PD-1 antibody combined with chemotherapy can significantly prolong the survival time of patients with esophageal cancer

Esophageal cancer is a high-incidence tumor in China.
According to Globalcan data, in 2020, esophageal cancer ranks fifth and fourth in the number of new cases and deaths of malignant tumors in the world.
Among them, the proportion of new cases and deaths in the Chinese population Both exceed 50% of the world total [1]
.

Different from the pathological characteristics of adenocarcinoma in European and American countries, more than 90% of esophageal cancer in China is pathologically characterized as squamous cell carcinoma
.

For patients with advanced esophageal squamous cell carcinoma, the current first-line standard treatment is dual-agent chemotherapy, but chemotherapy alone is not effective, with an effective rate of about 30%, and a median survival time of less than one year [2].
It is urgent to explore for Chinese patients with esophageal cancer.
More effective treatments to prolong survival
.

Recently, the team of Professor Ruihua Xu from the Cancer Center of Sun Yat-sen University led a report on JAMA entitled Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma-The ESCORT-1st Randomized Clinical Trial The article [3] found a new treatment method for patients with advanced esophageal squamous cell carcinoma
.

It is reported that the first author of this article is Luo Huiyan, the deputy chief physician of Sun Yat-sen University Cancer Center, and Professor Xu Ruihua is the corresponding author
.

PD-1 (programmed cell death protein-1) and its ligand (PD-L1) inhibitors are a new type of immunotherapy
.

PD-1 inhibitors can bind to human PD-1 receptors and block the PD-1/PD-L1 pathway, restore the body's anti-tumor immunity, and exert a powerful anti-tumor effect
.

Studies in other cancers have shown that PD-1 inhibitors combined with chemotherapy may further improve the efficacy, but there is still a lack of corresponding evidence in esophageal squamous cell carcinoma
.

To this end, Professor Xu Ruihua from the Cancer Center of Sun Yat-sen University led a randomized, double-blind, placebo-controlled Phase III clinical study (ESCORT-1st) with 60 units including Sichuan Cancer Hospital and Harbin Medical University Cancer Hospital.
In order to evaluate the effectiveness and safety of PD-1 monoclonal antibody (carrelizumab) combined with paclitaxel and cisplatin compared with placebo combined with paclitaxel and cisplatin in the first-line treatment of advanced esophageal cancer
.

From December 3, 2018 to May 12, 2020, a total of 596 subjects were enrolled in the study.
They were randomly enrolled according to 1:1 and received PD-1 antibody combined with paclitaxel and cisplatin or placebo combined with paclitaxel and cisplatin.
Platinum treatment, receiving PD-1 antibody or placebo maintenance treatment after 6 courses, the longest time is 2 years
.

The primary endpoints of the study are progression-free survival (PFS) and overall survival (OS)
.

Secondary research endpoints include objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and safety
.

The results showed that compared with the placebo + chemotherapy group, PD-1 antibody combined with chemotherapy can significantly prolong the median survival (15.
3 months vs 12.
0 months, P=0.
001) and median progression-free survival of patients with advanced esophageal squamous cell carcinoma Period (6.
9 months vs 5.
6 months, P<0.
001) (Figure 1), improve the objective response rate (72.
1% vs 62.
1%) and the median duration of response (mDoR, 7.
0 months vs 4.
6 months), and have Good security
.

The results showed that the PD-1 antibody combined with paclitaxel and cisplatin in the first-line treatment of patients with advanced esophageal cancer can significantly prolong the progression-free survival and overall survival of patients compared with standard first-line chemotherapy
.

Figure 1: PD-L1 antibody combined chemotherapy and chemotherapy for the overall survival (A) and disease progression-free survival (B) curves of patients with esophageal squamous cell carcinoma.
In terms of safety, PD-1 antibody combined with chemotherapy is effective in combination with placebo In comparison, except for reactive cutaneous capillary hyperplasia (RECCP), the incidence of treatment-related adverse reactions (TRAE) was similar in the two groups, and most of the RECCP resolved spontaneously; TRAE occurred in the combined treatment group at ≥3 TRAE The rate is lower (63.
4% vs.
67.
7%)
.

In addition, in terms of quality of life, the overall health deterioration risk and pain of the PD-1 antibody combined chemotherapy group are lower than those of the placebo combined chemotherapy group, and the PD-1 antibody combined chemotherapy group has worsening eating conditions, difficulty swallowing saliva, and swallowing obstruction.
Decrease related
.

Therefore, patients' compliance with chemotherapy regimens may be higher
.

The ESCORT-1st study fully considered the characteristics of Chinese patients with esophageal cancer when enrolling the population.
A total of 596 patients with esophageal squamous cell carcinoma were enrolled.
As mentioned earlier, 90% of Chinese esophageal cancer patients were The clinical practice of esophageal squamous cell carcinoma in China will have more important value
.

Regarding the choice of chemotherapy regimens, the ESCORT-1st study fully considered the immune activation effects of different chemotherapy drugs, and chose a chemotherapy regimen with better synergistic effect with immunity-paclitaxel + cisplatin instead of 5-Fu + cisplatin commonly used in Europe and the United States as a control
.

The ESCORT-1st study is carried out in more than 60 centers across the country.
It is a pure Chinese clinical trial, Chinese drug and Chinese program.
From the beginning of the trial design, it has condensed the wisdom of Chinese scholars.
The final research results can also guide the clinical practice of esophageal cancer in China.

.

The study not only confirmed the effectiveness of combined immunotherapy for patients with advanced esophageal squamous cell carcinoma, but also achieved the highest effective rate (72.
1%) of the current first-line treatment.
The study added a new plan for the combined immunotherapy of esophageal cancer and rewritten the esophagus.
Cancer treatment guidelines, and pointed out the direction for the exploration of neoadjuvant treatment of esophageal cancer
.

Original link: https://jamanetwork.
com/journals/jama/article-abstract/2784143 Platemaker: 11 References 1.
Siegel RL, Miller KD, Jemal A.
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CA Cancer J Clin.
2020 Jan ;70(1):7-30.
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Pennathur A, Gibson MK, Jobe BA, Luketich JD.
Oesophageal carcinoma.
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doi:10.
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Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, Zhang Y, Zhao K, Chen Z, Gao S, Li J, Fu Z, Gu K, Liu Z, Wu L, Zhang X, Feng J, Niu Z, Ba Y, Zhang H, Liu Y, Zhang L, Min X, Huang J, Cheng Y, Wang D, Shen Y, Yang Q, Zou J, Xu RH; ESCORT-1st Investigators.
Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial.
JAMA.
2021 Sep 14;326(10): 916-925.
doi: 10.
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