Clinical UM Guideline

 

Subject: Pertuzumab (Perjeta®)
Guideline #: CG-DRUG-72 Publish Date:    12/27/2017
Status: New Last Review Date:    11/02/2017

Description

This document address pertuzumab (Perjeta, Genentech, Inc., San Francisco, CA), a recombinant humanized monoclonal antibody that targets the human epidermal growth factor receptor 2 protein (HER2).

Note: For additional information, please refer to the following related document:

Clinical Indications

Medically Necessary:

Pertuzumab is considered medically necessary for treatment of individuals who meet criteria A and either B or C below:

  1. The breast tumor is HER2-positive (HER2+) as documented by one of the following:
    1. Immunohistochemistry (IHC) is 3+; or
    2. In situ hybridization (ISH) positive by any of the following:
      1. Single probe average HER2 copy number greater than or equal to 6.0 signals/cell; or
      2. Dual-probe HER2/CEP 17 ratio greater than or equal to 2.0; or
      3. Dual-probe HER2/CEP17 ratio less than 2.0 with an average HER2 copy number greater than or equal to 6.0 signals/cell;
        and
  2. The individual has metastatic breast cancer and both of the following:
    1. Pertuzumab will be used in combination with trastuzumab and either docetaxel* or paclitaxel*; and
    2. The combination chemotherapy with pertuzumab will be used as single-line anti-HER2 chemotherapy for metastatic disease until progression;
      *Note: If docetaxel or paclitaxel treatment is contraindicated upon initiation or discontinued (for example, related to toxicity), treatment with pertuzumab and trastuzumab may continue.
      or
  3. The individual has early stage, locally advanced, or inflammatory breast cancer and all of the following are met:
    1. Will undergo neoadjuvant (prior to surgery) therapy or adjuvant systemic therapy; and
    2. Primary tumor is larger than 2 cm in diameter or individual is lymph node positive (for neoadjuvant therapy: clinically evident by palpation or imaging); and
    3. ECOG performance status 0-2; and
    4. Used in combination therapy with trastuzumab and one of the following:
      1. Docetaxel with or without carboplatin; or
      2. Paclitaxel; and
    5. Pertuzumab is used for a maximum of 18 cycles (12 month course).

Not Medically Necessary:

Pertuzumab is considered not medically necessary for treatment of individuals who do not meet the criteria listed above.

Pertuzumab is considered not medically necessary if it is administered after trastuzumab is discontinued or as part of a regimen without trastuzumab.

Concomitant use of pertuzumab with other targeted biologic agents not otherwise noted in the criteria above (including, but not limited to erlotinib, cetuximab, panitumumab, bevacizumab, lapatinib, and ziv-aflibercept) is considered not medically necessary.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

 

J9306

Injection, pertuzumab, 1 mg [Perjeta]

 

 

ICD-10 Diagnosis

 

 

C50.011-C50.929

Malignant neoplasm of breast

 

C79.81

Secondary malignant neoplasm of breast

 

D05.00-D05.92

Carcinoma in situ of breast

 

Z85.3

Personal history of malignant neoplasm of breast

 

Discussion/General Information

Breast cancer is a type of tumor comprised of malignant (cancerous) cells that start to grow in the breast and may spread (metastasize) to surrounding tissues and other areas of the body (American Cancer Society, 2016). Breast cancer is commonly treated by various modalities which include combinations of surgery, radiation therapy, chemotherapy and hormone therapy (National Cancer Institute, 2017). The prognosis and selection of therapies can be affected by clinical and pathologic features of the tumor. One of these includes the human epidermal growth factor receptor 2 gene ERBB2 which is commonly referred to as HER2. Other names for this gene include NEU, Her-2, HER-2/neu and c-erb B2. Initially, the HER2 gene was detected in frozen breast tumor samples. Amplification of the HER2 gene was later correlated to overexpression of protein levels in samples of breast cancer. The HER2 overexpression is present in approximately 18%-25% of all early breast cancers and is associated with aggressive disease, shortened disease-free survival (DFS) and overall survival (OS) (Wolff, 2007).

Pertuzumab is a type of targeted cancer therapy that is directed towards the HER2 marker on the cancer cell. Pertuzumab interrupts the communication pathway involved in the growth and progression of the cancer cells in the tumor.

Pertuzumab is produced by recombinant deoxyribonucleic acid (DNA) technology in a mammalian cell (Chinese Hamster Ovary) culture containing the gentamycin antibiotic (Product Information Label, 2017). Pertuzumab inhibits the HER2 signaling pathways which can result in the arrest of tumor cell growth as well as cell death. Pertuzumab also mediates antibody-dependent cell-mediated cytotoxicity (ADCC). As a single agent, pertuzumab inhibited the growth of human tumor cells, while the combination of pertuzumab and trastuzumab had complementary mechanisms of action and resulted in enhanced antitumor activity (Baselga, 2012; Product Information Label, 2017).

The U.S. Food and Drug Administration (FDA) provided an accelerated approval in 2013, for the use of pertuzumab in combination with trastuzumab and docetaxel as neoadjuvant treatment for individuals with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node-positive) as part of a complete treatment regimen for early breast cancer. The approval was based on improvement of the primary endpoint of pathological complete response (pCR) in the breast, which was defined as the absence of invasive neoplastic cells at microscopic examination of the primary tumor at surgery (Gianni, 2011; Product Information Label, 2017). The label reported “No data are available demonstrating improvement in event-free survival or overall survival.” Additional information from the Product Information Label (2017) includes the following:

Limitations of Use:

Adjuvant therapy and Neoadjuvant therapy, early breast cancer
The neoadjuvant trial entry criteria included HER2-positivity, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The phase II trial included a total of 417 participants who were randomized to one of four neoadjuvant cycles: Group A treated with trastuzumab + docetaxel; Group B treated with pertuzumab, trastuzumab + docetaxel; Group C treated with pertuzumab + trastuzumab; Group D treated with pertuzumab + docetaxel. Four cycles of neoadjuvant therapy were provided and eligible participants proceeded on to surgery. Adjuvant therapy consisted of fluorouracil, epirubicin and cyclophosphamide (FEC) except Group C which received docetaxel + FEC. A significantly improved pCR rate was observed in Group B, 45.8% (95% confidence interval [CI], 36.1-55.7) vs. 29% in Group A (95% CI, 20.6-38.5; p=0.0141). The pCR for Group C was 16.8% and Group D was 24.0%. It was also noted that in all groups, more individuals with hormone receptor-negative tumors achieved pCR with pertuzumab and trastuzumab than those individuals with hormone receptor-positive tumors. Six percent (25 of 417) of participants did not have surgery due to insufficient therapeutic response. The majority of these non-surgical candidates were from Group C. Most adverse events were grades 1-2, with the most frequently occurring events being alopecia, neutropenia, diarrhea, fatigue, rash and mucosal inflammation. The most common adverse event of grade 3 or higher was febrile neutropenia at 7-8% in Groups A, B and D. The combination of pertuzumab, trastuzumab and docetaxel significantly improved the pCR rate. Additional adjuvant trials to support the neoadjuvant approach were recommended.

The National Comprehensive Cancer Network® (NCCN®) clinical practice guidelines (CPG) (2017) for breast cancer were updated to include an off-label 2A recommendation for the use of pertuzumab in the adjuvant setting if a regimen containing pertuzumab was not used as neoadjuvant therapy, with support based on an extrapolation of evidence from treatment (overall survival of approximately 42 months compared to 38 months in the CLEOPATRA trial) in participants with metastatic disease and improvements in pathological complete response in the neoadjuvant setting (approximately 46% for pertuzumab+, trastuzumab + docetaxel compared to 29% trastuzumab + docetaxel). In addition, specialty consensus opinion recommends the use of pertuzumab in the adjuvant setting with the identified regimens and pertuzumab is limited to a maximum of 6 cycles based on the FDA labeled dosing recommendation in the neoadjuvant setting. There is an ongoing phase III trial evaluating pertuzumab as adjuvant therapy in combination with trastuzumab for HER2-positive breast cancer.

Von Minckwitz and colleagues (2017) reported findings from a prospective, double-blind, placebo-controlled trial that randomized individuals with node-positive (63%) or high-risk node-negative HER2-positive (36%), operable breast cancer to receive chemotherapy and 1 year of treatment of pertuzumab plus trastuzumab (maximum of 18 cycles every 3 weeks) (n=2400) or chemotherapy and 1 year of trastuzumab plus placebo (n=2405). Disease recurrence occurred in 7.1% (n=171) of participants in the pertuzumab group and 8.7% (n=210) participants in the placebo group (HR, 0.81; 95% CI, 0.66 to 1.00; p=0.045). Von Minckwitz and colleagues reported:

The estimates of the 3-year rates of invasive-disease-free survival were 94.1% in the pertuzumab group and 93.2% in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease-free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease-free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P=0.64).

In summary the authors conclude that “pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy. Diarrhea was more common with pertuzumab than with placebo”.

Metastatic breast cancer
In 2012, the FDA approved pertuzumab in combination with trastuzumab and docetaxel for individuals with HER2-positive metastatic breast cancer who have not previously received anti-HER2 therapy or chemotherapy treatment for the metastatic disease. The approval was based on the significantly improved progression-free survival (PFS) results from the phase III, double-blind, placebo-controlled Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) trial. A total of 808 participants with HER2-positive, metastatic breast cancer were enrolled into the study. Participants were eligible if they did not receive prior chemotherapy for the metastatic disease. One hormonal treatment prior to randomization was allowed. The median PFS was 18.5 months for those randomized to the group treated with pertuzumab + trastuzumab and docetaxel compared to a median PFS of 12.4 months in the control group treated with placebo plus trastuzumab and docetaxel. The median number of treatment cycles per participant was 15 (range 1-50) in the control group and 18 (range 1-56) in the pertuzumab cohort. For both groups, the median number of cycles with docetaxel was 8; (range 1-41) for the control group and (range 1-35) for the pertuzumab group. The control group had more frequent left ventricular systolic dysfunction (8.3%) compared to the treatment group combining trastuzumab and pertuzumab (4.4%) (Baselga, 2012; Pertuzumab Product Information, 2017).

After an additional year of follow-up, a second interim analysis of the data from the CLEOPATRA trial was performed. Swain (2013) reported a significant survival benefit for those treated with pertuzumab compared to the placebo group. The median overall survival (OS) for the pertuzumab group was not reached (95% confidence interval [CI], 42.4 months to not estimable [NE]) compared to 37.6 months (95% CI, 34.3-NE) for the placebo cohort. The number of deaths in the placebo group compared to the pertuzumab group was statistically significant (154 of 406 [38%] vs. 113 of 402 [28%]; hazard ratio [HR] 0.66, 95% CI, 0.52-0.84; p=0.0008). The median PFS was 12.4 months (95% CI, 10.4-13.5) for the placebo group and 18.7 months (16.2-21.6) for the pertuzumab group (HR 0.69, 95% CI, 0.58-0.81). Diarrhea, rash, pruritus and mucosal inflammation occurred with higher frequencies in the pertuzumab group compared to placebo. The rate of left-ventricular systolic dysfunction was not increased in the pertuzumab cohort.

The NCCN breast cancer CPG (2017) recommends the use of pertuzumab to treat metastatic HER2-positive breast cancer in specific situations. The CPG recommends with a category 1 level of evidence, pertuzumab plus trastuzumab in combination with a taxane docetaxel as a preferred option for first-line treatment of individuals with HER2-positive metastatic breast cancer. Pertuzumab plus trastuzumab in combination with paclitaxel is an NCCN category 2A recommendation. Additionally, NCCN recommends “for patients with disease progression after treatment with trastuzumab-based therapy without pertuzumab, a line of therapy containing both trastuzumab plus pertuzumab with or without a cytotoxic agent (such as vinorelbine or taxane) may be considered.” Also, specialty consensus opinion suggests that pertuzumab in combination with trastuzumab and docetaxel or paclitaxel may be used in a single line of therapy for metastatic disease.

The American Society of Clinical Oncology (ASCO) Clinical Practice Guideline for systemic therapy for treatment of advanced HER2+ breast cancer (Giordano, 2014) includes a strong recommendation: “Clinicians should recommend the combination of trastuzumab, pertuzumab, and a taxane for first-line treatment, unless the patient has a contraindication to taxanes.” In addition, the guideline notes “Use of paclitaxel with pertuzumab and trastuzumab was also reasonable, particularly for patients who might not be good candidates for docetaxel.”

HER2 overexpression
The key selection criterion for pertuzumab and trastuzumab is HER2 overexpression. In the pivotal breast cancer clinical trials, HER2 overexpression was determined by scores of 2+ or 3+ resulting from the IHC Clinical Trial Assay (CTA), which is utilized in research settings. Individuals with scores of 0 or 1+ were not included in the trials. Subsequently, the FDA has approved commercially available IHC tests to determine HER2 overexpression, which include Herceptest® (Dako Corp., Glostrup, Denmark) and Pathway™ (Ventana Medical Systems, Tucson, AZ). In addition, FDA approved tests which measure FISH of the HER2/neu protein include PharmDx™ (Dako Corp., Glostrup Denmark), Dako HER2 FISH PharmDx™ test kit (Dako Corp., Glostrup, Denmark), PathVysion™ (Abbott-Vysis Inc., Downers Grove, IL) and INFORM (Ventana Medical Systems, Tucson, AZ).

However, studies have shown that HER2 positivity may vary from laboratory to laboratory, and according to whether IHC or FISH methodology is used. In 2007, the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) developed joint guideline recommendations for HER2 testing in breast cancer and the guideline was updated in 2013 (Wolff 2007; 2013). The guideline was established to promote complete and standardized reporting of malignant pathology to “Improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer” (Wolff, 2013). The guideline recommends all individuals with newly diagnosed and recurrent invasive breast cancer should have tumors HER2 tested by laboratories that are accredited to perform HER2 testing. The updated guideline defines the results of HER2 testing as follows:

Positive HER2:

Equivocal HER2:

Negative HER2 if a single test (or both tests) performed show:

For individuals with equivocal results, the guidelines (Wolff, 2013) recommend additional testing with a reflex test (on the same specimen using the alternative test) or a new test (new specimen if available, using same or alternative test).

NCCN guidelines for breast cancer (2017) have incorporated the updated ASCO/CAP recommendations for HER2 status into the treatment algorithms for HER2 targeted therapy.

Other Uses

Multiple phase 2 clinical trials are currently evaluating the use of pertuzumab as a treatment for other solid tumors (for example, colorectal cancer, gastric cancer, neuroendocrine tumors, non-small cell lung cancer, and prostate cancer) and in combination with other drugs and targeted therapies. However, the data demonstrating safety and efficacy from these trials have not been published.

As a result of clinical trials demonstrating the effectiveness of pertuzumab with chemotherapy, additional clinical trials are studying the efficacy of adding pertuzumab to specific targeted biologic agents and/or with other chemotherapy agents. However, at this time, there is no evidence to support the safety and efficacy of combining pertuzumab with other biologic agents not discussed above.

Additionally, investigators continue to study the prevalence and role of anti-HER2 therapy in other malignancies. However, there have been no large randomized controlled trials to draw reasonable conclusions regarding the safety and efficacy of pertuzumab versus current standard therapies for malignancies other than breast cancers. NCCN guidelines for gastric cancer (2017) do not recommend the use of pertuzumab to treat gastric cancer.

Drug Schedules:
The Product Information Label (2017) for pertuzumab includes the following recommended doses and schedules:

Metastatic Breast Cancer:
Perjeta, trastuzumab, and docetaxel should be administered sequentially. Perjeta and trastuzumab can be given in any order. Docetaxel should be administered after Perjeta and trastuzumab. An observation period of 30 to 60 minutes is recommended after each Perjeta infusion and before commencement of any subsequent infusion of trastuzumab or docetaxel.

Neoadjuvant treatment of Breast Cancer:
Perjeta should be administered every 3 weeks for 3 to 6 cycles as part of one of the following treatment regimens for early breast cancer:

Following surgery, patients should continue to receive trastuzumab to complete 1 year of treatment. There is insufficient evidence to recommend continued use of Perjeta for greater than 6 cycles for early breast cancer. There is insufficient evidence to recommend concomitant administration of an anthracycline with Perjeta, and there are no safety data to support sequential use of doxorubicin with Perjeta.

Adverse Events and Warnings:
The Product Information Label (2017) for pertuzumab includes the following Black Box warnings:

Additional warnings and precautions from the label (2016) include left ventricular dysfunction and infusion-associated reactions/anaphylaxis. In the metastatic and neoadjuvant settings, the most common adverse events (occurring >30%) reported with pertuzumab in combination with trastuzumab and docetaxel were diarrhea, alopecia, nausea, and neutropenia.

Definitions

Adjuvant therapy: Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biological therapy.

Disease-free survival (DFS): The interval between a complete disappearance of the cancer (complete response) and the time of relapse.

Hormonal therapy: Treatment that adds, blocks, or removes hormones. Agents that slow or stop the growth of certain cancers, synthetic hormones or other drugs may be given to block the body’s natural hormones.

Line of therapy:

Metastatic: The spread of cancer from one part of the body to another. A metastatic tumor contains cells that are like those in the original (primary) tumor and have spread.

Monoclonal antibody: A protein developed in the laboratory that can locate and bind to specific substances in the body and on the surface of cancer cells.

Neoadjuvant therapy: Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given. Examples of neoadjuvant therapy include chemotherapy, radiation therapy, and hormone therapy. It is a type of induction therapy.

Off-label: Utilization of a United States Food and Drug Administration (FDA) approved drug for uses other than those listed in the FDA approved label.

Pathological complete response (pCR) in the breast: The absence of invasive neoplastic cells at microscopic examination of the primary tumor at surgery.

Primary treatment: The first treatment given for a disease. It is often part of a standard set of treatments, such as surgery followed by chemotherapy and radiation. Also called first-line therapy, induction therapy, and primary therapy.

Targeted biologic agent: A newer type of drug developed specifically to target genetic changes in cells that cause cancer. It works differently than standard chemotherapy drugs, often with different side effects.

References

Peer Reviewed Publications:

  1. Andersson M, Lidbrink E, Bjerre K, et al. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol. 2011; 29(3):264-271.
  2. Baselga J, Cortés J, Im SA, et al. Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. J Clin Oncol. 2014; 32(33):3753-3761.
  3. Baselga J, Cortes J, Kim SB, et al.; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012; 366(2):109-119.
  4. Baselga J, Gelmon KA, Verma S, et al. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol. 2010; 28(7):1138-1144.
  5. Cortés J, Baselga, Im YH, et al. Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Ann Oncol. 2013; 24(10):2630-2635.
  6. Cortés J, Fumoleau P, Bianchi GV, et al. Pertuzumab monotherapy after trastuzumab-based treatment and subsequent reintroduction of trastuzumab: activity and tolerability in patients with advanced human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2012; 30(14):1594-1600.
  7. Garg A, Li J, Clark E, Knott A, et al. Exposure-response analysis of pertuzumab in HER2-positive metastatic breast cancer: absence of effect on QTc prolongation and other ECG parameters. Cancer Chemother Pharmacol. 2013; 72(5):1133-1141.
  8. Gianni L, Pienkowski T, Im YH, et al. 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. 2012; 13(1):25-32.
  9. Kang YK, Rha SY, Tassone P, et al. A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. Br J Cancer. 2014; 111(4):660-666.
  10. Kümler I, Tuxen MK, Nielsen DL. A systematic review of dual targeting in HER2-positive breast cancer. Cancer Treat Rev. 2014; 40(2):259-270.
  11. Schneeweiss A, Chia S, Hickish T, et al. 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 (TYRPHAENA). Ann Oncol. 2013; 24(9):2278-2284.
  12. Swain SM, Baselga J, Kim SB, et al.; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015; 372(8):724-734.
  13. Swain SM, Baselga J, Miles D, et al. Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase III study CLEOPATRA. Ann Oncol. 2014; 25(6):1116-1121.
  14. Swain SM, Ewer MS, Cortes J, et al. Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in CLEOPATRA: a randomized, double-blind, placebo-controlled phase III study. Oncologist. 2013; 18(3):257-264.
  15. Swain SM, Kim SB, Cortes J, et al. 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. 2013; 14(6):461-471.
  16. Von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017; 377(2):122-131.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Cancer Society. Cancer facts & figures 2017. Atlanta: American Cancer Society; 2017.
  2. Balduzzi S, Mantarro S, Guarneri V, et al. Trastuzumab-containing regimens for metastatic breast cancer. Cochrane Database Syst Rev. 2014;(6):CD006242.
  3. Giordano SH, Temin S, Kirshner JJ, et al.; American Society of Clinical Oncology. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014; 32(19):2078-2099.
  4. Haldar K, Gaitskell K, Bryant A, et al. Epidermal growth factor receptor blockers for the treatment of ovarian cancer. Cochrane Database of Syst Rev. 2011;(10):CD007927.
  5. Hoffmann-La Roche. 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 (APHINITY). Last updated July 18, 2017. NLM Identifier: NCT01358877. Available at: https://clinicaltrials.gov/ct2/show/NCT01358877. Accessed on September 21, 2017.
  6. National Comprehensive Cancer Network®. NCCN Drugs & Biologic Compendium® (electronic version). For additional information visit the NCCN website: http://www.nccn.org. Accessed on September 5, 2017.
  7. NCCN Clinical Practice Guidelines in Oncology™. © 2017 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org. Accessed on September 21, 2017.
    1. Breast Cancer (V.2.2017). Revised April 6, 2017.
    2. Gastric Cancer (V.4.2017). Revised September 21, 2017.
  8. Perjeta [Product Information], San Francisco, CA. Genentech. May 1, 2017. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=17f85d17-ab71-4f5b-9fe3-0b8c822f69ff. Accessed on September 26, 2017.
  9. Pertuzumab. In: DrugPoints System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated September 1, 2017. Available at: http://www.micromedexsolutions.com. Accessed on September 21, 2017.
  10. Pertuzumab Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised May 30, 2013. Accessed on September 21, 2017.
  11. Wolff A, Hammond MEH, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013; 31(31):3997-4013.
  12. Wolff A, Hammond MEH, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007; 25(1):118-145.
Websites for Additional Information
  1. American Cancer Society. About breast cancer. Revised June 1, 2016. Available at: https://www.cancer.org/cancer/breast-cancer/about.html. Accessed on September 21, 2017.
  2. National Cancer Institute. Breast Cancer Treatment PDQ®. Modified: August 23, 2017. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/breast/healthprofessional. Accessed on September 21, 2017.
Index

HER2; Her2-neu
Monoclonal antibody

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

New

11/02/2017

Medical Policy & Technology Assessment Committee (MPTAC) review.

New

11/01/2017

Hematology/Oncology Subcommittee review. Initial Document development. Moved content for DRUG.00052 Pertuzumab (Perjeta®) to new clinical utilization management guideline document with the same title.