Professor Shen Lin: The whole management strategy of esophageal cancer in the immunotherapy era 2021 CSCO famous doctor Kungfu tea

*Only for medical professionals to read and refer to Professor Shen Lin as a guest doctor Kung Fu Tea, sharing the entry points and development ideas of clinical research related to esophageal cancer immunotherapy
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Esophageal cancer is one of the common malignant tumors of the digestive tract in China.
It is currently the sixth most common tumor and the fourth most deadly tumor in China
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However, the 5-year survival rate for esophageal cancer is only about 20%
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In recent years, immunotherapy has shown good effects in the field of esophageal cancer diagnosis and treatment.
A number of domestic and foreign studies have established the status of immunotherapy in the second-line treatment of advanced esophageal cancer
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At the 2021 Chinese Society of Clinical Oncology (CSCO) Annual Meeting, "Medical Oncology Channel" invited Professor Shen Lin from Peking University Cancer Hospital to be a guest doctor Kung Fu Tea, and discussed the immunotherapy of esophageal cancer diagnosis and treatment with Dr.
Wu Zhouqiao from Peking University Cancer Hospital The latest developments and her experience of clinical research in the era of precision therapy
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Professor Lin Shen (left) and Dr.
Zhouqiao Wu (right) scan the QR code to view the wonderful video ORIENT-15 Study: High-level evidence-based evidence confirms each other and will rewrite clinical practice Dr.
Zhouqiao Wu: In the just concluded Europe in 2021 At the Annual Clinical Oncology Conference (ESMO 2021), you verbally reported the latest results of the ORIENT-15 study.
Could you please interpret this study? Professor Shen Lin: Esophageal cancer is a high-incidence tumor in our country
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In the past 50 years, there has been no outstanding progress in research in this field
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At present, immunotherapy has brought leaps and bounds to the field of esophageal cancer diagnosis and treatment
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The ORIENT-15 study [1] is a global, double-blind clinical study of the first-line treatment of advanced esophageal cancer, comparing Sintilimab combined with chemotherapy (paclitaxel + cisplatin/5-fluorouracil + cisplatin) and placebo combined with chemotherapy Effectiveness and safety
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The chemotherapy regimen is chosen by the investigator
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Because of the epidemic, foreign research centers have fewer cases, so fewer cases have been enrolled in the cisplatin + 5-fluorouracil regimen.
Nearly 94% of the patients in the study used the TP regimen (paclitaxel + cisplatin)
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Interim results showed that in the overall population, sintilimab combined with chemotherapy prolonged the median overall survival (mOS) of patients: from 12.
5 months in the chemotherapy-only group to 16.
7 months
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The Keynote-590 study [2] is a global clinical study for esophageal cancer.
Immunotherapy combined with 5-fluorouracil + cisplatin also obtained positive results.
The mOS was 12.
4 months vs.
9.
8 months (HR 0.
73, 95% CI 0.
62) -0.
86; P＜0.
0001)
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Compared with the Keynote-590 study, the ORIENT-15 study included more Chinese patients and achieved a greater improvement in OS
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In the past, the survival period of first-line treatment for advanced esophageal cancer was about 10 months, and the ORIENT-15 study also significantly improved the survival period of the control group.
The risk of death in the immune combined chemotherapy group was still reduced by 37.
2% (HR=0.
628).
The difference between the two groups is so obvious and very encouraging
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On the whole, our country's treatment effect for esophageal cancer is better than that of foreign countries, thanks to the rise of domestically researched drugs and the treatment of domestic clinicians
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In addition, the safety data of immune combination therapy is consistent with that of foreign countries, and no special adverse reactions have been seen
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The ORIENT-15 study further validated the efficacy of immune combined chemotherapy for esophageal cancer and will change clinical practice in China
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After the enrollment of foreign centers is completed, if the cisplatin + 5-fluorouracil group also achieves the same positive result, then this research will affect global clinical practice and is worthy of our expectations
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The exploration of immunotherapy in the perioperative period: to increase the chance of cure, and the future can be expected.
Dr.
Wu Zhouqiao: Immunotherapy has changed the clinical practice of esophageal cancer treatment, and has gradually moved forward from the back-line treatment to the front-line
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Do you have any expectations for the use of immunotherapy in the perioperative period? Professor Shen Lin: I am definitely looking forward to this
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The research of any new drug in solid tumors evolves from the last line to the first line
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As long as the efficacy and safety of the drugs are guaranteed, they will want to move forward to the perioperative period
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Regardless of whether it is advanced first-line or second-line, it may only be an extension of survival for patients, but it is different in the perioperative period: if the 5-year survival rate is improved, it will bring the patient a chance of cure
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Therefore, even if it is to increase the 5-year survival rate by 10%, it is a very meaningful thing
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There are already relevant explorations on neoadjuvant immunotherapy for esophageal cancer in China.
There is a clinical trial plan in this area on the Clinicaltrials website (https://clinicaltrials.
gov/).
If you are interested, you can recommend patients to participate
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Of course, research in this area requires a longer follow-up time, and the results are relatively slow, but the changes to the entire treatment model are very huge
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Dr.
Wu Zhouqiao: Some studies on other gastrointestinal tumors (such as gastric cancer) have shown that after patients achieve clinical remission (CR) through neoadjuvant therapy, they may not need surgery.
Is there a trend for esophageal cancer? Professor Shen Lin: Indeed, compared with other gastrointestinal tumors, esophageal cancer is more traumatic and has a greater impact on the quality of life of patients
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In recent years, with the use of thoracoscopy and mediastinum, the damage caused by surgery has been reduced a lot
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However, esophageal cancer is particularly prone to recurrence after surgery, so now we hope that immunotherapy can improve the cure rate on the one hand, and on the other hand, it can reduce the focus and further reduce the scope of surgery
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However, to achieve this goal, interdisciplinary collaboration is required, and doctors in internal medicine, surgery, radiotherapy, imaging, pathology and other disciplines need to discuss the patient's individualized plan
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But after neoadjuvant treatment, patients with esophageal cancer reach pathological complete remission (pCR), can they not undergo surgery? I don’t think we can be too optimistic at the moment
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In clinical practice, some patients who achieved pCR relapsed after a while
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In addition, the true pCR rate of esophageal squamous cell carcinoma is relatively low
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The recurrence rate is very high among patients who do not undergo surgery and only undergo radiotherapy and chemotherapy, which shows that non-surgical treatment is not enough
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Therefore, as to what kind of patients should be actively operated and what kind of patients can be observed and treated, more accumulation is needed in this regard, and prospective research is also needed to provide more evidence-based evidence
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In the past, we only had radiotherapy and chemotherapy, but now there is an additional weapon of immunotherapy, but whether it can replace surgery requires further observation and exploration
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Dr.
Wu Zhouqiao: Can radiotherapy combined with immunotherapy be synergistic and improve the overall therapeutic effect? Professor Shen Lin: This requires long-term observation.
The conclusive efficacy of radiotherapy combined with immunotherapy may not be seen only based on the current or recent research results in the past two years
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We are full of expectations in many studies on immunotherapy
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Perioperative treatment needs to be individualized, but it is necessary to prove whether immunotherapy can benefit perioperative patients.
Related research is ongoing
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I believe that the benefits of immunotherapy to patients with esophageal cancer are likely to surpass other gastrointestinal tumors
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Various attempts to find breakthroughs to break the dilemma of immunological resistance Dr.
Wu Zhouqiao: In such an encouraging environment, what do you think are the current difficulties in the overall treatment of esophageal cancer? Professor Shen Lin: I think the most difficult part is still what to do if the PD-1 monoclonal antibody treatment fails.
This is a very big problem
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Although immunotherapy has made great progress, it still cannot solve all of our clinical problems.
For example, after PD-1 monoclonal antibody resistance, should we continue chemotherapy or combine targeted therapy? China has a large number of research results in basic research on esophageal cancer
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Basic research shows that pan-HER family (especially EGFR) mutations in esophageal cancer and Cyclin D1 expression are very active
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Therefore, I estimate that the precise selection of targeted drugs in the future may be inseparable from these two paths in a short period of time
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Dr.
Wu Zhouqiao: What else can we do for patients whose immunotherapy has failed? Professor Shen Lin: In the past, esophageal cancer was thought to be an immunologically indolent tumor, but this kind of argument no longer exists
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Esophageal cancer is an immune sensitive tumor like lung squamous cell carcinoma and cervical cancer
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All drugs that can improve the efficacy of immunotherapy are currently being tried in esophageal cancer, so immunotherapy for esophageal cancer will continue to develop rapidly
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If the PD-1 monoclonal antibody treatment fails, other immune drugs can be used, or combined with other drugs to overcome this resistance, such as immune combined with anti-angiogenesis therapy
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Different combinations will bring new life to patients
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In addition, there are the aforementioned targets for esophageal cancer, and some suitable targeted drugs can be tried to control the disease
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The combination of targeted drugs and immunotherapy will also be more promising in the future
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Surprising results of the "basket trial", new ideas in the era of precision treatment Dr.
Wu Zhouqiao: You also reported a targeted combined immunotherapy study on neuroendocrine tumors (NET) at this CSCO meeting.
Can you share with you What about this research? Professor Shen Lin: The biggest problem with NEN treatment is the extremely short disease control time.
The tumor will progress rapidly after the first-line treatment is about 4 months, and the second-line treatment has no good treatment methods.
Therefore, the treatment of NEN is very complicated and difficult
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For neuroendocrine tumors (NEN), small cell lung cancer is well known
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But apart from small cell lung cancer, there are no standard treatment options for other neuroendocrine cancer (NEC) treatments
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Therefore, the current NEC standard first-line treatment (VP-16+cisplatin) can only learn from small cell lung cancer
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Although there is no clinical research evidence in this regard, we have found through clinical observation that any chemotherapeutic drug has almost the same effect on NEC patients
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Because NEC is easy to be misdiagnosed, it is possible that the patient used other options first, and finally diagnosed with NEC, then the efficacy of the previous program does not seem to be significantly different from the first-line treatment (VP-16+cisplatin)
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Therefore, we have been exploring and tried many drugs, including the anti-angiogenic drug Sofatinib in this report
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In addition to anti-VEGFR and FGFR, Sofatinib can also inhibit the activation of colony stimulating factor-1 receptor (CSF-1R), and the CSF-1R pathway is related to immune regulation
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So Sofatinib has both anti-vascular effects and immune regulation effects.
We tried to combine it with the immune drug teriprizumab
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We have conducted more than a dozen cohort studies, including cholangiocarcinoma, gastric cancer, esophageal cancer, small cell lung cancer, etc.
This time we reported the results of the NEN cohort at the CSCO annual meeting innovation session and found that: Riprolizumab has an effective rate of more than 20% in the treatment of advanced NEN
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Of course, all the patients in the study are patients who have failed first-line treatment.
If the superior population is screened, the effective rate can be further improved
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Therefore, I think this combination has great application prospects in the future, and Sofantinib is safe, and it can continue to be explored in combination with other drugs
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 Expert profileProfessor Lin Lin, deputy dean of Peking University Cancer Hospital, deputy director of Beijing Institute of Cancer Prevention and Treatment, director of the Department of Digestive Oncology, director of the phase I clinical trial ward, Beijing scholar, 2019 Committee Member, Chinese Anti-Cancer Association Cancer Drug Clinical Research Professional Committee, First Chairman, Chinese Society of Clinical Oncology, Clinical Research Expert Committee, Secretary-General, Chinese Anti-Cancer Association Gastric Cancer Professional Committee, Vice-Chairman, Chinese Anti-Cancer Association Colorectal Cancer Professional Committee, Beijing Cancer Prevention and Treatment Society Council References of the Rotating Director: [1]Lin S,et al.
Abstract CT211:ORIENT-15:A randomized,multicenter,double-blind,Phase III study of sintilimab+paclitaxel and cisplatin(TP)versus placebo+TP as first- line treatment in patients with unresectable locally advanced or metastatic esophageal squamous cell carcinoma.
DOI:10.
1158/1538-7445.
AM2019-CT211 Published July 2019.
[2]Kato K,Shah MA,Enzinger P,et al.
KEYNOTE-590:Phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer.
Future Oncol.
2019 Apr;15(10):1057-1066.
doi:10.
2217/fon-2018-0609.
Epub 2019 Feb 8.
PMID:30735435.