Dual-target combination, composing music for "raw" Domestic trastuzumab combined with pertuzumab neoadjuvant therapy to win the "breast defense battle" for young breast cancer patients

HER2-positive breast cancer is highly aggressive, has a high recurrence rate, and has a poor
prognosis.
The dual-target regimen of trastuzumab combined with pertuzumab is the treatment of choice for HER2-positive breast cancer and improves survival
in patients with HER2-positive breast cancer.
As the first trastuzumab biosimilar marketed in China, the efficacy is equivalent to that of the original trastuzumab, and has been approved for all indications of the original trastuzumab, which can also be used
in combination with pertuzumab.
Through a young HER2-positive breast cancer case, this article introduces the clinical benefits and safety of
Hanqu You* combined with pertuzumab neoadjuvant in the treatment of HER2-positive breast cancer.

Brief history of history

The patient is a 38-year-old woman who is not menopausal
.

Medical history: the patient accidentally found a right breast mass before 2 months, and found right axillary lymphadenopathy due to axillary pain 1 month ago, no fever night sweats, chest tightness and breath holding, inverted nipples, desquamation and erosion of nipples, redness and swelling of the skin, no nipple discharge
, and no treatment.
A mass of about 2.
5 cm * 3 cm in size can be palpated above the outside of the right breast, which is hard, poorly bounded, has poor mobility, and the right axilla can reach the toughness with tender lymph nodes
.
For further diagnosis and treatment, 2021-10-14 was admitted to the hospital
.

Anamnesis: Normal and healthy
.

Auxiliary examination: Breast MRI of the patient 2021-10-14 showed that the right breast central gland area and the right breast outer upper quadrant area showed an irregular cluster shadow with a cross-section of about 71mm*34mm, BI-RADS class 6; Multiple lymphadenopathy in the right armpit
.

Pathological examination: (right breast mass biopsy) invasive carcinoma, histological grade III
.
Immunohistochemistry results: ER (Allred score 3+2-5 points, 30%+), PR (Allred score 5+2-7 points, 70%+), HER2 (3+), Ki67 (about 40%+ in dense areas), P63(-), Calponin(-)
.

Initial diagnosis: invasive carcinoma of the right breast, grade III

After treatment

Neoadjuvant therapy: patients received a six-cycle "docetaxel + carboplatin + trastuzumab + pertuzumab" (TCbHP) regimen from 2021-10 to 2022-3
.

Management of adverse effects: left ventricular ejection fraction was 61%, which was not significantly lower than before neoadjuvant therapy (62%)
.

Efficacy evaluation: The patient's 2022-03-09 MRI showed that irregular stripes of shadow could be seen in the right breast, the range was significantly smaller than before (2021.
10.
14), and multiple small lymph nodes
were seen in the right armpit.
Efficacy was assessed as partial response (PR).

Preoperative diagnosis: after neoadjuvant therapy for invasive right breast carcinoma, BI-RADS class
6.

Surgery: The patient underwent stage I breast reconstruction of latissimus dorsi flap under general anesthesia + modified radical mastectomy for right breast cancer + inferior mammary wrinkle wall plasty
on 2022-03-11.

Postoperative pathology: (right subpapillary tissue) intraductal carcinoma with calcification (non-frozen section tissue), the diameter of the microscopic range is about 0.
55mm
.
No cancer was found on the "outside" of the marker (lateral and inferior expansion tissue), and the surrounding breast tissue showed adenopathy changes with ductal dilation; After chemotherapy, the specimen was removed, the size of the mass was 1.
0cm*1.
0cm, and no cancer metastasis was found in the lymph nodes: (0/21) (right axillary tissue) 0/19 (lateral group) fat fiber connective tissue (tongue fat) fat fiber connective tissue (right subclavian lymph node) 0/2
.
Assessment of response to neoadjuvant chemotherapy (Miller-Payne grade): grade 4 (significantly more than 90% reduction in infiltrating cancer cells).

Postoperative pathological stage: ypT1N0M0

Postoperative adjuvant therapy: patients require postoperative radiotherapy and further targeted and endocrine therapy
.

Case summary

For the neoadjuvant therapy strategy for HER2-positive breast cancer, the 2022 edition of the Chinese Society of Clinical Oncology (CSCO) Breast Cancer Diagnosis and Treatment Guidelines takes TCbHP regimen treatment as a level I recommendation
.
In this case, the patient received a total of 6 cycles of TCbHP regimen, and the local lesions of the breast retreated significantly and the effect was remarkable, and there were no adverse reactions
related to targeted drugs during neoadjuvant therapy.
This patient is a young breast cancer patient with a strong willingness to conserve breast, and it is the significant effect of TCbHP regimen during neoadjuvant therapy that lays a safe and solid foundation for the patient's later breast-conserving surgery, and can remove the tumor, "escorting"
long-term benefits.

The mechanism of action of trastuzumab is complementary in the treatment of HER2 breast cancer and has synergistic antitumor effects, in which trastuzumab acts on the extracellular domain IV.
of HER2 receptors, blocks the formation of dimers, and blocks signal transduction from extracellular, while pertuzumab acts on HER2 receptor extracellular domain II.
, and the dual-target therapy of trastuzumab combined with pertuzumab has become the level I recommendation
for neoadjuvant therapy for HER2-positive breast cancer.

According to the results of phase III clinical studies of Hanquyou, the efficacy is equivalent to that of the original trastuzumab, and the safety and immunogenicity are similar ^[1].

Moreover, trastuzumab biosimilars have been recommended by a number of authoritative diagnosis and treatment guidelines at home and abroad, which point out that biosimilars have the same efficacy and safety as the original product, and can be used clinically as an alternative
.

Expert reviews

The 2022 edition of the CSCO Guidelines for the Diagnosis and Treatment of Breast Cancer points out that preoperative neoadjuvant drug treatment can be selected if one of the following conditions is met: (1) a large mass (>5cm); (2) axillary lymph node metastasis; (3) HER2 positive; (4) triple negative; (5) Those who
are willing to conserve breast, but the ratio of tumor size to breast volume is large and difficult to conserve breast.
According to the molecular typing and clinical stage of this patient, the TCbHP regimen can be treated with neoadjuvant therapy
according to the guidelines.

Previous NeoSphere studies have demonstrated that pertuzumab + trastuzumab combined with docetaxel can increase the rate of pathological complete response (pCR) in patients with HER2-positive breast cancer ^[2].

This conclusion was also confirmed by the first PEONY study based on Asian populations, which showed that the dual-target neoadjuvant regimen of trastuzumab + pertuzumab combined with docetaxel could improve the efficacy of neoadjuvant therapy for HER2-positive breast cancer, further promoting the use of dual-target neoadjuvant regimen in Asian HER2-positive breast cancer patients ^[3].

In the Kristine study, the TCbHP regimen had an extremely low event-free survival (EFS) event rate in the neoadjuvant phase, demonstrating the efficacy and safety
of TCbHP regimen in neoadjuvant therapy.
TRAIN-2 studies have shown that TCbHP regimens achieve the same pCR rates and significantly lower toxicities such as neutropenia compared with anthracycline-containing regimens ^[4-5].

Therefore, the combination of trastuzumab + pertuzumab with chemotherapy has become the standard regimen
for HER2-positive breast neoadjuvant therapy.

As the first domestic monoclonal antibody drug in China and Europe, on August 12, 2020, Hanquyou was officially approved for marketing by the State Food and Drug Administration of China, becoming the first domestic trastuzumab; Prior to this, on July 27, 2020, Hanquyou had been approved
by the European Commission (EC).
Since the launch of Hanquyou, it has accumulated many real-world use bases and experiences, and the production of trastuzumab in China not only meets the high-quality medication needs of patients, but also provides more patients with affordable high-quality biological drugs
.

*In this article, Hanqu You is trastuzumab developed and produced by Henlius

References:

[1].
Xu B, Zhang Q, Sun T, et al.
Efficacy, Safety, and Immunogenicity of HLX02 Compared with Reference Trastuzumab in Patients with Recurrent or Metastatic HER2-Positive Breast Cancer: A Randomized Phase III Equivalence Trial.
BioDrugs.
2021 May; 35(3):337-350.

[2].
Gianni L, Pienkowski T, Im YH, et al.
5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer ( NeoSphere): a multicentre, open-label, phase 2 randomised trial.
Lancet Oncol.
2016 Jun; 17(6):791-800.

[3].
Shao Z, Pang D, Yang H, et al.
Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial.
JAMA Oncol.
2020 Mar 1; 6(3):e193692.

[4].
Hurvitz SA, Martin M, Symmans WF, et al.
Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial.
Lancet Oncol.
2018 Jan; 19(1):115-126.

[5].
van Ramshorst MS, van der Voort A, van Werkhoven ED, et al.
Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial.
Lancet Oncol.
2018 Dec; 19(12):1630-1640.