Professor Li Junjie: The results of the monarchE study on Asian populations are announced, and the intensive endocrine therapy for early breast cancer has added a new "edge"!

*Only for medical professionals to read and reference the value of adjuvant treatment of early breast cancer with inhibitors highlights, and listen to Professor Li Junjie's in-depth interpretation! 2021 European Society of Medical Oncology Breast Cancer Annual Meeting (ESMO-BC) has been held online from May 5 to May 8, 2021.

The application value of CDK4/6 inhibitors in the adjuvant intensive endocrine therapy of hormone receptor positive (HR+)/HER2-early breast cancer has always attracted clinical attention.
The results of the subgroup analysis of the monarchE study for Asian populations in this meeting are "astounding" "Appearance" again adds strong evidence for the intensive endocrine therapy strategy for HR+/HER2-early breast cancer.

 "Luminal breast cancer accounts for a very high proportion of all breast cancers, and its large prevalence base and high disease burden are practical problems faced in clinical practice.

Therefore, the research progress in the field of luminal breast cancer, especially the improvement of treatment , Clinicians and patients are very concerned; and due to the disease characteristics of luminal breast cancer, how to achieve early and long-term benefits is an urgent problem to be solved.

"Professor Li Junjie, Department of Breast Surgery, Fudan University Cancer Hospital, said.

The "medical community" specially invited Professor Li Junjie to give an in-depth interpretation of the relevant research progress and clinical practice experience of CDK4/6 inhibitors at this ESMO-BC conference.

 Challenges and opportunities coexist: The adjuvant endocrine therapy model is undergoing innovation.
Professor Li Junjie’s wonderful video About 20% of HR+/HER2-early breast cancer patients will experience disease recurrence within the first 10 years, and certain high-risk clinical and/or pathological features may increase recurrence risks of.

Therefore, adjuvant endocrine therapy is an important part of the treatment of early breast cancer.

In recent years, with the development of new drugs and the emergence of new treatments, some changes may have taken place in their treatments, but in general, endocrine therapy is more of an "addition", that is, intensive endocrine therapy.
There are mainly two Directions: Add ovarian function inhibitors (OFS) or extend the time of adjuvant endocrine therapy for premenopausal patients with intermediate and high risk.

 “Early adjuvant treatment of premenopausal patients adopts intensive treatment with OFS to control the level of hormones in the patient’s body to a lower range.

But in essence, this treatment model is only a'simulation' of the natural state of postmenopausal patients, thus Achieve a similar prognosis, but it is not the most perfect choice.

" Professor Li Junjie said.

A series of issues such as the choice of adjuvant therapy for premenopausal patients, the application of OFS therapy and the choice of combined endocrine therapy drugs, and the choice of adjuvant endocrine therapy for postmenopausal patients and the course of treatment are still controversial.

 Although some previous studies have shown that in breast cancer patients with a high risk of recurrence with positive lymph nodes, the traditional 5-year adjuvant endocrine therapy will continue to be given for the follow-up 5-year intensive endocrine therapy.
Although there is a trend to reduce the risk of recurrence, large-scale clinical trials are still needed.
authenticating.

 Professor Li Junjie added: “If the patient’s tumor burden is high, how can it be ensured that the patient will not recur within 5 years so that he can receive the follow-up endocrine prolongation treatment? Therefore, as the risk of recurrence becomes higher and higher, blindly prolonging the endocrine treatment course is not Solve all problems.
The
 above two contradictions still exist.
How can patients with high tumor burden at the first diagnosis and high risk of recurrence in the first 5 years undergo intensive endocrine therapy? CDK4/6 inhibitors have emerged as the times require, due to the first-line and second-line HR+ breast cancer The remarkable curative effect of treatment has become one of the standard treatments for advanced HR+ breast cancer.

Researchers have further explored the value of CDK4/6 inhibitors in the adjuvant treatment stage.
Therefore, CDK4/6 inhibitors are used in adjuvant therapy.
The evidence of evidence-based medicine has always been a hot spot and focus of clinical attention. "The dawn of dawn: the only positive result of adjuvant therapy in the monarchE study, Professor Junjie Li Wonderful video Different CDK4/6 inhibitors have explored the value of adjuvant endocrine therapy for high-risk HR+/HER2- early breast cancer, but the results and benefits of the study are somewhat different Different.
The
monarchE study is currently the only clinical study with positive results: In September 2020, the interim analysis results of the monarchE study were announced simultaneously in the 2020 ESMO conference and the JCO (Journal of Clinical Oncology) [1]; 2020 San Antonio Breast Cancer Conference ( SABCS) announced the final analysis results of the primary endpoint of the monarchE study for invasive disease-free survival (iDFS)[2].

 From the final efficacy analysis results of the study, abesiride combined with standard adjuvant endocrine therapy is used for high-risk (lymph node positive> 4 or 1-3 lymph nodes are positive and accompanied by any high-risk factors including masses greater than 5cm, G3 or/and T3, and high Ki67) HR+/HER2-early breast cancer compared with standard adjuvant endocrine therapy significantly improved patients' iDFS by 28.
7 % Risk of recurrence (HR=0.
713; 95% CI 0.
583-0.
871; P=0.
00009) [2].

 Figure 1 The results of iDFS of the monarchE study at the 2020 SABCS conference "When a clinical trial is announced and the primary research endpoint is reached, the established event is observed After a few hours, it can be considered that the test can be used for final efficacy analysis.

Therefore, although the monarchE study was followed up for less than two years, we were able to confirm that the monarchE study was a complete trial with positive results.

 So far, the monarchE study has published two data.
In comparison, the hazard ratio (HR) value of the trial was 0.
747 in the interim analysis and 0.
713 in the final efficacy analysis.
The absolute benefits were very stable and similar.

Therefore, this part of patients who meet the entry criteria of the monarchE study can significantly improve the prognosis in the adjuvant phase combined with abesiride, and the evidence of intensive adjuvant therapy for early high-risk breast patients is also abundant.

"Professor Li Junjie said.

 Asian "exclusive" data: the benefits are consistent, the safety is better or better.
Professor Li Junjie's wonderful video At this ESMO-BC conference, monarchE researched Asian population iDFS, survival without remote recurrence (DRFS) and adverse reactions and other related data were announced one after another , The therapeutic value of Abexicil in the Asian population has once again highlighted [3].

 From the point of view of efficacy data, a total of 75 iDFS events were observed in Asian populations (33 cases in the Abexiride combined with standard adjuvant endocrine therapy group and 42 cases in the standard adjuvant endocrine therapy group); compared with the control group, abexiride combined with endocrine therapy Treatment significantly improved iDFS and reduced the risk of invasive disease progression by 22.
3% (HR=0.
777; 95% CI, 0.
493-1.
227) (Figure 2).

Figure 2 The results of iDFS in Asian populations studied by monarchE.
The 2-year iDFS rates of the abesiride combined with adjuvant endocrine therapy group and the endocrine therapy group alone were 93.
2% and 90.
1%, respectively, and the absolute benefit of the 2-year iDFS rate was 3.
1%; the 2-year DRFS rate was respectively They were 94.
4% and 91.
7% (HR=0.
758; 95%CI, 0.
455-1.
264), and the absolute benefit of the 2-year DRFS rate was 2.
7% (Figure 3).

 Figure 3 DRFS results of Asian population in the monarchE study Professor Li Junjie said: “Race and region have always been used as established subgroups of global clinical trials for efficacy analysis.
In the monarchE study, Asian populations accounted for about 20% of the overall population.
From the efficacy results From the above point of view, the benefits of the Asian population are exactly the same as the overall population trend, which means that the value of Abesiride in the adjuvant treatment of the Asian population has been confirmed.

As a clinician, I will pay more attention to the tolerance of the Asian population to the treatment.
We also saw a very interesting result in the ESMO-BC data release: the incidence of a series of toxic side effects such as dose adjustment and drug discontinuation due to adverse reactions is lower, that is, Asian populations may be better tolerated. From the perspective of diarrhea, the most important adverse reaction of abexiride, the majority of Asian populations have degree I/II, and the incidence of drug suspension, drug reduction, and interruption of drug administration due to diarrhea is higher than that of non-Asian populations.
Significantly lower; although neutropenia and leukopenia lead to a higher incidence of dose maintenance and/or reduction, toxicity is still manageable.

Such safety data also gives Chinese clinicians more confidence to use them safely and effectively in clinical practice.

The results of the Chinese population of the monarchE study will also be announced at the annual meeting of the American Society of Clinical Oncology (ASCO).

”Scroll up and down to see more Figures 4 5 6 The results of the monarchE study on the safety of Asian populations are gradually advancing: China’s early high-risk breast cancer better survival is just around the corner How should it be applied to benefit more patients? Professor Li Junjie expressed relevant insights: “Abexicil has high-level evidence-based medicine evidence to confirm its efficacy and benefits, but it has not yet been recommended by the guidelines and the indications have not been obtained.
However, there is a'contradiction' in clinical application.

Fortunately, the country is also committed to accelerating the approval of new drugs, so we also hope that Abexicil will be approved as an adjuvant therapy for breast cancer as soon as possible for wider application.

Personally, for early breast cancer patients who meet the monarchE study entry criteria, especially those with high acceptance of cutting-edge research progress, I will fully inform the relevant evidence-based medicine evidence.

Patients will decide whether to choose drugs based on comprehensive considerations such as drug availability and economic conditions.

"The MonarchE study has confirmed the value of abesiride in the adjuvant treatment of early-stage high-risk breast cancer patients, but there are still many directions worth exploring in the future for enhanced adjuvant endocrine therapy.

Professor Li Junjie said: "The concept of'precision treatment' is in the current state of the art.
It has been mentioned more and more in the treatment of tumors, but it is very difficult to achieve precise treatment in the adjuvant treatment of early breast cancer.  Neoadjuvant therapy can reflect the signal pathway and therapeutic efficacy of tumors through the detection of bio-markers.
However, in the adjuvant therapy stage, patients are in a state of "tumor-free".

After the detection of the primary lesion, the following two situations may occur: First, the patient is very sensitive to endocrine therapy, which means that standard endocrine therapy has a very good effect, but whether enhanced endocrine therapy can achieve better efficacy is still Unknown.

 Second, if the patient is not sensitive to endocrine therapy, whether the adjuvant treatment stage can obtain new treatment opportunities through the application of CDK4/6 inhibitors that have a mechanism of reversing resistance is still uncertain.

 Based on the above two points, individual precision treatment in the adjuvant treatment stage is still a difficult problem.

The monarchE study also includes the detection and analysis of related bio-markers to screen out patients who can benefit or cannot benefit earlier, so as to guide the follow-up medication plan.

I believe that for a period of time in the future, the current tumor burden is still the most important consideration in formulating adjuvant endocrine intensive treatment strategies.
However, as clinical evidence continues to accumulate, more'targeted' individualized precision therapy will follow.
The perfection.

 Another direction worth exploring is the prolongation of endocrine-assisted intensive treatment.
Whether high-risk groups should use drugs for 10 years, 15 years or even longer is still lacking confirmation from large-scale clinical data, and clinical applications are more inclined to inferences and experience.

As a large-scale global clinical trial involving more than 5600 patients, the monarchE study is worthy of analyzing clinical problems from different angles and dimensions, and may also give more clinical hints.

"Past review: Professor Li Junjie: HR+ Adjuvant Endocrine Therapy Strategies for Early Breast Cancer | SG-BCC Express Expert Profile Professor Li Junjie Associate Chief Physician of Breast Surgery, Fudan University Cancer Hospital, Doctor of Medicine, Cancer Center, Massachusetts General Hospital, USA , Focusing on clinical and basic research of breast cancer, Breast Surgery Teaching Secretary, Director of Pudong Ward, Assistant to the Director, Youth Committee of the Chinese Anti-Cancer Association Breast Cancer Professional Committee Youth Committee of the Chinese Medical Association Breast Oncology Group Youth Committee of the Shanghai Anti-Cancer Association Breast Cancer Specialty Committee Standing Committee and Secretary-General Beijing Cancer Society Breast Youth Committee Reference Materials: [1] JohnstonSRD, Harbeck N, Hegg R, et al.
Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR, HER2-, Node-Positive, High-Risk, Early BreastCancer (MonarchE).
J Clin Oncol.
2020;38(34):3987-3998.
[2] UpdatedmonarchE trial data shows abemaciclib continues to benefit patients with high-risk,HR-positive, HER2-negative, early-stage breast cancer.
News release.
SanAntonio Breast Cancer Symposium.
December 9, 2020.
Accessed December 9, 2020.
[3]48PAbemaciclib combined with adjuvant endocrine therapy in patients from Asia withhigh risk early breast cancer: monarchE.
YS.
Yap.
SB.
KimDOI: https://doi.
org/10.
1016/j.
annonc.
2021.
03.
062*This article is only used to provide scientific information to medical professionals, and does not represent the views of this platform