Professor Shao Zhimin: Triple-negative breast cancer immunotherapy has a bright future, and the FUTURE-C-PLUS research brings the "strongest" voice!

*Only for medical professionals to read and refer to the new breakthroughs in triple-negative breast cancer immunotherapy, Professor Shao Zhimin's comprehensive interpretation! Triple-negative breast cancer accounts for about 15% of all breast cancers.
It is called "three-negative" because the three main therapeutic targets of estrogen receptor (ER), progesterone receptor (PR) and HER2 are negative
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Due to lack of targets and high risk of recurrence and metastasis, such patients are considered to be the type of breast cancer with the worst prognosis
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Among them, triple-negative breast cancer, which is still progressing after many rounds of treatment, is even closer to "exhaustion", and the objective response rate (ORR) after conventional treatment is less than 10%
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In order to solve the clinical treatment dilemma, the team of Professor Zhimin Shao from the Cancer Hospital of Fudan University has been dedicated to the basic and clinical translational research of triple-negative breast cancer for 5 years, and successfully mapped the world’s largest triple-negative breast cancer gene map in 2019, confirming it In fact, patients of this type can be further subdivided into types
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Through the analysis of huge genetic data, the research team put forward the "Fudan classification" standard for the first time in the world according to different genetic characteristics, and based on this, it divided triple-negative breast cancer into 4 different subtypes: immunomodulatory (IM), Lumen androgen receptor type (LAR), basal-like immunosuppressive type (BLIS), interstitial type (MES)
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In July 2020, the world's top academic journal Cell Research published the results of the FUTURE study based on Fudan classification, which opened the door for precision treatment of triple-negative breast cancer for the first time and brought new hope to patients with triple-negative breast cancer
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At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Prof.
Zhimin Shao’s team will bring "Combination of famitinib with camrelizumab plus nab-paclitaxel as first-line treatment for patients with immunomodulatory advanced triple-negative breast cancer(FUTURE-C-PLUS): A Prospective, single-arm, phase 2 study" (abstract number: 1007) report appeared in the special session of metastatic breast cancer.
The "medical community" sincerely invites Professor Shao Zhimin to interpret the study in depth
.

Figure 1 Screenshot of ASCO’s oral report.
The FUTURE study is asking questions.
“C-PLUS” came into being, Professor Shao Zhimin said: “The previous median number of treatment lines for patients in the FUTURE study announced last year was 3, and 43% of the patients had 3 and The above-mentioned organ metastasis
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From the baseline situation, the included patients are all refractory to the posterior line
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When we initially analyzed the efficacy, we found that the C arm is the immunomodulatory arm, PD-1 monoclonal antibody combined with chemotherapy The ORR of patients after failure of multi-line therapy can reach 52.
6%, which is far superior to previous chemotherapy regimens
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After-line guaranteed treatment can achieve such a considerable therapeutic effect.
If such a treatment regimen is placed in the first-line treatment, immunomodulatory triple-negative breast Can cancer patients benefit more? So the FUTURE-C-PLUS study came into being.
The enrolled patients were all IHC CD8 ≥ 10%, which is highly correlated with PD-L1 expression, and PD-L1 expression was positive
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" The intervention of the C arm in the FUTURE study is PD-1 monoclonal antibody combined with chemotherapy.
Although the effect is considerable, Professor Shao Zhimin’s team still found some problems: drug resistance, lack of effective bio-markers, and toxic side effects.
Produced
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How to further solve these problems, so as to ensure safety while improving efficacy? Professor Shao Zhimin’s team conducted a series of explorations.
Animal experiments confirmed that anti-VEGF antibodies increased CD8 infiltration and PD-L1 expression in a variety of tumor tissues.
At the same time, the effect of anti-angiogenesis combined immunotherapy (chemo-free) was observed.
An increase in adverse reactions was observed
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"Therefore, we added the anti-angiogenic drug famitinib to the FUTURE-C-PLUS research intervention measures to explore the PD-1 monoclonal antibody carrelizumab + famitinib + albumin paclitaxel.
The clinical treatment effect of the combined program
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" Professor Shao Zhimin said
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"Under the giant tree, there is an initial fruit": ORR is as high as 81.
3%! If the FUTURE clinical trial is compared to a giant tree with open branches and leaves, then the FUTURE-C-PLUS research can be described as fruitful
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Judging from the baseline situation of the patients enrolled in the FUTURE-C-PLUS study, 47.
9% of the patients had ≥3 metastases, 50% of the patients had lung metastases, and 20.
8% of the patients had liver metastases.
The conditions of the enrolled patients were generally worse.
Serious
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Figure 2 Baseline situation of patients Although most of the enrolled patients have systemic organ metastasis, the ORR is as high as 81.
3% in terms of efficacy data, which is currently the highest ORR for first-line treatment of metastatic triple-negative breast cancer; 39 patients in the ITT population obtained The confirmed ORR included 5 cases of complete remission (CR) and 34 cases of partial remission (PR)
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Figure 3 Study ORR data Although the results of progression-free survival (PFS) are not yet mature, the 9-month PFS rate is 60.
2% (95% CI 43.
2%-77.
3%), and the 10-month PFS rate is 53.
4% ​​(95 %CI 37.
6%-69.
3%)
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Professor Shao Zhimin said: "Our preset PFS study endpoint is that 23-25 ​​of 46 patients have disease progression, but it has not yet been reached
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PFS is expected to be about 11 months.
This data can be said to have brought a revolutionary breakthrough in metastatic triple-negative breast cancer
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We are also pursuing higher-level clinical data of evidence-based medicine for the first-line treatment of immunomodulated metastatic triple-negative breast cancer, in order to truly change the clinical treatment plan and guide clinical practice
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The follow-up FUTURE-super clinical trial we carried out is a head-to-head comparison with standard first-line chemotherapy to further verify the effect of the three-drug combination regimen
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"From the point of view of safety data, the median period of exposure to each drug is 8 cycles
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The adverse events (AEs) in the combined regimen are consistent with expectations and are relatively well tolerated
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Figure 4 Treatment exposure & treatment-related adverse events Overview of events (TRAEs) Immunotherapy may completely revolutionize the treatment pattern of triple-negative breast cancer.
Previous foreign studies, such as the KEYNOTE-522 study, explored the value of PD-1 monoclonal antibody combined with chemotherapy in the neoadjuvant treatment of early high-risk triple-negative breast cancer ; The IMpassion130 study evaluated the efficacy of PD-L1 monoclonal antibody combined with chemotherapy in the treatment of metastatic triple-negative breast cancer
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So, what is the prospect of immunotherapy in the treatment of triple-negative breast cancer? In this regard, Professor Shao Zhimin said: "KEYNOTE-522 Although the study confirmed that the combination of PD-1 monoclonal antibody and chemotherapy can significantly increase the pathological complete remission (pCR) rate, it failed to confirm whether the positive expression of PD-L1 can predict the efficacy in early triple-negative breast patients
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The IMpassion130 study has confirmed that the combination of PD-1 monoclonal antibody and albumin paclitaxel can significantly improve the efficacy
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Immunotherapy has undoubtedly broadened the prospects for treatment of triple-negative breast cancer, but any treatment is gradually moving forward, from back-line to first-line treatment, to neoadjuvant and adjuvant therapy
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Our team is also constantly exploring more possibilities of immunotherapy in the treatment of triple-negative breast cancer, such as whether patients with immune cold tumors can be transformed into immune hot tumors through some specific drugs; for the anti-angiogenic drug famitinib , Our team has also conducted basic translational research to expand the applicable population of immunotherapy and benefit more patients
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"The FUTURE study has a total of 7 treatment arms.
The results of the FUTURE-C-PLUS study are announced this time.
How effective is the other treatment arms? Can it be further settled? In this regard, Professor Shao Zhimin said: "At present, we can basically judge 7 Of the two treatment arms, three were able to obtain positive results, and we continued to enroll patients in the other treatment arm
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We will also conduct further verification in follow-up studies based on the results of the FUTURE study to continue to promote the precision treatment of triple-negative breast cancer
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"The road from basic medicine to finalized clinical practice is "long and long" and requires the efforts and efforts of countless researchers.
However, we believe that in the future, triple-negative breast cancer can be accurately classified and treated with precision.
Chinese patients with triple-negative breast cancer Survival status must be greatly improved! Expert profile Professor Shao Zhimin, the first batch of Ministry of Education Changjiang Scholars Distinguished Professor, National Outstanding Youth, Fudan Distinguished Professor, Fudan University Cancer Institute Director, Breast Cancer Institute Director General Surgery Director and Breast Surgery Director Honorary Chairman of the Chinese Anti-Cancer Association Breast Cancer Professional Committee, Director of the Chinese Anti-Cancer Association Targeted Therapy Professional Committee Director of the Chinese Society of Clinical Oncology (CSCO), Vice Chairman of the Chinese Medical Association Oncology Branch, Chinese Medical Doctor Association Clinical Precision Medicine Professional Committee Breast Cancer Chairperson of the Professional Committee Honorary Chairperson of the Breast Cancer Professional Committee of the Shanghai Anti-Cancer Association Honorary Chairperson of the Oncology Committee of the Shanghai Medical Association References: [1].
https://meetings.
asco.
org/2021-asco-annual-meeting /13607?presentation=196659#presentations