Bai Li: Blockbuster research, authoritative guideline recommendation, overview of the current path of upper gastrointestinal tumor immunotherapy

Editor's note

Since the advent of immunotherapy, great progress has been made in different cancers, changing the treatment landscape
of multiple tumors.
In the past decade, when we talk about the progress of cancer treatment, it is difficult not to mention the outstanding contribution
of "immunotherapy" to human anti-cancer.
In recent years, breakthroughs and advances in immunotherapy in the field of upper gastrointestinal tumors have also continued to surprise
us.
From late posterior line to late first-line, and then to perioperative adjuvant therapy, with the accumulation of more blockbuster research data, nivolumab-based immunotherapy has created a new situation
in the "three-whole era" of upper gastrointestinal tumor immunotherapy, that is, all positions (esophageal cancer, gastric cancer), all types (squamous cell carcinoma, adenocarcinoma), and the whole course (perioperative, first-line, posterior line).

To this end, this issue of "Physician Daily" invites Professor Bai Li of the General Hospital of the Chinese People's Liberation Army to review the breakthroughs and progress of upper gastrointestinal immunotherapy, and review the development of immunotherapy in different fields of upper gastrointestinal tumors with her years of experience and ideas, so as to record the process of immunotherapy entering upper gastrointestinal tumors and how it helps us truly overcome the ultimate human problem of cancer, and look forward to the bright vision
of future immunotherapy development.

The Doctor

Physician's Daily: In recent years, what are the latest clinical advances and breakthroughs in treatment methods in the field of upper gastrointestinal tumors?

    Professor Baili

Upper gastrointestinal tumors usually refer to tumors
that occur in the esophagus, the esophageal gastric junction and the stomach.
China is a large country of esophageal cancer, accounting for more than 50% of the world's total, of which more than 90% of patients belong to squamous cell carcinoma, while foreign esophageal cancer is mainly
adenocarcinoma.

For drug treatment, there has been no major breakthrough and progress in chemotherapy, and the progress of new drug research and development is mainly concentrated in three types of drugs: the first is targeted drugs
.
Compared with the continuous breakthroughs in innovative treatments for non-small cell lung cancer such as KRAS G12C, IDH1 for biliary tract tumors and glioblastoma, and FGFR2 fusion genes, the targeted diagnosis and treatment of upper gastrointestinal tumors is booming, but the results are minimal, and the drugs currently on the market are mainly HER2-targeted.
The second class is ADC drugs, which are the most developed and successful in solid tumors and also target HER2 targets; The third category is immunotherapy drugs
that have brought earth-shaking changes to the treatment of upper gastrointestinal tumors.
In esophageal squamous cell carcinoma, immunotherapy has achieved full line coverage from the back line to the first line to the perioperative period, in addition to imported immunotherapy drugs such as nivolumab and pembrolizumab, domestic immunotherapy drugs have also carried out many related studies and achieved consistent benefits
.
Among them, CheckMate577 has made great breakthroughs and progress
in immunomonotherapy adjuvant therapy for patients with residual postoperative surgery after neoadjuvant chemoradiotherapy for esophageal cancer.

At present, immunotherapy is still controversial
in adenocarcinoma of the esophagogastric junction, esophageal adenocarcinoma and gastric cancer.
The KEYNOTE-062 study failed, while the CheckMate-649 study and the ORIENT16 study yielded better data
.
The results of second-line immunotherapy for gastric cancer are unsatisfactory and are still blank, but it is not ruled out that there is still room for progress, such as in combination
with second-line standard chemotherapy or antivascular drugs.

The Doctor

Q: What are the recommendations of the latest CSCO guidelines and NCCN guidelines for immunotherapy for esophageal cancer?

    Professor Baili

In the field of esophageal cancer, the recommended level of immunotherapy is relatively high
in authoritative guidelines at home and abroad.
First of all, for patients with resectable esophageal cancer, based on the dazzling data of the CheckMate577 study, the NCCN guideline and CSCO guideline for postoperative nivolumab immunoadjuvant therapy are recommended
by category 1 evidence.
Neoadjuvant immunotherapy is in the research stage, and the results announced are all phase I~II.
studies, which still need to be further verified
by large phase III clinical studies.
NCCN guidelines do not recommend
neoadjuvant immunotherapy.
Based on a large number of domestic neoadjuvant immunotherapy results and combined with clinical practice, the CSCO guideline recommends neoadjuvant immunotherapy combined with chemotherapy as a grade III for patients with resectable thoracic esophageal cancer in
any N stage of cT1b~cT2 N+ or cT3~cT4a.

For patients with unresectable locally advanced or advanced esophageal cancer, immunotherapy is clearly recommended
for both posterior and first-line therapy.
Immunotherapy combination chemotherapy has become the latest first-line standard treatment for
esophageal cancer.
Based on the CheckMate648 study, NCCN guidelines recommend nivolumab plus fluorouracil and platinum-based chemotherapy (2B) as the preferred regimen for HER2-negative first-line treatment of esophageal squamous cell carcinoma Class recommendation).

HER2-negative esophageal adenocarcinoma, referring to the CheckMate649 study, nivolumab combined with fluorouracil and oxaliplatin-based chemotherapy regimen was approved for the first-line treatment of advanced or metastatic esophageal adenocarcinoma and esophagogastric junction cancer, and was not subject to it PD-L1 expression restriction, in which patients with PD-L1 CPS≥5 recommended grade I evidence, PD-L1 CPS<</b123> category patients with 10 class 10 Class

The 2022 CSCO guidelines are also based on these phase III studies in China, recommending the combination of carrelizumab, sindilimab and trepilimab as first-line treatment
for esophageal squamous cell carcinoma, respectively.
In the second- and posterior line treatment of esophageal cancer, nivolumab is recommended as category 1 evidence, and pembrolizumab is recommended for patients with esophageal squamous cell carcinoma (type 1 evidence) or MSI-H/dMMR and TMB-H esophageal cancer in
patients with PD-L1 CPS≥10.

The Doctor

Q: Could you please introduce the important clinical value of nivolumab in the adjuvant therapy of esophageal cancer after surgery and the treatment of advanced esophageal cancer?

    Professor Baili