Internal and surgical experts talk about the two major esophageal cancer results of Nawuli Ulitaba, and the heavy results of the heavy esophageal cancer are approved, looking forward to the bright prospects of immunotherapy

*For medical professionals for reading reference

The two major esophageal cancer indications in Nawuli Mipida were launched simultaneously, and the boundary of the immunotherapy of esophageal cancer is being expanded.

Tumor immunotherapy has brought new hope to patients with esophageal cancer. In recent years, breakthrough progress has been made in basic research fields and clinical treatment. In June, Nawuli Yizab was approved by two new indications of the two major esophageal cancer in China, becoming the first PD-1/PD-L1 inhibitor in China that is the only PD-1/PD-L1 inhibitors that are currently the only auxiliary therapy and advanced first-line treatment of esophageal cancer.

At the time of the recent opportunity for the listing of anti -esophageal cancer indications for anti -esophageal cancer, the "medical community" invited two authoritative experts in the internal medicine and surgery of esophageal cancer. The center of the center Yang Hong shared the hot issues, the latest progress in the field of esophageal cancer diagnosis and treatment, and the important value of immunotherapy for clinical diagnosis and treatment of patients with esophageal cancer at different stages. Together, the diagnosis and treatment of Chinese esophageal cancer has entered a new era.

1

The checkmate-648 research that treats esophageal cancer stands out, and the entire population OS benefits

Based on the excellent results of CheckMate-648 [1], the indication of the first-line treatment for the first-line therapy for advanced esophageal squamous squamous squamous carcinoma (ESCC) was approved in China. Professor Lin Yingcheng commented that in the III study of ESCC based on the inhibitors of an immunial examination point inhibitor, Checkmate-648 has many highlights compared to similar research: the largest research scale, a total of 970 patients with ESCC; the baseline of patients between the groups of patients; Balanced characteristics, high proportion of Asian populations (more than 70%), and advanced patients covering advanced patients with different diseases (including metastasis, local recurrence, remote recurrence, advanced stages of removal); Treatment (O+Y) group also obtained the overall survival period among all random patients. Therefore, it has also been approved by the US FDA this year and has become a new choice for the first -line therapy for esophageal squamous carcinoma.

The benefits of the whole population, PD-L1 positive people benefit more significantly

In terms of the main endpoints of the checkmate-648 research, PD-L1 expressing positive patients, the median general survival (OS) of Nawuli Uluming for combined chemotherapy (OS) is significantly better than the individual chemotherapy for more than half a year (15.4 months vs 9.1 months ; HR: 0.54; P <0.001). Professor Lin Yingcheng believes that the risk of death for the crowd is significantly reduced and the OS extension can be considered considerable, so it can be used as a preferred plan for PD-L1 positive first-line people.

Among all random groups, the median OS of Nawli Ulum The combined chemotherapy group reached 13.2 months, which was extended by 2.5 months (HR: 0.74, P = 0.002) compared to the therapy group (10.7 months). In this regard, Professor Lin Yingcheng also pointed out that the statistical design of the Checkmate-648 is rigorous. When the main endpoint (PD-L1-positive crowd OS) test is significantly level, the significant level of the endpoint can be inspected in order. Class error α value is controlled within 5%, and the α value is evenly distributed between multiple endpoints. Therefore, the secondary endpoint of the study (all random people OS) also have statistical effects, confirming that Nawuli Ulumab is combined with combined chemotherapy therapy The advanced ESCC in the first -tier treatment can make the OS of all crowds a significant benefit.

In terms of objective relief rate (ORR), the ORR of Nawuli Uluming combined with chemotherapy for PD-L1 positive population is 53%, and the ratio ratio (OR) ratio (OR) of the simple chemotherapy group ORR (20%) is 2.65; the treatment of all random groups The ORR is 47%, and the ORR (27%) ORR (27%) is 1.74. Professor Lin Yingcheng said that ORR is also an important reference for choosing drugs; the higher ORR improvement of Nawuli Mipida+chemotherapy has important clinical significance for ESCC first -line therapy, including reducing tumor load, alleviating difficulty swallowing difficulties, improvement The quality of life, improving the patient's treatment confidence and compliance, so that some patients with surgical patients can regain surgical opportunities.

The incidence of adverse reactions is low, and safety is controllable

In terms of security, Nawuliyu's combined chemotherapy has no new adverse reaction signal, and the incidence of potential immune-related adverse reactions (IRTRAE) in level 3-4 is ≤2%. Professor Lin Yingcheng pointed out that the FACT-E score of the Nawuli Ulum Kotherapy Group has remained stable during the 49-week treatment period, and it has a tendency to benefit from the simple chemotherapy group. Small.

2

CheckMate-577 has unique research, Nawuli Ulitaba's new pattern

In terms of the treatment of earlier esophageal cancer, early symptoms of esophageal cancer are not typical, and most of the patients have been local in the later stage. The Dutch Cross Study of the Dutch patients with advanced esophageal cancer [2], as well as the NEOCRTEC5010 research [3] led by the domestic Sun Yat -sen University Cancer Hospital, all show that the new assisted synchronous chemotherapy (NCRT)+surgery can significantly improve the efficacy than simple surgery. However, after receiving such schemes, a considerable number of patients still cannot reach the pathological relief (PCR) after surgery. The past studies have shown that their recurrence and metastasis risk is high and the lack of auxiliary treatment schemes in the past lack of evidence of benefits, especially for for the lack of evidence, especially for the lack of evidence, especially for, for the past ESCC patient. Research and design the characteristics of the times and break through the dilemma of assisting therapeutic treatment

Professor Yang Hong said that in the above background, the Checkmate-577 research launched in 2016 [4] has a unique vision and long-term planning: the research design is very suitable for the characteristics of the times at the time. Patients with lack of standard treatment for esophageal cancer, chemotherapy, and failure to reach PCR after surgery after surgery, and inspect the efficacy of the auxiliary treatment for postoperative surgery for this crowd; The foresight of the research designer has confirmed that immunotherapy is indeed very good in the field.

Research results have achieved good results, reflecting the tail effect

The main end point of the study shows that Nawuli Ulitaba can double the patient's median -free survival (DFS) to double, up to 22.4 months (11.0 months in the control group, HR 0.69, P <0.001); The bigger trend, the median DFS reached 29.7 months (the control group was 11.0 months, HR 0.61). Professor Yang Hong believes that Nawuli Ulitaba can reduce the risk of recurrence after surgery by more than 30%, and the patients with squamous carcinoma will be reduced by nearly 40%, which clarifies the significant benefit to this part of the patient.

No distant transfer survival period (DMFS) is the exploration end point of Checkmate-577. The 14-month follow-up results show that the median DMFS of Nawuli Mippitaria can reach 29.4 months (16.6 months in the control group, HR 0.71). In this regard, Professor Yang Hong said that unlike local recurrence, it is difficult to control through local means such as radiotherapy in the distance. Patients' prognosis is often worse. It is a clinical difficulty before. Immunotherapy can activate immune cells and penetrate into various target organs throughout the body, eliminate tiny sub -clinical lesions, effectively avoid recurrence of the whole body, and improve patient prognosis.

The results of the study at least 14 months showed that the HR values ​​of DFS and DMFS (0.67 and 0.71, respectively 0.67, 0.71, respectively have a trend of further decline than the first round (the first round is 0.69, 0.74, respectively). Professor Yang Hong pointed out that the phenomenon reflects the tail effect of immunotherapy; considering that the high risk period of recurrence within three years after the esophageal cancer surgery, the two groups may be further enlarged in the future with the extension of the follow -up time, and there are any For the reason, the OS of Checkmate-577 will eventually get positive results.

Safe and controllable, help high quality survival

In response to the safety of Nawulu's anti-anti-resistance therapy, Professor Yang Hong said that most of the adverse reactions of level 1-2, the overall safety and controllable, no new adverse reaction signals were found, and the drug discontinued due to adverse reactions caused the drug discontinue to stop the drug. There are also very few cases, and the proportion of patients in the Nawli Ulipipotraili group and the placebo group is 13%and 8%, respectively. For patients with poor esophageal cancer in the original quality of life, Professor Yang Hong believes that Nawli Ulitaba can obtain such tolerance data. Another great advantage of chemotherapy.

Based on the results of the CheckMate-577 research, Nawli Ulitaba also approved the first Chinese esophageal cancer auxiliary immunotherapy indication. Professor Yang Hong said that the research is a global III phase of double -blind random control research, and the level of evidence is high. Therefore, since 2021, both NCCN and CSCO guidelines are recommended to receive patients with advanced esophageal cancer patients with chemotherapy. The auxiliary treatment of Nawuoli Mipida has changed the treatment model of esophageal cancer surgery.

3

The "full coverage" mode of the digestive tract tumor in Nawuli Mipida is defined, and the research prospects of immunotherapy are unlimited

Based on Checkmate-648, Checkmate-577, and the previous checkmate-649 research, Nawli Ulito's approval of the domestic approved indications has covered postoperative adjuvant treatment of upper gastrointestinal tumors, as well as all diseases (stomach and esophagus, esophagus, esophagus pipes Advate tract tumors for the gastroesophageal connection) and pathological types (squamous carcinoma, adenocarcinoma) for advanced first -line treatment. Professor Lin Yingcheng and Professor Yang Hong said that this series of achievements marked the boundary between the immunotherapy of the upper gastrointestinal tumor is constantly being expanded, and the majority of Chinese patients will usher in more hope of improving the prognosis.

In recent years, the research of esophageal cancer immunotherapy has been in full swing, but there are still many unknown areas waiting to be explored. Professor Lin Yingcheng believes that research hotspots include seeking new immunotherapy targets, optimizing immune combination plans, and the best predictive biomarkers to determine immunotherapy. After the introduction of immunotherapy during esophageal cancer surgery, a large focus of argument in the academic community is whether the combined treatment strategy still needs to be added with radiotherapy. Professor Yang Hong insisted on the research direction to do addition. Treatment has further improved the PCR rate and seek longer survival time for patients. Expert Introduction

Professor Lin Yingcheng

Cancer Hospital of Shantou University School of Medicine

Deputy Dean, Director of the University of Science and Technology, Chief Physician

Professor, master's tutor

Deputy Chairman of the Cancer Special Committee of the Guangdong Medical Association

Deputy Chairman of the Precision Medical Committee of the Guangdong Provincial Clinical Medical Association

Vice President of Guangdong Chest Tumor Prevention Research Association

Deputy Chairman of the Cancer Rehabilitation and Passing Treatment Special Committee of the Guangdong Anti -Cancer Association

Deputy Chairman of the Cancer Prevention and Control Professional Committee of the Guangdong Provincial Health Management Society

Deputy Chairman of the Guangdong Pharmaceutical Society of Pharmaceutical Society

Deputy Chairman of the Cancer Specialist Committee of the Guangdong Medical Education Society

Executive Member of the Chinese Medical Education Society of Tumor Immunotherapy Specialty Committee

Expert Introduction

Professor Yang Hong

Chief physician, blog director, outstanding youth medical talents in Guangdong Province

Chipmodism of the Cancer Prevention and Treatment Center of Sun Yat -sen University

Deputy Director

South China Oncology Key Laboratory Independence PI

Member

Executive Member of the China Clinical Oncology Society (CSCO) Youth Expert Committee

Member of the Chinese Anti -Cancer Association esophageal cancer professional committee

Chairman of the Professional Committee of A targeted therapy of chest tumor prevention and treatment of chest tumors in Guangdong Province

Deputy Chairman of the First Cheung Surgery Expert Committee of the Guangdong Pharmaceutical Society

references:

[1] Doki Y, Ajani Ja, Kato K, et al. Nivolumab Combinationy in Advanced ESOPHAGEAL SQUAMOUS-CLL CarCinoma. N English. 2022; 386 (5): 449-462.

[2] Eyck BM, van Lanschot JJB, Hulshof MCCM, et al. Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial. J Clin Oncol. 2021;39(18):1995-2004.

[3] Yang H, Liu H, Chen Y, et al. Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: The NEOCRTEC5010 Randomized Clinical Trial. JAMA Surg. 2021;156(8) : 721-729.

[4] Kelly RJ, Ajani Ja, Kuzdzal J, et al. Adjuvant nivolumab in resed esophageal or gastroesopal junction car. N engl j Med. 2021; 384 (13): 1191-1203.

*This article is only used to provide scientific information to medical people, and does not represent the viewpoint of this platform

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