*For medical professionals only
Experts interpret the key points of the update of the "CSCO Breast Cancer Diagnosis and Treatment Guidelines 2024".
The 2024 National Breast Cancer Conference and the Chinese Society of Clinical Oncology Breast Cancer (CSCO BC) Annual Meeting was held in Beijing from April 12 to 13. During the conference, the CSCO Guidelines for the Diagnosis and Treatment of Breast Cancer 2024 were officially released [1]. The formulation of CSCO guidelines fully considers regional development differences, the availability of drugs and diagnosis and treatment, and the social value of cancer treatment. On the basis of following the principles of evidence-based medicine and combining with expert consensus, scientific diagnosis and treatment opinions were put forward for various clinical problems, and corresponding recommendation levels were formulated according to the accessibility and potency ratio of products. This guideline not only reflects the scientific and rigorous attitude, but also takes into account the clinical practice of the mainland, which is of great value and significance for guiding the clinical diagnosis and treatment of breast cancer in China. The update of the CSCO breast cancer diagnosis and treatment guidelines in 2024 will undoubtedly provide clearer and stronger support and guidance for the clinical practice of breast cancer in mainland China. The Medical Oncology Channel specially invited Professor Zhang Qingyuan from the Affiliated Cancer Hospital of Harbin Medical University and Professor Zhang Jian from the Affiliated Cancer Hospital of Fudan University to sort out and interpret the key points of this guideline update for readers.
Summary of the key points of the CSCO Guidelines for the Diagnosis and Treatment of Breast Cancer 2024
HER2-positive advanced breast cancer: "Trastuzumab (T-DXd)" replaces "Trastuzumab (T-DM1)" as the only ADC recommended for Level I after trastuzumab treatment failure (1A).
Triple negative advanced breast cancer: the original rescue therapy recommendation form was adjusted to two forms, rescue chemotherapy and rescue immunotherapy, and the immunization combination regimen was recommended separately.
HR-positive advanced breast cancer: "AKT inhibitor (AKTi) + endocrine" has been added as a grade III treatment recommendation for patients who have failed CDK4/6 inhibitor (CDK4/6i).
New chapter on advanced breast cancer with low HER2 expression:
- For advanced breast cancer with HR-positive/HER2 low expression, "T-DXd" is the preferred level II recommendation for CDK4/6i-experienced patients (1A).
- For HR-negative/HER2-low advanced breast cancer, ADC therapy should be preferred after failure of first-line therapy, and "gosatuzumab" or "T-DXd" should be selected.
Prof. Qingyuan Zhang: T-DXd is the only ADC drug recommended for the second-line treatment of HER2-positive advanced breast cancer
Figure 1. Rescue treatment options for HER2-positive advanced breast cancer
- In patients who are sensitive to trastuzumab therapy, trastuzumab in combination with taxanes (THP), trastuzumab in combination with pyrotinib, and taxanes (TH+pyrotinib) remain Level I recommendations, and the evidence category has been adjusted to 1A.
- In patients who failed trastuzumab, T-DXd was the only ADC recommended for Level I (1A), while T-DM1 was adjusted from a Level I recommendation to a Level II recommendation.
- In patients who have failed TKI therapy, T-DXd remains a Level II recommendation, but the evidence category has been raised to 1A.
- New subcutaneous formulations of trastuzumab and pertuzumab.
- Note 3: Add (7) "After failure of T-DXd therapy, consideration may be given to the use of previously beneficial anti-HER2-targeted therapy or unused drugs of the same type, and the feasibility of topical therapy should also be considered to take into account quality of life." ”
The Level I recommendation for T-DXd as a second-line treatment for HER2-positive advanced breast cancer is based on the breakthrough benefits of the DESTINY-Breast03 study. As of July 25, 2022, the median PFS assessed by BICR in the T-DXd arm was 28.8 months, which was 4.2 times higher than the 6.8 months in the T-DM1 arm. Although the median OS was not reached in both groups, there was a statistically significant difference between the T-DXd group and the T-DM1 group (HR=0.64, P=0.0037). In addition, the BICR-confirmed ORR was as high as 78.5 percent in the T-DXd group compared with 35 percent in the T-DM1 group, with a CR rate of 21.1 percent and a median DoR of 36.6 months in the T-DXd group[2].
With such excellent PFS and OS data, T-DXd has become a new benchmark for the second-line treatment of HER2-positive advanced breast cancer. International authoritative guidelines, such as NCCN, ESMO, ASCO, and ABC7, have unanimously recommended T-DXd as the preferred second-line treatment for HER2-positive advanced breast cancer [3-6]. The 2022 CSCO guidelines for the diagnosis and treatment of breast cancer also follow the trend and include T-DXd in the drug recommendation for the second-line treatment of HER2-positive advanced breast cancer [7]. With the official approval of T-DXd for marketing in China on February 21, 2023, its drug accessibility has been significantly improved. Therefore, in the CSCO Guidelines for the Diagnosis and Treatment of Breast Cancer 2024, T-DXd replaces T-DM1 as the only ADC drug recommended for the second-line treatment of HER2-positive advanced breast cancer. This major update not only strengthens the position of T-DXd as the second-line standard of care for HER2-positive advanced breast cancer, but also further promotes the progress and development of breast cancer treatment.
Prof. Jian Zhang: HER2 low expression is listed as a separate chapter, and T-DXd is recommended as a treatment for HER2 low expression advanced breast cancer, regardless of HR status
Figure 2. Rescue treatment options for advanced breast cancer with low HER2 expression
- For HR-positive/HER2-low advanced breast cancer: Endocrine + CDK4/6i remains a class I recommendation (1A) if CDK4/6i is untreated, T-DXd is the preferred tier II recommendation (1A) if CDK4/6i is treated, chemotherapy and other endocrine therapies are also considered optional tier II (2A), and gosatuzumab is classified as a tier III recommendation (2A).
- For HR-negative/HER2-low advanced breast cancer: first-line treatment is recommended for triple-negative breast cancer, with chemotherapy or chemotherapy combined with immunotherapy, and after first-line therapy failure, ADC drugs should be preferred, with gosatuzumab or T-DXd as the first choice.
Low HER2 expression (IHC 1+ or IHC2+/ISH-) accounts for approximately 45% to 55% of all breast cancers and tends to be higher in HR-positive patients. In view of the differences in the survival prognosis of low HER2 expression and the efficacy of multiple therapies compared with zero HER2 expression, the identification of HER2 low expression populations should be paid attention to in clinical practice [1]. For the first time, the CSCO Guidelines for the Diagnosis and Treatment of Breast Cancer 2024 have added a new chapter on "Rescue Therapy for Advanced Breast Cancer with Low HER2 Expression", aiming to raise the attention of clinicians to this patient group and provide practical management recommendations for this group of patients.
The shaping and establishment of HER2 low expression therapeutic subtypes is based on the results of the breakthrough study of DESTINY-Breast04. The study included patients with HER2-low expression advanced breast cancer who had received 1-2 lines of chemotherapy before, and more than 80% of them were HR-positive and were identified as endocrine-refractory, and more than 70% of them had received CDK4/6i therapy. The results showed that in HR-positive/HER2-low expression populations, T-DXd significantly extended PFS (10.1 versus 5.4 months, HR=0.51, P<0.001) and OS (23.9 versus 17.5 months, HR=0.64, P=0.003) compared with chemotherapy in HR-negative/HER2-low expression populations, while PFS (8.5 versus 2.9 months, HR=0.46) and OS (18.2 versus 8.3 months, HR=) were significantly longer than chemotherapy in HR-negative/HER2-low expression populations0.48) was consistent with the overall population and the HR-positive population [8].
The remarkable results of the new ADC drug T-DXd in the DESTINY-Breast04 study have completely changed the traditional dichotomy of breast cancer treatment. This breakthrough not only means that HER2-low breast cancer has officially entered a new era of targeted therapy, but also brings unprecedented new hope for treatment to a wider range of patients. On July 12, 2023, T-DXd was successfully approved for the indication of HER2-low expression advanced breast cancer in China, which is not only a recognition of the excellent efficacy of T-DXd, but also a profound change in the field of breast cancer treatment in China. The 2024 CSCO Breast Cancer Guidelines elaborate on HER2 low expression as a separate chapter, further highlighting the role of T-DXd in the treatment of HER2-low advanced breast cancer. This change is not only an affirmation of the clinical value of T-DXd, but also a strong impetus for the development of the entire field of breast cancer treatment.
With the rapid development of medicine, especially the continuous development and iteration of anti-HER2 drugs, the survival outcome of HER2-positive advanced breast cancer is undergoing profound changes. In particular, T-DXd, a novel ADC drug, reinvents the second-line standard of care for HER2-positive advanced breast cancer with its outstanding performance in the DESTINY-Breast03 study. T-DXd has also shown amazing therapeutic effects in patients with low HER2 expression in the DESTINY-Breast04 study, successfully broadening the boundaries of the beneficiary group of breast cancer anti-HER2 therapy and bringing new changes to the field of breast cancer treatment.
The update of the CSCO Guidelines for the Diagnosis and Treatment of Breast Cancer 2024 is the best testimony to these changes. This guideline is closely integrated with the actual situation in China and actively absorbs the cutting-edge international research results to ensure the timeliness and pertinence of treatment recommendations. It acts as a bright beacon to guide breast cancer patients on the path to higher quality and more efficient treatment. In this wave of change, we have witnessed the power and hope of medicine, and also felt the infinite possibilities of science and technology and innovation. Let's look forward to the emergence of more revolutionary drugs such as T-DXd in the field of breast cancer treatment in the future, bringing hope and light to more breast cancer patients.
Expert Profile
Prof. Qingyuan Zhang
- Chief physician, second-level professor, doctoral supervisor
- Director of Heilongjiang Provincial Institute of Cancer Prevention and Control
- Vice President of the Affiliated Cancer Hospital of Harbin Medical University
- Leader of the National Key Specialty of Oncology
- Selected for the National Millions of Talents Project
- Young and middle-aged experts with outstanding contributions to the country
- Vice Chairman of the Breast Cancer Committee of the Chinese Anti-Cancer Association
- Vice Chairman of the Breast Cancer Expert Committee of the Chinese Society of Clinical Oncology
- Chairman of the Breast Cancer Professional Committee of Heilongjiang Anti-Cancer Association
Expert Profile
Prof. Jian Zhang
- Chief physician of the Department of Medical Oncology, Ph.D. supervisor, and medical director of the Phase I Clinical Research Ward of Fudan University Cancer Hospital
- Director of the Clinical Research Center of Fujian Hospital, Fudan University Cancer Hospital/Executive Deputy Director of the Department of Medical Oncology
- Chairman of the Cancer Prevention and Clinical Research Committee of the Chinese Geriatric Health Care Association
- Chairman of the Yangtze River Academic Belt Breast Alliance YBCSG
- Chairman-elect of the Tumor Drug Clinical Research Committee of Shanghai Anti-Cancer Association
- Member of the Standing Committee of the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association
- Deputy Convener of the Youth Committee of the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association
- Vice Chairman of the Youth Committee of the Breast Professional Committee of the Chinese Research Hospital Association
- Vice Chairman of the Youth Committee of the National Youth Committee for Monitoring the Clinical Application of Anti-tumor Drugs
- Vice Chairman of the Oncology and Cardiology Committee of Shanghai Anti-Cancer Association
- Member of the Standing Committee of CSCO Tumor Support and Rehabilitation Therapy Expert Committee
- Member of the Standing Committee of the Cancer Rehabilitation Professional Committee of the Chinese Association of Rehabilitation Medicine
- Member of the Standing Committee of the CSCO Youth Expert Committee
- Member of the CSCO Breast Cancer Expert Committee
- Member of the Cancer Clinical Research Management Committee of the Chinese Anti-Cancer Association
- Winner of Shanghai "Medical Garden Rising Star" Outstanding Young Talent
- The first batch of part-time reviewers of chemical drugs clinical trial in the CDE of the State Food and Drug Administration
- He won the 2023 Top Ten Medical Pioneer Experts and the 2023 "People's Good Doctor" Outstanding Contribution Award
- Associate Editor-in-Chief of Diseases&Research and Associate Editor-in-Chief of the Electronic Journal of Comprehensive Cancer Treatment of Human Health
- 72 SCI papers (Lancet Oncol, Ann Oncol, Nat Commun, Clin Cancer Res, J Hematol Oncol, etc.)
Bibliography:
[1] CSCO Guidelines for the Diagnosis and Treatment of Breast Cancer 2024.
[2] Cortés J, Kim SB, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. N Engl J Med. 2022 Mar 24; 386(12):1143-1154.
[3] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Breast Cancer. Version 1.2024 — January 25, 2024.
[4] Curigliano G, Castelo-Branco L, Gennari A, et al. ESMO Metastatic Breast Cancer Living Guidelines, v1.1 May 2023.
[5] Giordano SH, Franzoi MAB, Temin S, et al. Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: ASCO Guideline Update. J Clin Oncol. 2022 Aug 10; 40(23):2612-2635.
[6] International Consensus on ABC7 Advanced Breast Cancer.
[7] CSCO Guidelines for Breast Cancer Diagnosis and Treatment 2022.
[8] Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7; 387(1):9-20.
* This article is only for the purpose of providing scientific information to medical professionals and does not represent the views of this platform