Based on the present, looking to the future: How to deploy troops for the late-line treatment of advanced colorectal cancer?

*Only for medical professionals to read for reference.
Three experts share the clinical practice and latest progress of advanced colorectal cancer, come and see! In recent years, with the continuous in-depth research on targeting and immunotherapy and genotyping, patients with advanced colorectal cancer (CRC) have ushered in more and better treatment options
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At present, immunotherapy has been approved for the first-line treatment of advanced CRC with high microsatellite instability (MSI-H) or mismatch repair gene defect (dMMR).
Targeted drug combination immunotherapy has also made important progress in advanced CRC.

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To this end, during the BOC/BOA 2021 China conference, the “medical community” specially invited Professor Li Jin from the Oriental Hospital of Tongji University, Professor Zhang Suzhan from the Second Affiliated Hospital of Zhejiang University School of Medicine, and Professor Li Qiu from West China Hospital of Sichuan University to discuss CRC.
Current status of treatment, research progress, and subsequent treatment strategy
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There is a high incidence of advanced CRC in China, and third-line treatment is still a clinical pain point.
Professor Li Jin’s wonderful video CRC is one of the most common malignant tumors in the world
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The latest statistics of WHO in 2020 show that the number of new cases of CRC in China each year exceeds 550,000, ranking second among all malignant tumors in China
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And with the development of the socio-economic level and the changes in people's life>
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Professor Li Jin told the medical community: “Some CRC patients can be treated with surgery after diagnosis, but most CRC patients will eventually develop into advanced stages, and a considerable number of patients will have recurrence or metastasis after surgery
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” How can patients with advanced CRC be treated effectively? Professor Zhang Suzhan pointed out: “For patients with advanced bowel cancer, it is recommended to detect tumor KRAS, NRAS, BRAF genes and microsatellite status before treatment.

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Patients who have failed first-line treatment can consider testing for the HER2 gene and NTRK gene
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Clinically, the status of these molecular markers can affect the choice and prognosis of patients' treatment options
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"For the choice of treatment options for advanced CRC, Professor Li Jin said: "The first and second-line treatment options for advanced or recurrent CRC are combined chemotherapy, that is, oxaliplatin, irinotecan, fluorouracil, capecitabine and other chemotherapy methods combined with targets.
Towards treatment (cetuximab or bevacizumab)
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Under this treatment plan, the median overall survival (OS) of patients with colorectal cancer can reach 25-28 months
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However, after the failure of the first and second-line treatments, the third-line options are limited and the effective rate is low
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How to extend the progression-free survival (PFS) of third-line therapy and prolong OS is still an unmet clinical need for patients with advanced CRC
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"Immunotherapy combined with anti-angiogenic TKI drugs have a promising prospect for late-line treatment of advanced CRC.
Microsatellite instability (MSI) is an important molecular marker for CRC.
The KEYNOTE-177 study laid the foundation for single-agent immunotherapy (pembrolizumab).
) The status of first-line treatment in MSI-H/dMMR patients with advanced CRC
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So what is the application prospect of immunotherapy in the late-line treatment of patients with advanced CRC? For this reason, researchers are constantly exploring new and more effective treatment strategies
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This year’s published ASCO meeting a professor Lee led into the anti-angiogenic preliminary results for Ib study of PD-1 inhibitors Nepalese joint letter Dealey monoclonal antibody treatment of advanced CRC generation quinoline drugs furosemide
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Professor Li Jin description: "exploring security After the Phase Ia study on sex and dosage, we launched a Phase Ib extension study
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The medication regimen determined in the study is a 5mg intermittent regimen, that is, Fruquintinib 5mg medication for 2 weeks and 1 week withdrawal + Sintilizumab 200mg Q3W
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The patients enrolled in the study have previously received at least second-line treatment
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The results of the study showed that the objective response rate (ORR) of the 5 mg intermittent treatment group was 27.
3%, and the disease control rate (DCR) was 95.
5%.
The curative effect was satisfactory
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And the safety of the combined program is controllable, and there are no reports of treatment-related deaths
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"Fruquintinib combined with sintilimab has achieved preliminary results in the third-line treatment of patients with advanced CRC
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"However, the results of this study need to be further verified.
We hope to further prove it through registered clinical trials or real-world clinical studies in the future
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"Professor Li Jin emphasized
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To
challenge the treatment of MSS-type advanced CRC patients, immunotherapy combined with anti-angiogenic TKI drugs has lived up to expectations.
Professor Zhang Suzhan's wonderful video Although immunotherapy has achieved breakthrough effects in patients with MSI-H/dMMR advanced CRC, only 5 % Of patients with advanced CRC are dMMR
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For another 95% of patients with microsatellite stable (MSS), single-agent immunotherapy has limited efficacy, and how to prolong their survival has become a clinical difficulty
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In this regard, Professor Zhang Suzhan said: "We expect MSS patients benefit from immunotherapy and must explore new therapies
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Anti-angiogenesis therapy combined with immunotherapy is one of the currently explored schemes.
The local anti-angiogenesis drug fruquintinib has obvious curative effect and mild side effects, which is favored by Chinese scholars
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"This year's ASCO conference also announced the results of a phase Ib study of fruquintinib combined with PD-1 inhibitor genomab in the treatment of metastatic CRC (mCRC) carried out by Chinese scholars
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The
study included 15 patients who had received 1~ Among the mCRC patients who failed two standard treatments, 80% (12 cases) were of MSS type
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The
results of the study showed that the ORR of Fruquintinib combined with Genozumab in MSS patients was 25%, and the DCR could reach 75%.
The PFS was 5.
45 months and the mOS was not reached
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Regarding the initial efficacy of the combined regimen in the posterior treatment of MSS patients, Professor Zhang Suzhan said happily: "This result is encouraging
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If this program is validated in the next phase II/III study, this combination of anti-angiogenic drugs and immunotherapy will become a very promising treatment
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I very much look forward to Chinese scholars with the support of relevant manufacturers to make outstanding achievements, so that my country's immune combined anti-angiogenesis therapy can reach the international leading level! "New treatment strategies continue to emerge.
How do you line up for late-line treatment for patients with advanced CRC? Professor Li Qiu’s wonderful video.
With the continuous development of targeted and immunotherapy, patients with advanced CRC have more and more treatment options
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Then , advanced CRC patients have more and more treatment options .
How should the posterior treatment of CRC patients be laid out? Professor Li Qiu shared: "First, we need to formulate treatment goals based on the patient's condition
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For example, for incurable patients who have undergone multi-line treatment, we need to consider the patient’s quality of life and prolonged life at the same time.
According to age, general conditions and comorbidities, as well as adverse reactions that have not been fully recovered during front-line treatment, we need to choose the appropriate Treatment drugs, but also give patients more supportive treatment
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If the patient merges with metastasis, then the symptoms of metastasis will be dealt with accordingly.
It is hoped that while prolonging the survival of the patient, a relatively good quality of life can be maintained
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Anti-angiogenesis therapy is a very important targeted therapy for CRC
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More and more patients are using the anti-angiogenic drug bevacizumab in first-line or second-line treatment
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A subgroup analysis of the FRESCO Phase III clinical study showed that regardless of whether the patient has received bevacizumab in the past, when fruquintinib is used as a back-line treatment, both PFS and OS have benefits
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Therefore, for patients who have received bevacizumab in the front line after progression, I will still choose anti-angiogenesis therapy in the back line
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"Local innovative drugs bring more hope to Chinese patients.
In recent years, national pharmaceutical companies have risen rapidly, and more and more new drugs have appeared in the field of tumor treatment, and have appeared on the international stage
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At this year’s ASCO conference, the local innovative drug furuquine Tinib released a number of research data
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In this regard, Professor Li Jin said: “First of all, Fruquintinib is truly the first one invented by a Chinese, developed by a Chinese team, and then a clinical research conducted by Chinese clinical researchers.
, And finally successfully marketed drugs for the treatment of advanced CRC
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I sincerely wish that the ongoing clinical research of Fruquintinib in Europe and the United States will be as successful as the FRESCO research carried out in China
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Second, in the research and development of new drugs, European and American countries are still the first phalanx, and China is still on the way to catch up
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At present, the number of clinical business in China is increasing, and there are more and more new anti-tumor drugs, but everyone must remember not to be proud, because we are still a considerable distance from the most advanced regions and countries in the world
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We must catch up, work hard, keep improving and surpass ourselves, so as to provide the safest and most effective products for the vast number of cancer patients in China
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I also hope that through the joint efforts of us and the sponsors, we will advance the creation of new drugs in China, so that China's new anti-tumor drugs will be launched in the fastest, most convenient and scientific way, and help Chinese patients as soon as possible
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"Expert Profile Professor Li Jin, Director of the Department of Oncology, Shanghai Oriental Hospital, Tongji University Oriental Hospital, CSCO Gastric Cancer Expert Committee Chairman, Asian Cancer Alliance (FACO) Chairman, Chinese Society of Clinical Oncology (CSCO) Former Chairman, CSCO Drug Safety Committee Chairman, Beijing Xi Chairman of Cisco Clinical Oncology Research Foundation Vice Chairman of Colorectal Cancer Professional Committee of Chinese Medical Doctor Association Vice Chairman of Abdominal Tumor Committee of Chinese Medical Continuing Education Association Professor Zhang Suzhan Chief Physician and Doctoral Supervisor of the Second Affiliated Hospital of Zhejiang University School of Medicine Zhejiang The Director of the Institute of University Cancer Research is currently the regional chairman of the International Association of University Colorectal Surgery (IUSCR), the standing director of the Chinese Anti-Cancer Association, the former chairman of the National Colorectal Cancer Professional Committee, the Standing Committee of the Chinese Medical Association Oncology Branch, the National Health and Family Planning Commission, the early diagnosis and early treatment of colorectal cancer.
Team leader specializes in the comprehensive research and treatment of colorectal cancer for a long time.
Professor Li Qiu, Doctor of Medicine, Chief Physician, and Doctoral Supervisor of West China Hospital, Sichuan University, Deputy Director, Cancer Center, West China Hospital, Sichuan University, Sichuan Academic and Technical Leader, Chinese Medical Doctor Association Liver Cancer Chairman of the Committee of Internal Medicine, Chinese Anti-Cancer Association, Vice Chairman of the Committee of Internal Medicine for Oncology Support Therapy, Standing Committee of the Chinese Society of Clinical Oncology (CSCO) Expert Committee of Integrated Traditional Chinese and Western Medicine, Standing Committee of the Committee of Molecular Targeted Therapy of Cancer, Chinese Society of Biomedical Engineering, Sichuan Province Anti-Cancer Chairman of the Anti-Cancer Drug Professional Committee of the Cancer Association Chairman of the Pharmacoeconomics Professional Committee of Chengdu Medical Association Focusing on biological targeted therapy, chemotherapy and comprehensive treatment of gastrointestinal malignant tumors Presided over a number of 863 projects, 973 sub-projects, National Natural Science Foundation of China Committee, provincial and ministerial scientific research projects have published more than 60 papers in magazines such as Int J Cancer *This article is only used to provide scientific information to medical professionals, and does not represent the views of this platform