The US Food and Drug Administration (FDA) approved pertuzumab (Perjeta; Genentech) for use in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. This approval was granted on June 8, 2012. For more information about the FDA approval, see http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm307592.htm.
When a patient with human epidermal growth factor receptor 2 (HER2)-positive breast cancer is given a personalized treatment plan, she discovers that she is one of the more than 20% of women with the HER2 gene that causes the cancer cells to grow faster, have a higher tendency to metastasize, and recur in the future.1,2 To combat this poorer prognostic breast cancer, the patient commits to a year of trastuzumab treatment, with the vision of continuing the journey as a cancer-free survivor.
JS is a 54-year-old female who was diagnosed with T2N0M0 breast cancer 2 years ago. She is one of the 15% of patients with breast cancer who relapsed after adjuvant trastuzumab treatment.2 After completing her trastuzumab treatment and being diligent in her follow-up visits, JS presented with a persistent cough that she had attributed to an earlier cold. After all other cold symptoms had abated, she followed up with her medical oncologist, who ordered a PET scan, which showed hypermetabolic mediastinal and hilar nodes with sternal bone metastasis.
The oncologist explained the plan for a combined anti-HER2/neu therapy or dual HER2 blockade. JS recalled the mechanism of trastuzumab as a drug that attaches to the HER2 receptors on breast cancer cells and blocks the growth signals from the body as well as directs the immune system to destroy cancer cells onto which the extra HER2 receptors are attached.3 JS was further educated on the concept of dimerization, or pairing together, of HER2 and HER3, thus causing intracellular pathways to develop.4 It was explained that pertuzumab blocks HER2 and HER3 from creating a union that would enable further cancer growth. Trastuzumab used along with pertuzumab blocks any “foot action” between HER2 and HER3 and does not allow them to “hold hands”—further inhibiting interaction between the receptors. To reinforce this information with a visual learning experience, JS watched an educational video about dimerization on Genentech’s pertuzumab website.4 Because the video is designed for healthcare professionals, certain terms needed to be explained to JS, but she found the visuals to be helpful. In addition, the pertuzumab website designed for patients and caregivers provides information about a pertuzumab support line with nurse availability as well as access to healthcare coverage information and patient assistance programs.5
After JS completed her restaging and prechemotherapy testing, she was started on docetaxel, pertuzumab, and trastuzumab, the National Comprehensive Cancer Network’s preferred first-line agent for HER2-positive recurrent or metastatic breast disease.6 She has since completed 6 cycles, and her primary side effects have been fatigue, diarrhea, alopecia, and a skin rash; all appeared after the first treatment. None of these effects were grade 3 or 4 adverse events as described in the National Cancer Institute’s Common Terminology Criteria for Adverse Events v4.0 (CTCAE).7 The CTCAE is a descriptive tool accepted throughout the oncology community as a standard classification for adverse effects in oncology.
While the side effects have been tolerable enough to allow her to continue working, they have limited her participation in many of her extracurricular activities. Her fatigue was managed by the use of evidence-based interventions provided by the Oncology Nursing Society PEP (Putting Evidence Into Practice) resources.8 JS had set a priority to continue to work, both for her self-esteem and for her emotional needs, so this was set as a base for her energy conservation and activity management. She did allow herself to attend a weekly church service and continue small outdoor walks with her husband for exercise and relaxation. Her blood counts (HgB) have been stable, and her sleep quality is best after the effect of her steroid treatment declines after chemotherapy.
Diarrhea was a concern with the struggle to stay hydrated, and her worst episode has been a grade 2. JS balances the use of loperamide, diet intake, and other strategies with what she calls “intentional hydration,” or focusing on her fluid intake. The diarrhea usually abates within days after treatment, and she has adjusted her work schedule to accommodate this side effect.
Alopecia was an expected effect, and she coped well with it last time by having different wigs, scarves, and accessories to enhance her appearance. She remembered the tips she received from the Personal Care Products Council Foundation’s Look Good Feel Better program.9 A local program site can be found by going to the Look Good Feel Better website at http://lookgoodfeelbetter.org/programs.
The skin on her dorsal hands, forearms, and abdomen showed a fine macular, reticular rash that presented without itching after her initial treatment. It subsided with the use of diphenhydramine cream, and adding pre- and posttreatment steroid tapering was also helpful.
JS is aware of the other common side effects with pertuzumab, such as neutropenia, nausea, neuropathy, and cardiac concerns. She continues her heart function monitoring as determined by her oncologist, and she understands the need to communicate any concerns to her healthcare team at the clinic. She is elated that her most recent PET scan results showed improvement and feels like her current treatment allows her quality time with a balance of family and work.
As new therapies are developed, nurses learn about new cancer management options along with their patients. With the application of these therapies to the metastatic setting, the nurse takes her knowledge bank and proactively teaches and looks for possible side effects, acknowledging that each individual patient may have different risks for various effects. For example, patients treated with previous anthracyclines or radiation to the chest may be at higher risk for left ventricular dysfunction; the diabetic patient may be a challenge with peripheral neuropathy; and heavily prior-treated patients for metastatic breast cancer may struggle with fatigue, neutropenia, or nausea and vomiting. Also, each patient with metastatic breast cancer brings an individual emotional response based on her judgment of how she tolerated side effects from the previous treatment and the meaning that is attached to the recurrent cancer.
It will be interesting to watch the future implications and development of metastatic treatment. Will this involve the movement of initial metastatic drugs to the adjuvant setting? Will we see more targeted therapies with less systemic side effects? Hopefully, the evidence-based practice to address side effects will continue to develop. With the personalized assessment each patient receives prior to starting treatment, and the use of all available tools and resources, the journey for metastatic patients is well supported to enable the best-quality experience with their chronic disease.
1. Phillips C. Treatment options for HER2-positive breast cancer expand and evolve. NCI Cancer Bulletin. 2012;9(20):2. http://www.cancer.gov/ncicancerbulletin/101612/page2. Published October 16, 2012. Accessed March 27, 2013.
2. Nahta R, Esteva F. HER2 therapy: molecular mechanisms of trastuzumab resistance. Breast Cancer Res. 2006;8(6):215.
3. Genentech Inc. Proposed mechanism of action: Herceptin MOA. Herceptin (trastuzumab) Healthcare Professionals Web site. http://www.herceptin.com/hcp/treatment/moa. Accessed March 27, 2013.
4. Genentech Inc. Proposed mechanism of action: inhibit dimerization for more comprehensive HER2 blockade. PERJETA (pertuzumab) Healthcare Professionals Web site. http://www.perjeta.com/hcp/moa. Accessed March 27, 2013.
5. PERJETA (pertuzumab) Patient & Caregivers Web site. http://www.perjeta.com/patient/index. Accessed March 27, 2013.
6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 2.2013. http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Updated March 11, 2013. Accessed April 25, 2013.
7. National Cancer Institute, National Institutes of Health. Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Bethesda, MD: National Institutes of Health; 2009. NIH publication 09-5410. http://evs.nci.nih.gov/ftp1/CTCAE/About.html. Revised June 14, 2010. Accessed April 25, 2013.
8. Oncology Nursing Society. ONS PEP®−Putting Evidence Into Practice. http://www.ons.org/Research/PEP. Accessed April 25, 2013.
9. The Personal Care Products Council Foundation. Look Good Feel Better Web site. http://lookgoodfeelbetter.org/. Accessed April 25, 2013.