Pertuzumab Therapy - Perjeta
Pertuzumab, sold as Perjeta, is a second HER2 antibody given with trastuzumab and chemotherapy for HER2-positive breast cancer, before surgery, after surgery in node-positive disease, and as first treatment when the cancer has spread. This page covers how dual HER2 blockade works, who gains and who does not, the key trials, the combined injection with trastuzumab, diarrhea and other side effects, and how patients from abroad arrange treatment in Istanbul.
About This Department
Trastuzumab blocks HER2 from one side. Pertuzumab blocks it from another, so the growth signal has nowhere left to go. Given together, they added more than sixteen months to median survival in spread breast cancer.
Pertuzumab, sold under the brand name Perjeta, is a second antibody against HER2 that is always given together with trastuzumab and chemotherapy, never alone. Where trastuzumab stops the receptor signaling on its own, pertuzumab stops it pairing with its neighbors, and the two together close the pathway more completely than either. In HER2-positive breast cancer that had spread, adding pertuzumab raised median survival from 40.8 to 57.1 months and survival at eight years from 23 to 37 percent (Swain and colleagues, Lancet Oncology, 2020). Before surgery, it raised the rate of complete disappearance of cancer in the breast from 29.0 to 45.8 percent (Gianni and colleagues, Lancet Oncology, 2012). After surgery, its benefit concentrated in patients with cancer in the lymph nodes (von Minckwitz and colleagues, New England Journal of Medicine, 2017). This page explains how pertuzumab works, which patients gain from it and which do not, its use before surgery, after surgery and in spread disease, the combined injection, the side effects, and how patients from abroad arrange treatment at Biruni Hospital in Istanbul.
What pertuzumab is
HER2 rarely acts alone. To send its growth signal it pairs with another receptor of the same family, most powerfully with one called HER3, and the pair fires more strongly than either would. Trastuzumab binds one part of HER2 and blocks the signal it sends on its own. Pertuzumab binds a different part, the arm HER2 uses to reach its partners, and prevents the pairing. With both antibodies on the receptor, the cancer cell loses the signal from every direction the drugs can reach.
HER2-targeted therapy has changed the natural history of HER2-positive metastatic breast cancer, with the dual blockade of pertuzumab and trastuzumab, with docetaxel, demonstrating an eight-year landmark overall survival rate of 37 percent (Swain and colleagues, 2020).
Who gains from it
HER2-positive breast cancer, by the tests described on the trastuzumab page. Within that group the benefit depends on how much risk the cancer carries, which is measured by the size of the tumor, the state of the lymph nodes, the hormone receptors and, when treatment starts before surgery, by how much of the cancer the first cycles manage to clear.
Does every patient with HER2-positive breast cancer need pertuzumab?
| Situation | Pertuzumab | Reason |
|---|---|---|
| Tumor over 2 cm or positive nodes, treatment before surgery | Yes, with trastuzumab and chemotherapy | Higher rate of complete response |
| Positive nodes, treatment after surgery | Yes, to complete a year | Lower risk of recurrence in trials |
| Small tumor, clear nodes | No, trastuzumab alone | No benefit shown |
| Cancer left in the breast after treatment before surgery | No, switched to trastuzumab emtansine | The carrier drug works better here |
| Spread disease, first treatment | Yes, with trastuzumab and a taxane | Longer survival |
| HER2-positive stomach cancer | No | A trial in stomach cancer showed no survival gain |
Before surgery
- Four to six cycles, every three weeks. Pertuzumab, trastuzumab and chemotherapy, with a taxane at the center and a platinum or an anthracycline in some regimens.
- Surgery, three to six weeks later. Lumpectomy or mastectomy and a sentinel node biopsy, planned from the response seen on imaging.
- The pathology report. Complete response or cancer left behind, which decides the treatment for the rest of the year.
A complete pathological response means the pathologist found no invasive cancer in the breast or the lymph nodes removed at surgery. Patients who reach it have a lower risk of recurrence than those who do not.
| Treatment before surgery | Patients | No invasive cancer in the breast |
|---|---|---|
| Trastuzumab and docetaxel | 107 | 29.0 percent |
| Pertuzumab, trastuzumab and docetaxel | 107 | 45.8 percent |
| Pertuzumab and trastuzumab, no chemotherapy | 107 | 16.8 percent |
| Pertuzumab and docetaxel | 96 | 24.0 percent |
After surgery
How much does pertuzumab add after surgery?
| Group | With pertuzumab | With placebo |
|---|---|---|
| All patients | 94.1 percent free of invasive disease | 93.2 percent |
| Positive lymph nodes | 92.0 percent | 90.2 percent |
| Clear lymph nodes | 97.5 percent | 98.4 percent |
| Severe diarrhea during chemotherapy | 9.8 percent | 3.7 percent |
The numbers look small because the outlook with trastuzumab alone is already good, and a drug that improves an excellent result can only ever add a little in absolute terms, however much it lowers the relative risk. A reduction from 9.8 to 8.0 recurrences per hundred node-positive women means that one or two women in every hundred treated are spared a recurrence at three years, and the gap widens with time.
Breast cancer that has spread
The trial that made pertuzumab a standard, and the one with the longest follow-up of any HER2 combination in spread disease.
Median overall survival was 57.1 months in the pertuzumab group and 40.8 months in the placebo group. Eight-year survival was 37 percent against 23 percent, after a median follow-up of more than eight years (Swain and colleagues, 2020).
Infusion or injection
Two drips, one after the other.
One injection for both
Should I choose the infusion or the injection?
Availability of the combined injection varies by country, and the file review confirms which form can be given here and at home.
Side effects
Mostly the gut. Rarely more.
- Diarrhea, the side effect that belongs to pertuzumab. Mild in most patients, severe in about one in ten during chemotherapy, and much less once chemotherapy stops.
- Rash, dry skin and nail changes, mild and treated with creams.
- Infusion reactions with the first dose, chills or fever, prevented by a slower rate and managed at the chair.
- The chemotherapy side effects, low blood counts, hair loss and neuropathy, which belong to the taxane rather than the antibodies.
| When | What to do | When to call |
|---|---|---|
| First episode | Loperamide after each loose stool, fluids with salt | If more than four a day despite loperamide |
| During chemotherapy cycles | Keep loperamide at home, avoid lactose and fat for a few days | Fever, blood, dizziness or inability to keep fluids down |
| After chemotherapy ends | Diarrhea eases in most, treatment continues | If it returns and persists beyond a week |
The heart
Less of a worry than patients expect.
Heart failure, cardiac death and cardiac dysfunction were infrequent in both treatment groups in the trial after surgery, and one new case of heart failure appeared in eight years of follow-up in the trial of spread disease (von Minckwitz and colleagues, 2017. Swain and colleagues, 2020).
Treatment for patients from abroad
How the year is arranged
Questions worth settling before the first dose
Four of them.
Whether the lymph nodes carry cancer, since the answer decides whether pertuzumab after surgery is justified at all, and a patient with a small tumor and clear nodes should hear that trastuzumab alone serves her equally well. Whether treatment will start before surgery, which is where pertuzumab does the most visible good. Which form will be used, since the combined injection turns a morning in the day unit into a few minutes and makes it far easier to continue treatment at home or while working. And how the diarrhea will be handled, because it is the side effect that most often interrupts the course, and a patient who leaves the first visit with loperamide in her bag, a written rule for when to call, and a number that answers at night has done more to protect her treatment than any other single step. A patient who arrives with a plan made elsewhere and asks these four questions will learn quickly whether the plan fits her cancer.
Good plans survive them. Weak ones do not.
Cost
One figure per cycle, after the file review.
| Item | Usually included | Priced separately |
|---|---|---|
| The antibodies | Pertuzumab and trastuzumab for the cycle, as infusions or the combined injection | Chemotherapy, trastuzumab emtansine |
| The visit | Consultation, blood tests, administration, observation | Admission for a side effect |
| Tests and imaging | Routine blood tests | Heart scans, staging scans, pathology review |
Pertuzumab costs more than trastuzumab and has no biosimilar in wide use, so the drug makes up most of the figure. Compare quotes for the same form and the same inclusions, and ask whether the heart scans every three months are part of it.
References
- Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA). End-of-study results from a double-blind, randomized, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519-530.
- 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.
- 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 randomized multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32.
- Tan AR, Im SA, Mattar A, et al. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa). A randomized, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021;22(1):85-97.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Özcan YILDIZ, Medical Oncology.
Medically reviewed by
Prof. Dr. Özcan YILDIZ
Medical Oncology
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