Roche's Innovative Breast Cancer Drug Perjeta Receives New Indication Approval in China for First-Line Treatment of HER2-Positive Metastatic Breast Cancer

Roche Pharma China announced today that the National Medical Products Administration (NMPA) of China has officially approved Pertuzumab (Perjeta®) in combination with Trastuzumab (Herceptin®) and docetaxel as a first-line standard treatment regimen for patients with HER2-positive metastatic breast cancer who have not previously received anti-HER2 therapy or chemotherapy. This approval marks a step toward aligning China’s treatment options for HER2-positive advanced breast cancer with international standards, offering prolonged survival benefits to patients and facilitating the chronic disease management model for breast cancer diagnosis and treatment, thereby making it possible to transform advanced breast cancer from a “terminal illness” into a manageable condition. The dual-targeted combination of pertuzumab and trastuzumab plus docetaxel is the internationally recognized standard first-line treatment for HER2-positive advanced breast cancer[1]. The approval of Perjeta® for this first-line indication in advanced breast cancer in China is not only significant for domestic patients but will also further promote the standardization of diagnosis and treatment for advanced breast cancer in China.

Survival Rate for Patients with Advanced Breast Cancer Is Only 20%; Dual-Target Therapy Will Reshape Treatment Outcomes in Advanced Disease

Breast cancer is the most common malignant tumor among Chinese women, ranking first in incidence among female malignancies. HER2-positive breast cancer accounts for approximately 20%–30% of cases [2]. Due to its high degree of malignancy, rapid disease progression, propensity for lymph node metastasis, short remission duration following chemotherapy, and relative resistance to endocrine therapy, it poses significant challenges to clinical management, resulting in an overall low quality of life for patients.

Among the annual new cases of breast cancer in China, approximately 3%–10% of women present with distant metastasis at diagnosis. Among patients with early-stage disease, 30%–40% will progress to advanced breast cancer, with a 5-year survival rate of only 20% and an overall median survival time of just 2–3 years [2]. The approval of Perjeta® for first-line treatment of advanced breast cancer will bring longer survival benefits to patients with HER2-positive advanced breast cancer.

The approval of the first-line treatment indication for Perjeta® in HER2-positive advanced breast cancer is primarily based on the results from two studies: the CLEOPATRA clinical trial with up to 8 years of follow-up, and the PUFFIN study conducted in the Chinese population. The CLEOPATRA study demonstrated that pertuzumab plus trastuzumab combined with docetaxel extended progression-free survival (PFS) by 51% to 18.7 months, and overall survival (OS) by 40%, extending survival to nearly 5 years [3]. With extended follow-up, at a median follow-up of 8 years (maximum follow-up of 10 years), 37% of patients in the pertuzumab plus trastuzumab and docetaxel group achieved 8-year survival, significantly higher than the 23% observed in the trastuzumab-only group. The PUFFIN study, a bridge study to CLEOPATRA, enrolled 243 Chinese patients with HER2-positive advanced breast cancer from 15 clinical centers across China. Its results were consistent with those of the previous CLEOPATRA study. The trend in PFS benefit observed in the PUFFIN study was consistent with global data [4].

From the CLEOPATRA to PUFFIN clinical trials, we can observe that pertuzumab plus trastuzumab combined with docetaxel further prolongs progression-free survival (PFS) compared to trastuzumab monotherapy, in both non-Chinese and Chinese populations. Professor Xu Binghe from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, who led the PUFFIN study, stated: “The PUFFIN study demonstrated a high consistency between the efficacy of dual HER2-targeted therapy (pertuzumab plus trastuzumab) in Chinese patients with HER2-positive advanced breast cancer and the international CLEOPATRA study. It confirmed that the dual-target regimen of pertuzumab combined with trastuzumab offers similar safety and survival benefits in Chinese patients, providing robust evidence-based medical support for the confident use of this regimen in China. We believe that with longer follow-up, the overall survival (OS) data from the PUFFIN study will reveal impressive results for the Chinese population, further driving changes in the diagnosis and treatment landscape for HER2-positive advanced breast cancer in our country.”

Dual-Targeted Therapy with Trastuzumab and Pertuzumab Promotes Chronic Disease Management, Making It Possible for Advanced Breast Cancer to Cease Being a “Terminal Illness”

How Can the Pertuzumab and Trastuzumab Dual-Target Regimen Effectively Promote the Chronic Disease Management of Advanced Breast Cancer? Professor Jiang Zefei, Vice Chairman of the Chinese Society of Clinical Oncology (CSCO), explained, “The CLEOPATRA study released an 8-year follow-up result this year, showing that the 8-year overall survival rate for patients approached 40%. In the field of breast cancer treatment, it is rare to have studies with such a long observation period, given that the patients are in the advanced stage. The results from the CLEOPATRA study clearly demonstrate that the vast majority of patients can achieve long-term survival benefits after receiving dual-target therapy with pertuzumab and trastuzumab.”

In addition, the combination of Perjeta® (pertuzumab) + Herceptin® (trastuzumab) + chemotherapy can also provide comprehensive benefits for patients with HER2-positive advanced breast cancer in first-line treatment. Its efficacy is not influenced by prior (neo)adjuvant trastuzumab therapy, age, or hormone receptor status. Significant benefits are consistently observed in HER2-positive advanced breast cancer patients with brain metastases, visceral metastases, or bone metastases [5], offering hope to all patients with advanced disease and making it possible to transform advanced breast cancer from a “terminal illness” into a manageable condition.

For patients with advanced breast cancer, experts urge that, on one hand, early diagnosis and detection must be strengthened to reduce the likelihood of initial presentation at an advanced stage. On the other hand, for patients who, due to various reasons, still progress to advanced disease, attention should be paid to timely intervention in accordance with the Guidelines, so as to prolong survival and improve quality of life.

In the “Healthy China 2030” Planning Outline released by the Central Committee of the Communist Party of China and the State Council on July 15, 2019, it was stated that “by 2022 and 2030, the overall five-year survival rate for cancer should be no less than 43.3% and 46.6%, respectively.” Currently, the five-year survival rate for patients with early-stage breast cancer in China has reached 83.2%[6], achieving its transformation into a “chronic disease.” However, to improve the overall survival rate for breast cancer, it is particularly critical to address the current shortfall where the survival rate for patients with advanced breast cancer stands at only 20%. Therefore, the approval of the first-line treatment indication for advanced disease using trastuzumab dual-targeted therapy responds to this need, helping to increase the survival rate of patients with advanced breast cancer in China and contributing to the building of a Healthy China.

Successive Indications Approved: Roche Provides Comprehensive Care Management for Breast Cancer Patients

Zhou Hong, President of Roche Pharma China, stated, “Although Pertuzumab (Perjeta®) entered the Chinese market later than it did in Europe and the United States, all three of its indications were approved in China within a single year, achieving synchronization with Western markets. This world-class approval speed demonstrates the Chinese government’s determination to accelerate the introduction of innovative medicines through reform and continuously improve the health of the Chinese people. Roche will continue to uphold its philosophy of ‘acting in the best interests of patients first.’ Building on our commitment to innovative research and development, we will bring more innovative products to market to benefit a greater number of breast cancer patients in China.”

In December 2018, the first indication for Perjeta® was approved in China for adjuvant treatment in combination with trastuzumab and chemotherapy in patients with HER2-positive early breast cancer at high risk of recurrence, significantly reducing the risk of recurrence in this population and marking the official entry of anti-HER2 therapy in China into the era of dual-targeted treatment.

In August 2019, the China National Medical Products Administration approved the use of pertuzumab in combination with trastuzumab and chemotherapy for the neoadjuvant treatment of patients with HER2-positive locally advanced, inflammatory, or early-stage breast cancer (tumor diameter >2 cm or lymph node-positive), as part of the overall treatment regimen for early breast cancer, thereby providing a novel preoperative treatment option for patients with HER2-positive early breast cancer.

Perjeta®’s approval for the first-line treatment indication in HER2-positive advanced breast cancer marks its third approved indication in China. The combination of pertuzumab, trastuzumab, and chemotherapy has established comprehensive HER2 inhibition management for patients across the entire treatment continuum, from the initial neoadjuvant phase through postoperative adjuvant therapy to advanced-stage disease, thereby positively promoting standardized, full-process diagnosis and treatment of breast cancer in China.

The recent national medical insurance negotiations have concluded. Herceptin® in the dual-target therapy regimen has successfully renewed its inclusion in the National Medical Insurance list and has added a new indication for neoadjuvant treatment. Meanwhile, Perjeta® has been included for the first time in the "National Basic Medical Insurance, Work-Related Injury Insurance, and Maternity Insurance Drug Catalog" for neoadjuvant treatment of patients with HER2-positive locally advanced, inflammatory, or early-stage breast cancer, as well as for adjuvant treatment of patients with HER2-positive early-stage breast cancer at high risk of recurrence. It is believed that under the support of national medical insurance policies, patient access to medications will be significantly improved, enabling an increasing number of breast cancer patients to receive standardized dual-target therapy and benefit from it.

[1] Swain SM，Baselga J，Kim SB，et al.Pertuzumab，trastuzumba，and docetaxel in HER2-positive metastatic breast cancer [J].N Engl J Med, 2015, 372(8): 724-734.

[2] Chinese Expert Consensus on Clinical Diagnosis and Treatment of Advanced Breast Cancer (2018 Edition), Chinese Journal of Oncology, Vol. 40, No. 9, September 2018

[3] Swain SM, et al. ASCO.2019. abstract 1020

[4] Binghe Xu, et al. 2019 ASCO. Abstract 1026

[5] Russillo M A, et al. In Vivo. 2018 Jul-Aug; 32(4): 839-842.

[6] Binghe Xu, et al. 2019 ASCO. Abstract 1026