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    Home > Active Ingredient News > Antitumor Therapy > 2021 CSCO BC | Prof. Yingying Xu: Best of BCC 2021 Neoadjuvant Therapy Hot Interpretation

    2021 CSCO BC | Prof. Yingying Xu: Best of BCC 2021 Neoadjuvant Therapy Hot Interpretation

    • Last Update: 2021-04-23
    • Source: Internet
    • Author: User
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    Neoadjuvant therapy is an important part of comprehensive treatment of breast cancer.

    In the 17th St.
    Gallen International Breast Cancer Conference (SG-BCC 2021), neoadjuvant therapy has become another hot topic.

    In this regard, at the 2021 National Breast Cancer Conference and the Chinese Society of Clinical Oncology Breast Cancer (CSCO BC) Annual Conference, Professor Xu Yingying of Breast Surgery Department of the First Affiliated Hospital of China Medical University explained the hot issues of neoadjuvant therapy at the SG-BCC conference.

    Expert profile Prof.
    Yingying Xu Deputy Director of Breast Surgery, First Affiliated Hospital of China Medical University Deputy Chairman, Youth Committee, Chinese Medical Association Oncology Branch, Secretary of Breast Oncology Group, Chinese Medical Association Oncology Branch, Chinese Anti-Cancer Association Breast Cancer Professional Committee, Youth Committee The chairman's new adjuvant therapy concept is upgraded.
    Neoadjuvant therapy can be targeted to the whole body or locally.

    In terms of targeted localization, neoadjuvant therapy can reduce surgery and breast preservation, and for patients with better local control, such as N0-N1 patients, it can protect the axilla.

    From the perspective of obtaining drug susceptibility information in the body, researchers can use neoadjuvant therapy for early efficacy detection and strategy adjustment, and make decisions on adjuvant therapy based on neoadjuvant therapy.

    In addition, neoadjuvant therapy can also provide time for patient genetic testing and provide a platform for drug development.

    The first stage: the implementation of neoadjuvant therapy for the population of neoadjuvant therapy is mainly divided into three stages and two nodes.

    In the first phase, the researcher should think about which types of patients should be treated with neoadjuvant therapy.

    Regarding the question "Do all patients who need adjuvant therapy need neoadjuvant therapy?", 60% of the experts in the consensus vote of the St Gallen Conference are opposed to it.
    This may be due to concerns about overtreatment of some patients, such as low-risk patients.
    Patients with HER-2 positive small tumors.In the APT study, paclitaxel combined with trastuzumab can achieve 93.
    3% of 7-year disease-free survival (DFS).

    Patients with T1c and below stage accounted for more than 90% of the total enrolled patients, and the proportion of T2 patients was less than 10%.

    Therefore, many experts have reservations about the update of the American Society of Clinical Oncology (ASCO) guidelines recommending that patients with T1c and above HER-2 positive breast cancer receive neoadjuvant therapy.

    The recommendation in the ASCO guidelines is based on many clinical trials that include T1c patients, but from the perspective of clinical practice, the selection of options and the evaluation of efficacy are not very practical.

    Therefore, Professor Xu believes that patients with HER-2 positive breast cancer (cT≥2 or cN≥1) are the preferred population for neoadjuvant therapy.

    When selecting neoadjuvant populations for early breast cancer, researchers should consider the following questions: (1) For patients, is neoadjuvant therapy a clinical trial or clinical practice? (2) Can neoadjuvant therapy change the patient's local or systemic treatment strategy? From the perspective of clinical practice, the purpose of treatment is the basis for the selection of neoadjuvant treatment populations in clinical practice.

    The second stage: clinical implementation In the clinical implementation stage, the researcher should think about what kind of plan is the standard plan of neoadjuvant treatment.

    Although the pathological complete remission (pCR) rate of neoadjuvant therapy is encouraging, most experts believe that the determination of the "standard" regimen of neoadjuvant therapy should be based on long-term disease-free survival (EFS) or overall survival (OS) endpoints .

    An adjuvant treatment plan with evidence of survival must be a standard neoadjuvant treatment plan, but "standard" does not mean "excellent".

    Therefore, Professor Xu said that he looks forward to the emergence of better solutions that can increase pCR and improve survival.

    Can a plan that can increase pCR without compromising patient survival be used as a neoadjuvant treatment plan? Professor Xu believes that from the point of view of the treatment of partial staging to ensure the axillary fall, the plan to increase pCR is valuable.

    For different molecular subtypes, the significance of neoadjuvant therapy is also different.

    Triple negative breast cancer (TNBC) patients are a group of patients with strong heterogeneity, poor prognosis, and lack of driver genes.

    Therefore, researchers are thinking about how to use the neoadjuvant platform to expand the chemotherapy regimen based on paclitaxel + anthracycline.

    Regarding the question of whether "paclitaxel+anthracycline+platinum" can be used as a regular recommendation, 60% of the experts in the consensus vote of the St Gallen conference are opposed.

    This is because in previous clinical studies on paclitaxel+anthracycline+platinum regimens, only the Geparsict study showed that this regimen improved DFS, and other studies only showed an increase in pCR, so this regimen should not become the standard treatment.

    However, Chinese guidelines and consensus indicate that neoadjuvant chemotherapy for young TNBC patients, especially those with BRCA gene mutations, may prefer paclitaxel-based drugs combined with platinum-based drugs (TP).

    With the publication of the IMpassion031 research results, many people have high hopes for immunotherapy.

    However, most experts are opposed to the question of whether immune checkpoint inhibitors (ICI) are added to the neoadjuvant treatment of TNBC patients.

    This is because the results of ICI in neoadjuvant therapy studies are inconsistent, and programmed death ligand-1 (PD-L1) has not been found to be an effective biomarker for immune checkpoint inhibitors.

    Therefore, researchers should consider the dominant population of neoadjuvant immunotherapy and its best compatibility plan.

    For the neoadjuvant treatment of patients with HER-2 positive breast cancer, researchers should think about how to optimize the treatment plan.

    Taking anthracycline selection as an example, for patients with positive lymph nodes, overseas experts tend to add anthracyclines to neoadjuvant therapy; for patients with negative lymph nodes, most overseas experts believe that it is not necessary to add anthracyclines to neoadjuvant therapy.

     Figure 1.
    Voting results of neoadjuvant therapy for patients with HER-2 positive breast cancer.
    In the "NCCN Guidelines for Invasive Breast Cancer 2021", anthracyclines are no longer one of the adjuvant and neoadjuvant treatments for HER-2 positive breast cancer Class recommendation. Does this mean that the era of full exemption for anthracyclines is coming? Professor Xu held a disagreement and said: “For low-risk or sensitive patients, we should think about the downgrading treatment of dual-target combined with or without chemotherapy; for high-risk patients, we should think about the combination of anthracyclines and “yew”.
    Class + Trastuzumab + Pertuzumab" regimen (THP) or "Yaxane + Carboplatin + Trastuzumab + Pertuzumab" regimen (TCbHP); for high-risk HER-2 positive The choice of anthracyclines for neoadjuvant treatment of breast cancer patients is still controversial.

    "For low-risk or sensitive patients, researchers should consider dual-target or dual-target + single chemotherapy regimens; for triple-positive breast cancer patients, researchers should Consider the plan of dual target + endocrine therapy.

    In addition, researchers believe that neoadjuvant endocrine therapy has increased in importance in ER-positive and HER-2 negative breast cancer.

    As we all know, endocrine therapy is of great significance for hormone receptor positive and HER-2 negative breast cancer, but neoadjuvant endocrine therapy has not yet become a standard treatment.
    This is due to the choice of the population, the choice of regimen, the length of treatment, and the criteria for evaluating efficacy.
    Lack of uniform standards.

    The application of multi-gene detection tools allows some patients to avoid chemotherapy in adjuvant therapy, assists in the screening of patients for neoadjuvant research, and enables patients with medium and low scores to obtain better curative effects and higher breast-conserving rates from neoadjuvant endocrine therapy .

    Therefore, more than 70% of experts believe that genomic analysis of needle biopsy can be used to select ER-positive and HER-2 positive breast cancer patients for neoadjuvant endocrine therapy and chemotherapy; more than 90% of experts believe that for breast cancer patients with low genomic risk, chemotherapy Not better than endocrine therapy.

    In terms of efficacy evaluation indicators, Ki67 has shown its ability to predict prognosis in IMPACT and POETIC studies.

    For patients who are not sensitive to neoadjuvant endocrine therapy, the ADAPT study organically combines Ki67 with genetic testing technology.

    For genetically-at-risk patients, if the patient can make Ki67<10% within 3-4 weeks and receive complete endocrine therapy, the 5-year invasive disease-free survival (iDFS) rate can reach 93%.

     Figure 2.
    The third stage of ADAPT research design: postoperative treatment strategy conversion.
    At present, overseas experts are facing the confusion of how to convert postoperative treatment strategies.

    For patients with TNBC or HER-2 positive breast cancer, pCR is a well-defined endpoint.

    However, there are no good indicators for patients with ER positive or HER-2 negative.

    For patients with ER-positive breast cancer, most experts use anatomical analysis and tumor burden as one of the indicators.
    For example, patients with more than 4 lymph nodes or tumors greater than 5 cm should receive adjuvant chemotherapy.

    But this confusion is not easy to appear in China.

    This is because most patients receiving neoadjuvant endocrine therapy have the characteristics of old age and strong hormone receptor positive, so it is difficult for subsequent treatment to be converted into chemotherapy.

    The follow-up treatment plan for HER-2 positive breast cancer patients who achieve pCR is still a difficult problem to be solved.

    According to the consensus of European and American experts, there is a strong correlation between the initial lymph node status and subsequent administration.
    Taking lymph node-negative patients as an example, a single-target plan can be selected in the follow-up.

    For patients who have not reached pCR, most experts believe that T-DM1 should be used for adjuvant intensive treatment, even if the tumor is less than 5mm, the patient should also receive T-DM1 treatment.

    However, this consensus is inconsistent with the views of Chinese experts.

    Chinese experts believe that for patients who have reached pCR after neoadjuvant therapy, postoperative adjuvant therapy should continue the original targeted therapy.

    Based on the accessibility of T-DM1 and existing medical insurance policies.

    Economic factors, toxic and side effects and many other factors, for patients who have good curative effects but have not yet reached pCR, Chinese experts are more inclined to choose dual-target treatment options.

    Based on the CREATE-X study, capecitabine became the adjuvant enhancement standard for triple-negative breast cancer patients who did not meet the pCR.

    However, due to the strong heterogeneity of triple-negative breast cancer, researchers should conduct intensive treatment based on the patient's biomarkers.

    Related research is currently underway, such as the enhancement of ICI.

    Summary Neoadjuvant therapy is constantly improving under the existing framework, but it is still not perfect.

    Researchers should screen the population more accurately and give corresponding treatment plans.

    In the selection of the optimization plan, the researcher must take into account the local and global, short-term and long-term, curative effects and toxicity.

    In addition, early evaluation and program adjustments should also receive more attention.

    For patients with residual tumor lesions after surgery, under the guidance of biomarkers, a non-cross-resistance regimen can be selected for intensive treatment.

    In the 17th St Gallen Conference, the researchers proposed that the prognosis of pCR has a strong correlation with the initial anatomical analysis.

    Professor Xu believes that this may be due to the greater heterogeneity of locally advanced breast cancer patients and higher subclinical metastases, and subsequent pCR evaluation may be underestimated.
    As a result, patients with advanced breast cancer may reach pCR, but their prognosis is not as good as that of early patients.

    For such patients, researchers can use detection methods such as CTC or ctDNA to provide patients with better treatment strategies.

    In addition, the MDT team should participate in neoadjuvant treatment to make the process more standardized and precise.

    Professor Xu finally stated that neoadjuvant therapy is a bridge to individualized therapy, and in this process, standardized operations and strategies tailored to local conditions can promote the co-prosperity of theory and practice.

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