Professor Yin Yongmei, Zhang Xizhi, Guo Zhaoji: Combined therapy with piperacillide, prolonging the survival of patients is no longer a dream

*Only for medical professionals to read for reference.
From RCT to RWS, piperacillil promotes the multidisciplinary development of advanced breast cancer and achieves the goal of long-term survival for patients.

In the era of endocrine targeted therapy for breast cancer, as the first CDK4/6 inhibitor to be marketed in China, whether it is a randomized controlled trial (RCT) or a real world study (RWS), it has accumulated abundant evidence-based medical evidence , And promoted the update of the "Guidelines for the Standardized Diagnosis and Treatment of Advanced Breast Cancer in China (2020 Edition)", which has attracted the attention of experts in multiple disciplines.

The "medical community" specially invited Professor Yin Yongmei from Jiangsu Provincial People's Hospital, Professor Zhang Xizhi from Subei Hospital, and Professor Guo Zhaoji from the First Affiliated Hospital of Soochow University to discuss and express opinions on related topics.

A number of real-world studies show significant clinical benefit of piperacillil.
A real-world study mentioned in the guideline shows that among the 1,430 HR+/HER2-metastatic breast cancer patients enrolled from 2015 to 2019, piperbe was used as the first line More than half of the patients treated with celi combined with letrozole (LET), a total of 772 cases, 658 cases of first-line LET monotherapy patients, the median follow-up time was 24.
2 months (IQR 14.
2-34.
9) and 23.
3 months (IQR) 12.
7-34.
3).

The results showed that the unadjusted OS data (not reached) in the pipercillil combination treatment group was significantly better than that in the LET monotherapy group (40.
3 months, 95% CI 34.
2-not reached) (P<0.
0001).

Professor Yin Yongmei mentioned that, in addition to this, the pipercillil combination therapy group reduced the risk of death by 42% compared with the single-agent group.
Although the overall survival time has not been reached, from the current results, overall survival has been significantly improved.

At the ESMO Asia conference in 2020, the team led by Professor Yin Yongmei announced a small-sample real-world study of the use of piperacillil by patients in our center.

The study retrospectively analyzed from May 2018 to January 2020, among 51 breast cancer patients who received piperacillil combined with endocrine therapy, 14 were treated as first-line treatment and 37 were treated as second-line or above.

The results showed that the objective response rate (ORR) was 10.
6%, the clinical benefit rate (CBR) was 67.
4%, and the median progression-free survival (PFS) was 10 months.

Subgroup analysis showed that the PFS of first-line patients had not yet reached, CBR was 83.
3%; the median PFS of second-line and above patients was 8 months, and the CBR was 61.
3%.

In response to the positive results of the above real-world studies, Professor Yin Yongmei believes that piperacillil is the first CDK4/6 inhibitor that has significant OS benefits in the first-line treatment of postmenopausal HR+/HER2- advanced breast cancer patients in a real-world study.
Real-world research results have added more sufficient evidence for the clinical benefit of first-line treatment of HR+/HER2− advanced breast cancer with piperacillide.

Professor Yin Yongmei has also applied to the CSCO Breast Committee for a larger real-world study, aiming to compare the efficacy of first-line or second-line endocrine therapy and endocrine combined with piperacillin in all domestic advanced breast cancer patients in the past two years.

Observe whether there is a trend of benefit from PFS or OS in combination with pipracillil compared with endocrine monotherapy.

Multidisciplinary diagnosis and treatment helps patients with advanced breast cancer survive longer.
The treatment goal of advanced breast cancer is to prolong OS and improve the quality of life of patients.

Although advanced breast cancer is usually difficult to cure, reasonable treatment can relieve symptoms, improve the quality of life, and can significantly extend the survival time.
Some patients can live with the tumor for a long time, even more than ten years.

For the treatment of advanced breast cancer patients, multidisciplinary cooperation is very important.
Professor Zhang Xizhi mentioned: "Multidisciplinary diagnosis and treatment have been done in various units in recent years, including various diseases, from the lungs to the liver and gallbladder to the gastrointestinal.
Diagnosis and treatment.

Its purpose is to integrate some information through the discussion of various experts, and to choose the best treatment plan after the discussion of the clinician, especially for some specific metastasis sites.
For
example, for brain metastases and bone metastases, radiotherapy can be used.
Achieve very good results. In internal medicine treatment, patients often ignore or delay radiotherapy for bone metastases or brain metastases.
Being able to receive radiotherapy in time can significantly reduce pain and symptoms, which is of great significance to comprehensive treatment.

In the course of medical treatment, the patient develops drug resistance, and whether to conduct a tissue biopsy also requires multi-disciplinary discussion.

"PALOMA series of studies have confirmed that piperacillil brings new hope to patients with HR+ breast cancer.
Professor Zhang Xizhi believes that HR+ breast cancer with the largest proportion of subtypes should be divided into two categories.
One is HR+/HER2- breast cancer without internal organs.
Patients in crisis can preferentially choose CDK4/6 inhibitor combined with endocrine therapy.
In
patients with crisis, if there is lung metastasis and obvious symptoms (cough, hemoptysis, etc.
), chemotherapy is given priority.

In combined endocrine therapy, piperazine As the first CDK4/6 inhibitor to be marketed in China, Perceline has accumulated a lot of evidence-based medical evidence.
The first-line/second-line treatment of HR+/HER2- advanced breast cancer has been approved by the "Guidelines for the Standardized Diagnosis and Treatment of Advanced Breast Cancer in China (2020 Edition)" The IA-level recommendation is the highest-level recommendation.

The recommendation is based on three randomized controlled studies PALOMA-1, 2, 3, and the PALOMA-1 study compared letrozole with or without piperazil in HR +/HER2- postmenopausal The effect of the first-line treatment of breast cancer patients with metastasis or local recurrence that is not suitable for surgery, the results showed that the PFS of the piperacillil group increased from 10.
2 months to 20.
2 months, reaching a two-fold increase.

The latest PALOMA-2 was followed.
Three-year data show that the combination of piperazil and endocrine first-line treatment of HR+/HER2- breast cancer patients significantly prolonged PFS to 27.
6 months, which was nearly doubled compared with the control group, and reduced the risk of disease by 44%.

In the Asian analysis, piperazine was also used to treat HR+/HER2- breast cancer patients.
Compared with the control group, the median PFS of Bacillil combined with letrozole in patients with only bone metastasis was also significantly prolonged, 36.
2 months and 11.
2 months, respectively.
This data is a very good data for patients with advanced breast cancer.
It will bring great hope for the treatment of advanced breast cancer. The PALOMA-3 study is for patients who have progressed in past endocrine therapy, including adjuvant endocrine therapy or stop adjuvant therapy within 12 months, or progress in endocrine therapy at the stage of recurrence and metastasis, the previous drug choice is fulvestrant, and piper is added.
After Seely, PFS was extended to 11.
2 months, and OS was extended by 6.
9 months.

Although it did not reach statistical significance, in patients with previous endocrine sensitivity and secondary drug resistance, the PALOMA-3 study showed that piperacillil combined with endocrine therapy can significantly prolong the patient's OS, and the difference is statistically significant.

How do patients with advanced breast cancer undergo surgical treatment? For the surgical treatment of patients with advanced breast cancer, Professor Guo Zhaoji pointed out that advanced breast cancer includes locally advanced and recurrent or metastatic (stage IV) breast cancer.

The guidelines refine patients with locally advanced breast cancer and divide them into patients who may be converted to radical surgery and those who cannot achieve radical treatment even after neoadjuvant treatment.

For patients who may be transformed into radical surgery at locally advanced stage, neoadjuvant treatment strategies should be actively adopted to transform inoperable into operable.

Therefore, such patients should actively choose the neoadjuvant treatment plan based on the molecular classification.

For patients with HR+, combined chemotherapy with anthracyclines and paclitaxel is used clinically for treatment.

The CBCSG036 study found that neoadjuvant chemotherapy combined with neoadjuvant endocrine therapy can be selected for Luminal breast cancer patients, which can achieve good therapeutic effects for this part of the population.

For patients who cannot achieve radical treatment even after neoadjuvant treatment, it is necessary to refer to the strategy of systemic treatment of metastatic breast cancer.

If the patient cannot achieve the goal of radical surgery through neoadjuvant therapy, follow-up treatment options for advanced breast cancer are selected.

Regarding surgical intervention methods, Professor Guo Zhaoji shared that for newly diagnosed stage IV breast cancer patients, only 2%-6% abroad and 3%-10% domestically.

It is still controversial whether the resection of the primary tumor in newly diagnosed stage IV breast cancer patients can benefit, and the operation for the purpose of prolonging survival time needs to be carefully individualized.

When the transfer load is small and systemic treatment is effective, local surgery tends to benefit.
Some patients may consider palliative surgery due to breast ulceration and bleeding.

If the patient's molecular biological classification is HER2+ or HR+, on the basis of systemic active treatment, active primary resection can be performed for some patients with oligometastasis.

If the patient has pure liver metastasis and pulmonary metastasis, surgical intervention may also be considered for the metastasis, and the chance of radical treatment has been obtained.

For relatively limited locally recurring advanced breast cancer, local radical treatment should be selected as far as possible, including mastectomy, breast-conserving surgery again, and whether local radiotherapy should be considered based on the recurrence, previous radiation dose and location after surgery.

Patients who have achieved radical treatment should actively carry out systemic treatment strategies, actively carry out radiotherapy and chemotherapy, and achieve the purpose of second radical treatment.
Specific plans can refer to adjuvant or neoadjuvant treatment strategies based on the previous treatment history.

For patients who cannot achieve radical treatment, systemic treatment should still be the main treatment method.
On the basis of systemic treatment, local treatment can be combined with patients who urgently need to relieve symptoms or relieve complications.

For advanced breast cancer, systemic therapy should be the initial treatment.
Therefore, in the multidisciplinary treatment of advanced breast cancer, the formulation of medical oncology treatment programs is particularly critical.

At present, for HR+/HER2- advanced breast cancer, CDK4/6 inhibitor combined with endocrine therapy is the mainstream method, which can significantly improve the survival benefit of patients and improve the quality of life of patients.

As the first CDK4/6 inhibitor approved to be marketed in China, piperacillil has accumulated a large amount of evidence-based medical evidence, whether it is RCT or RWS, and has now obtained the IA recommendation of the new version of the guideline, which can be used as HR+/HER2- advanced breast cancer The preferred treatment.

On the basis of optimized treatment in internal medicine, combined with effective local treatment methods, multi-disciplinary joint participation creates greater survival benefits for patients.

The price of piperacillide is cut to give more patients the hope of survival.
In order to allow more advanced breast cancer patients to receive piperacillil, this "good medicine" treatment has been implemented since January 2021, and the price of piperacillil has been reduced significantly.
According to the public policy, Professor Guo Zhaoji shared that the price of this drug will drop significantly in 2021, and the price per bottle will be lowered from nearly 30,000 to around 13,000, a price reduction of more than half.

In Suzhou's commercial insurance policy, patients with breast cancer can be reimbursed 30% for patients with pre-existing diseases, and the monthly cost is about 9,000 yuan, which benefits more patients to receive treatment.

Expert Profile Yin Yongmei, Chief Physician and Professor, Ph.
D.
Supervisor, Deputy Dean of the Women's and Children's Branch of Jiangsu Provincial People's Hospital, Executive Director, Chinese Society of Clinical Oncology (CSCO), Executive Director, Beijing Hesco Foundation, Deputy Director, CSCO Breast Cancer Expert Committee, Vice Chairman, Chinese Anti-Cancer Association Breast Cancer Professional Committee Member of the Standing Committee of the CSCO Patient Education Expert Committee, Zhang Xizhi, Chief Physician, Master Research Instructor, Director of the Oncology Department of Subei Hospital, Vice-Chairman of the Radiation Oncologist Branch of Jiangsu Medical Association and Deputy Chairman of the Radiotherapy Branch of Jiangsu Research Hospital Association Member of the Chemotherapy and Biotherapy Professional Committee of the Jiangsu Medical Association Member of the Liver Cancer Radiotherapy Group of the Radiation Oncology Professional Committee of the Chinese Research Hospital Association Member of the Tumor Metastasis and Recurrence Professional Committee of the Jiangsu Anti-Cancer Association Member of the Chemotherapy Professional Committee of the Jiangsu Anti-Cancer Association Member of the Standing Committee of Jiangsu Anti-Cancer Association-Pharyngeal Cancer Professional Committee Deputy Chairman of the Radiotherapy Professional Committee of Yangzhou Medical Association Deputy Chairman of the Chemotherapy and Biotherapy Professional Committee of Yangzhou Medical Association Guo Zhaoji Chief Physician, Department of Thoracic and Breast Surgery, The First Affiliated Hospital of Soochow University Suzhou City Director of the Breast Cancer Professional Committee of the Anti-Cancer Association Member of the Breast Branch of the Jiangsu Association of Integrative Chinese and Western Medicine Deputy Secretary-General of the Suzhou Society of Biological Therapy Expert Outpatient Time: Wednesday morning/Thursday all day (Shizijie District) *This article is only for medical advice Scientific information provided by people does not represent the views of this platform