Prof. Fan Lei: The best immunotherapy predictor for TNBC remains to be explored, and precision treatment is imperative 2021 SABCS Review and Reflections

*Only for medical professionals to read and refer to the latest research progress! Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with the worst prognosis, accounting for about 15% of all breast cancers.
Once recurrence and metastasis occur, the median survival time is less than 1 year
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One of the reasons for the poor therapeutic effect of TNBC is that it is often accompanied by visceral metastases, and another reason is largely due to the lack of effective therapeutic drugs
.

The 44th San Antonio Breast Cancer Symposium (SABCS 2021) ended on December 10.
As the vane of breast cancer treatment, many blockbuster researches in the field of TNBC were also announced at the SABCS conference.
Prof.
Fan Lei from the Cancer Hospital conducted an in-depth interpretation of the relevant research, and explained in detail the research results obtained by the breast surgery team of the Fudan University Affiliated Cancer Hospital in recent years
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Rapid onset, poor prognosis, and rapid progression—the unbearable weight of TNBC TNBC usually relapses early within 1-3 years.
Once it enters the state of relapse, the survival prognosis is very worrying
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There is also a huge gap between TNBC and other subtypes of breast cancer with hormone receptor (HR)-positive and HER2-positive breast cancer survival and prognosis
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The overall survival time of HR-positive/HER2-positive breast cancer patients can exceed five years, but due to the lack of effective therapeutic targets for TNBC, the overall survival time is only about one year
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Professor Fan Lei said: "The current treatment for TNBC is still chemotherapy, and a small number of patients with recognized biomarker expression such as BRCA gene mutation and positive PD-L1 status can receive PARP inhibitors and immune checkpoint inhibitors accordingly.
treatment
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Due to the problem of drug availability, although TROP-2 is highly expressed in TNBC, domestic patients are still unable to receive treatment with new targeted drugs such as antibody-conjugated (ADC) drug goxatuzumab, and the overall survival situation is not good.
Optimism - such a treatment dilemma has also become a 'thorn' in the hearts of our oncologists, and the treatment of TNBC is currently the hottest and most difficult exploration direction in the field of breast cancer
.

"What enlightenment does SABCS give us in the treatment of TNBC? Talking about the SABCS conference that ended soon, Prof.
Fan Lei said: "SABCS is a long-standing, extensive and comprehensive conference in the field of breast cancer, and many blockbuster research will be officially announced at the conference.

.

At this year's SABCS Congress, Prof.
Zhimin Shao gave a presentation on 'The Genomics and Transcriptomic Mapping of Triple-Negative Breast Cancer: Molecular Subtypes and Its Precision Therapy' in the educational course 'Triple Negative Breast Cancer: Key Advances in Biology and Therapy' Wonderful explanation
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Therefore, for breast cancer workers, SABCS is a high-quality learning platform focusing on cutting-edge global progress
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"Professor Fan Lei selected the following three studies in the field of TNBC to share: 01GS1-01: Neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab in the treatment of early high-risk TNBC is often found in the KEYNOTE-522 study.
First randomized, placebo-controlled phase III study of bolizumab as neoadjuvant and adjuvant therapy in early-stage TNBC, based on significant event-free survival (EFS) and pathological complete response (pCR) benefits, USA The Food and Drug Administration (FDA) approved pembrolizumab + chemotherapy neoadjuvant therapy, and continued pembrolizumab postoperative adjuvant therapy for early-stage high-risk TNBC patients
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This conference mainly reported the prespecified subgroup analysis and Results of an EFS event sensitivity analysis to assess the robustness and consistency of EFS benefits
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Two of the five prespecified sensitivity analyses assessed the impact of different censorship rules and three assessed the impact of different event definitions; treatment effects on EFS were examined in prespecified patient subgroups that By lymph node metastasis (positive or negative), disease stage (II or III), menopausal status (premenopausal or postmenopausal), HER2 status (IHC was 2+, but IHC was FISH- or 0-1+) and LDH (> ULN or ≤ULN) definition
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In all 5 sensitivity analyses and each subgroup assessed, the benefit of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab versus neoadjuvant chemotherapy alone was generally comparable to the initial EFS outcome Consistent
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Professor Fan Lei said: "The KEYNOTE-522 study still leaves a 'blank' area to be explored, mainly in the following three aspects: First, is pCR a reasonable end point in the early TNBC neoadjuvant therapy research design? With the early intervention of immunotherapy, the long-term prognosis of patients such as EFS and OS will be improved.
Whether pCR can fully reflect the degree of benefit of patients deserves further exploration
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Second, PD-L1 status expression is not neoadjuvant for early TNBC immunotherapy combined with chemotherapy The biomarkers of the treatment plan mean that patients can benefit from it regardless of PD-L1 expression status
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Therefore, the current early-stage TNBC neoadjuvant therapy is an 'all-come' state, whether it is possible to carry out the benefit group on this basis.
More accurate screening? How to formulate a follow-up treatment plan after a patient reaches pCR or non-pCR, whether to continue immunotherapy, and whether to join an intensive treatment plan is worth further research
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"02GS1-02: PD-L1 CPS≥10 is the screening for metastasis Reasonable cut-off value for the benefit of pembrolizumab + chemotherapy in patients with metastatic TNBC In the KEYNOTE-355 study, pembrolizumab + chemotherapy compared with chemotherapy alone in first-line treatment of metastatic TNBC with PD-L1 CPS ≥ 10, Significant improvement in PFS and OS, whereas no significant improvement in PFS or OS was observed in the population with CPS ≥ 1
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This analysis performed subgroup analyses of patients stratified based on additional CPS cut-off values
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In each PD-L1 CPS subgroup, the proportion of patients in the pembrolizumab + chemotherapy group and chemotherapy alone group was comparable, with 24.
9% of patients having CPS <1, 36.
2% and 38.
4% having CPS 1- 9, 14.
1% and 13.
9% of patients had CPS 10-19, and 24.
7% and 22.
8% had CPS ≥20
.

OS subgroup analysis showed that in patients with PD-L1 CPS <1 and 1-9, pembrolizumab plus chemotherapy and chemotherapy alone had similar OS results, while in patients with PD-L1 CPS 10-19 and ≥20 Among patients, pembrolizumab+chemotherapy had a more favorable OS trend
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The PFS subgroup analysis was basically consistent with the OS subgroup analysis, and patients with PD-L1 CPS 1-9, 10-19, and ≥20 were more likely to benefit from pembrolizumab + chemotherapy in PFS
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Prof.
Fan Lei said: "Is the expression status of PD-L1 the best biomarker for advanced TNBC immunotherapy? Different studies have also explored biomarkers including the degree of CD8+ T cell infiltration and gene expression profile
.

Prof.
Zhimin Shao The patients enrolled in the FUTURE-C-PLUS study under the leadership are all immunohistochemical (IHC) CD8 ≥ 10%, that is, immunomodulatory (IM) patients who are highly correlated with PD-L1 expression and are positive.
The objective response rate (ORR) is as high as 81.
3%, and the median PFS update data published on SABCS this year is 13.
6 months, which is the only first-line treatment study for advanced TNBC with a median PFS of more than one year
.

And the one-year OS rate is 82.
6 %, implying long-term benefit for patients
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Another NIMBUS study, building on previous studies in solid tumors, including breast cancer patients, combined nivolumab with ipilimumab in tumor mutational burden-high (TMB-H) metastatic breast cancer.
Efficacy met the primary endpoint with a confirmed ORR of 13.
3%, with a response rate of 60% in the TMB ≥ 14 mut/Mb group and 4% in the TMB ≥ 9 and <14 mut/Mb group (p = 0.
01 )
.

Although the subgroup analysis suggests the TMB threshold of immunotherapy, in actual clinical work, patients with TMB ≥ 14 mut/Mb are very rare, and how to accurately screen the immunotherapy benefit population still needs further exploration
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”03GS1-05: The new ADC drug Dato-DXd appears at dawn The announcement of the preliminary results of the TROPION-PanTumor01 study at this conference allows us to see the good therapeutic effect and safety of the new ADC drug Dato-DXd
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The efficacy can be evaluated in 38 cases Among the TNBC patients, the ORR assessed by BICR was 39% [15 patients with partial response (PR)], and the disease control rate was 84% ​​(32/38).
52%
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In terms of safety, Dato-DXd showed a controllable safety profile, the most common adverse reactions were nausea and stomatitis, and no AEs related to death were seen in the study
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Riding the wind and waves, traveling steadily and far, and re-swelling study Fruitful results In order to solve the predicament of clinical treatment of TNBC, the team of Professor Shao Zhimin from Fudan University Affiliated Cancer Hospital devoted 5 years to the basic and clinical translational research of triple-negative breast cancer, and in 2019, they successfully mapped the world's largest triple-negative breast cancer gene The map confirms that this type of patients can actually be further subdivided into types
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Through the analysis of huge genetic data, the research team proposed the "Fudan tetrad" for the first time in the world based on the four gene characteristics androgen receptor (AR), CD8, FOXC1 (a marker of basal cells) and DCLK1 (a marker of tumor stem cells).
"Criteria, and according to which triple-negative breast cancer is divided into 4 distinct subtypes: IM, luminal androgen receptor (LAR), basal-like immunosuppressive (BLIS), and mesenchymal (MES)," Fudan quartiles are also widely used in other breast cancer treatment centers in China
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In July 2020, the top international academic journal Cell Research published the results of the FUTURE study based on Fudan classification, which opened the door for the precision treatment of triple-negative breast cancer for the first time and brought new hope to triple-negative breast cancer patients
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At the 2021 American Society of Clinical Oncology (ASCO) annual meeting, the FUTURE-C-PLUS study made a stunning appearance in the special session of metastatic breast cancer
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Prof.
Fan Lei said: "Under the leadership of Prof.
Zhimin Shao, our center has conducted basic translational research and clinical research on both early and late stage TNBC in recent years
.
In the
field of early breast cancer, Prof.
Yu Keda's PATTERN research further The status of platinum-based adjuvant therapy has been clarified [1], and it has been included in the 2022 edition of the National Comprehensive Cancer Network (NCCN) guidelines [2], marking the positive impact of Chinese scholars on international TNBC clinical practice; Professor Li Junjie’s CBCSG010 study confirmed TNBC aid for use in combination with capecitabine program can improve long-term prognosis of patients [3]
.

in the future, we will also carry out fUTURE-super clinical trial to compare head to head in exploring PD-1 monoclonal antibody single bead Ka Ruili The efficacy and safety of the anti-famitinib + albumin-paclitaxel three-drug combination regimen and standard first-line chemotherapy will further verify the effect of the three-drug combination regimen
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From the back-line to the adjuvant and neoadjuvant therapy, it is advanced step by step, implementing the principle of precise TNBC treatment, and switching the treatment method by analyzing the characteristics of TNBC molecular typing, aiming to improve the therapeutic effect and improve the survival of patients
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"Reference: [1] Yu K, Ye F, He M, et al.
Effect of Adjuvant Paclitaxel and Carboplatin on Survival in Women With Triple-Negative Breast Cancer: A Phase 3 Randomized Clinical Trial.
JAMA Oncol.
2020;6( 9):1390–1396.
doi:10.
1001/jamaoncol.
2020.
2965[2]Li J, Yu K, Pang D, et al.
Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open- Label, Randomized, Multicenter, Phase III Trial.
J Clin Oncol.
2020 Jun[3]NCCN clinical practice guidelines in oncology.
breast cancer version 1.
2022—november 24,2021Expert Profile Prof.
Lei FanFudan University Doctor of Oncology, Master Supervisor Fudan Deputy Chief Physician of Breast Surgery, University Cancer Hospital, Massachusetts General Hospital Cancer Center, Fellow, Chinese Medical Association, Breast Group, Youth Committee Member, International Medical Exchange Branch, China Anti-Cancer Association Member, Breast Professional Committee, China Research Hospital Association Member of the Youth Committee of the Breast Cancer Special Committee of Shanghai Anti-Cancer Association Member of the Special Committee of Psychosomatic Medicine of Shanghai Medical Association Member of the Popular Science Committee of Shanghai Women Physician Association Chaired and participated in a number of national and Shanghai-level funds for more than 20 papers included in SCI.
I and the corresponding author have more than 10 articles, which are included in "The Lancet Oncology", "JAMA Oncol", etc.
*This article is only for providing scientific information to medical professionals and does not represent the views of this platform