCER

Metastatic Gastric, Esophageal, or Esophago- gastric Junction CancerFor the palliative treatment of individuals with Karnofsky performance score of 60% or greater, or ECOG performance score of 2 or less who have advanced HER2 protein overexpressing gastric adenocarcinoma, esophageal adenocarcinoma, or esophagogastric junction adenocarcinoma, in combination with cisplatin and either fluorouracil or capecitabine as first-line therapy 6, 9, 10, 11, 12, 31, 53, 65
    • Trastuzumab (Herceptin®) and related biosimilars
      Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity


UTERINE NEOPLASMS

Endometrial CarcinomaFor primary stage III or IV or recurrent HER2-positive disease with carboplatin (area under the curve [AUC] 5) and paclitaxel 175 mg/m2 every 21 days for 6 cycles71 with
  • trastuzumab at 8 mg/kg for the first dose and 6 mg/kg in subsequent cycles, followed by trastuzumab maintenance of 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity


DOSING AND FREQUENCY REQUIREMENTS FOR TRASTUZUMAB (HERCEPTIN®) AND HYALURONIDASE-OYSK ( HERCEPTIN HYLECTA)

BREAST CANCER

Metastatic Breast CancerFor adjuvant treatment with HER2 overexpression 66,69,70
    • 600 mg trastuzumab/10,000 units hyaluronidase subQ every 3 weeks, for 52 weeks (1 year) or until disease recurrence, whichever occurs first; extending treatment beyond 1 year is not recommended.

For metastatic breast cancer with HER2 overexpression as first-line treatment in combination with paclitaxel
    • 600 mg trastuzumab/10,000 units hyaluronidase subQ every 3 weeks until disease progression

For metastatic breast cancer with HER2 overexpression as a monotherapy in individuals, who have received at least 1 prior chemotherapy regimen
    • 600 mg trastuzumab/10,000 units hyaluronidase subQ every 3 weeks until disease progression

The Company reserves the right to modify the Dosing and Frequency Guidelines listed in this Policy to ensure consistency with the most recently published recommendations for the use of trastuzumab (Herceptin®) and related biosimilars . The professional provider must supply supporting documentation (ie, published peer-reviewed literature) in order to request coverage for an amount of trastuzumab (Herceptin®) and related biosimilars in excess of the Dosing and Frequency Guidelines listed in this Policy.

Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); drug manufacturer’s guidelines; Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. For a list of Company-recognized pharmacology compendia and criteria for peer-reviewed clinical research, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for trastuzumab (Herceptin®) and related biosimilars.


REFERENCES FOR DOSING INFORMATION

1. US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Trastuzumab (Herceptin®). 02/2019. Trastuzumab and trastuzumab-pkrb Herzuma® 12/2018. Trastuzumab-dttb, Ontruzant® 01/2019. Trastuzumab-qyyp Trazimera™ 03/2019. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed Accessed April 22, 2019.

2. Elsevier's Clinical Pharmacology Compendium.Trastuzumab (Herceptin®). 01/23/2019. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed April 22, 2019.

3. Yan L, Hsu K, & Beckman RA. Antibody-based therapy for solid tumors. Cancer J. 2008 May-Jun;14(3):178-83.

4. Mauri D, Polyzos NP, Salanti G, Pavlidis N, & Ioannidis JP. Multiple-treatments meta-analysis of chemotherapy and targeted therapies in advanced breast cancer. J Natl Cancer Inst. 2008 Dec 17;100(24):1780-91. Epub 2008 Dec 9.

5. Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, & Theriault RL et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005 Jun 1;23(16):3676-85. Epub 2005 Feb 28.

6. National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Trastuzumab (Herceptin®). [NCCN Web site]. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed April 22, 2019.

7. Dawood S, Gonzalez-Angulo AM, Peintinger F, Broglio K, Symmans WF, & Kau SW et al. Efficacy and safety of neoadjuvant trastuzumab combined with paclitaxel and epirubicin: a retrospective review of the M. D. Anderson experience. Cancer. 2007 Sep 15;110(6):1195-200.

8. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92.

9. Van Cutsem E, Kang Y, Chung H, et al. Efficacy results from the ToGA trial: a Phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC). J Clin Oncol 2009;27. ASCO Abstract #LBA4509.

10. Van Cutsem E, Kang Y-K, Chung HC, et al. Efficacy results from the ToGA trial: a Phase III study of trastuzumab added to standard chemotherapy in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. Presented at the 45th Annual Meeting of the American Society of Clinical Oncology in Orlando, Florida; May 29 - June 2, 2009. ASCO Oral Presentation #LBA4509.

11.Van Cutsem E, Kang Y-K, Shen L, et al. Trastuzumab added to standard chemotherapy as first-line treatment in HER2-positive advanced gastric cancer: efficacy and safety results from the Phase III ToGA trial. Presented at the 34th Eurpoean Society for Medical Oncology Congress in Berlin, Germany; September 20 - 24, 2009. ESMO Oral presentation.

12. Genentech Medical Communications, (Genentech@druginfo.com), May 11th, 2010. Medical Information Requested on Herceptin From Genentech.

13. Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, & Theriault RL et al. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007 Jan 1;13(1):228-33.

14. Chang JC. HER2 inhibition: from discovery to clinical practice. Clin Cancer Res. 2007 Jan 1;13(1):1-3.

15. Woodward EJ & Twelves C. Scheduling of Taxanes: A Review. Curr Clin Pharmacol. 2010 Apr 21. [Epub ahead of print]

16. Levęque D, Gigou L, & Bergerat JP. Clinical pharmacology of trastuzumab. Curr Clin Pharmacol. 2008 Jan;3(1):51-5.

17. Nicolini A, Giardino R, Carpi A, Ferrari P, Anselmi L, & Colosimo S et al. Metastatic breast cancer: an updating. Biomed Pharmacother. 2006 Nov;60(9):548-56. Epub 2006 Aug 28.

18. Pegram MD, Konecny GE, O'Callaghan C, Beryt M, Pietras R, & Slamon DJ. Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer. J Natl Cancer Inst. 2004 May 19;96(10):739-49.

19. Bullock K & Blackwell K. Clinical efficacy of taxane-trastuzumab combination regimens for HER-2-positive metastatic breast cancer. Oncologist. 2008 May;13(5):515-25.

20. Roukos DH. Targeting gastric cancer with trastuzumab: new clinical practice and innovative developments to overcome resistance. Ann Surg Oncol. 2010 Jan;17(1):14-7. Epub 2009 Oct 20.

21. Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, & Fleig WE. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2010 Mar 17;3:CD004064.

22. Meza-Junco J, Au HJ, & Sawyer MB. Trastuzumab for gastric cancer. Expert Opin Biol Ther. 2009 Dec;9(12):1543-51.

23. Hede K. Gastric cancer: trastuzumab trial results spur search for other targets. J Natl Cancer Inst. 2009 Oct 7;101(19):1306-7. Epub 2009 Sep 15.

24. Javle M & Hsueh CT. Recent advances in gastrointestinal oncology--updates and insights from the 2009 annual meeting of the American society of clinical oncology. J Hematol Oncol. 2010 Mar 23;3:11.

25. Vici P, Viola G, Botti C, Rossi S, Vitucci C, & Corsetti S et al. Docetaxel in the adjuvant therapy of HER-2 positive breast cancer patients. Clin Ter. 2008 Nov-Dec;159(6):449-52.

26. Leyland-Jones B, Gelmon K, Ayoub JP, Arnold A, Verma S, Dias R, Ghahramani P. Pharmacokinetics, safety, and efficacy of trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol. 2003 Nov 1;21(21):3965-71. Epub 2003 Sep 24.

27. Genentech, Inc. Trastuzumab (Herceptin) Web Site. 2018. Available at: http://www.herceptin.com/index.jsp. Accessed April 22, 2019.

28. Slamon D, Eiermann W, Robert N, et al. BCIRG 006: 2nd interim analysis phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab with docetaxel, carboplatin and trastuzumab in Her2neu positive early breast cancer patients (abstract 52). San Antonio Breast Cancer Symposium 2006.

29. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Breast Cancer. V1.2019. [NCCN Web site]. 03/14/2019. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf [via free subscription]. Accessed April 22, 2019.

30. Slamon D, Eiermann W, Robert N et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab with docetaxel, carboplatin and trastuzumab in HER2 positive early breast cancer patients:
BCIRG 006 study. Breast Cancer Res Treat 2005; 94: S5 (Abstr 1).

31. Bang YJ, Van Cutsem E, Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19.

32. Kaufman B, Mackey JR, Clemens MR et al. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28.

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