Professor Xu Ruihua: Ten important advances in clinical research on digestive system tumors in 2021

In 2021, significant progress has been made in the field of digestive system tumors, especially in immunotherapy, targeted therapy, and perioperative treatment of esophageal cancer, gastric cancer, colorectal cancer and liver cancer
.

This year, Chinese original research drugs led by Chinese scholars played an increasingly important role in the international clinical research on gastrointestinal tumors
.

"NEJM Frontiers in Medicine" invited the team of Professor Xu Ruihua from the Cancer Center of Sun Yat-sen University to review the above important developments
.

"NEJM Frontiers in Medicine" is jointly created by Jiahui Medical Research and Education Group (J-Med) and "New England Journal of Medicine" (NEJM)
.

As in the past three years, we will launch an inventory of clinical research in various important disease fields one after another, so stay tuned
.

 Huiyan Luo, Mingming He, Ruihua Xu*Department of Internal Medicine, Sun Yat-sen University Cancer Center* Corresponding author 1.
Esophageal cancer From 2019 to 2020, the second-line PD-1 antibody immunotherapy for esophageal cancer has been successful, which has promoted the arrival of the era of esophageal cancer immunotherapy
.

In 2021, PD-1 antibody combined with chemotherapy has achieved a substantial breakthrough in the first-line treatment of esophageal cancer.
PD-1 monoclonal antibody second-line therapy adds new evidence.
At the same time, the amazing results of PD-1 monoclonal antibody adjuvant therapy mark the postoperative esophageal cancer Adjuvant treatment was successful for the first time
.

1.
PD-1 monoclonal antibody combined with chemotherapy first-line treatment significantly improves patient survival KEYNOTE-590 is a randomized, controlled, double-blind, global 3 Phase trial (73% of patients with esophageal squamous cell carcinoma [ESCC]) [1]
.

The first interim analysis found that compared with placebo combined with chemotherapy, pembrolizumab combined with chemotherapy (5-fluorouracil, cisplatin) first-line treatment not only significantly improved the median total PD-L1 combined with positive score (CPS) ≥ 10 ESCC patients Survival (OS, 13.
9 vs.
8.
8 months; HR, 0.
57), and significantly improved the OS of the following patients: all ESCC patients (12.
6 vs.
9.
8 months; HR, 0.
72), PD-L1 CPS ≥ 10 patients with OS ( 13.
5 vs.
9.
4 months; HR, 0.
62), all randomized patients (12.
4 vs.
9.
8 months; HR, 0.
73)
.

In terms of progression-free survival, ESCC patients (6.
3 vs.
5.
8 months; HR, 0.
65), PD-L1 CPS ≥10 patients (7.
5 vs.
5.
5 months; HR, 0.
51) and the intention-to-treat population (6.
3 vs.
5.
8) Months; HR, 0.
65) were significantly improved (see "Selected latest clinical oncology research (2021.
11.
28-2021.
12.
4)")
.

The study reached the seven common primary research endpoints, as well as the secondary endpoint, which improved the objective response rate of the intention-to-treat population (ORR, 45.
0% vs.
29.
3%)
.

The incidence of grade 3 to 4 treatment-related adverse events was similar for chemotherapy with and without pembrolizumab
.

CheckMate 648 is a global, randomized, open-label Phase 3 trial for unresectable advanced/relapsed/metastatic ESCC [2].
The results of the trial were first reported at the 2021 American Society of Clinical Oncology (ASCO) annual meeting
.

The enrolled patients were randomized to receive nivolumab combined with chemotherapy (5-fluorouracil, cisplatin), nivolumab combined with ipilimumab, and chemotherapy alone
.

The common primary endpoint is OS and PFS in patients with PD-1L CPS≥1
.

The secondary endpoints are OS, PFS, and ORR for all random populations
.

Compared with chemotherapy, the first-line treatment of nivolumab combined with chemotherapy significantly prolonged the median OS (15.
4 vs.
9.
1 months; HR, 0.
54) and PFS (6.
9 vs.
4.
4 months) of ESCC patients with PD-L1 CPS ≥ 1 ; HR, 0.
65)
.

The median OS (13.
2 vs.
10.
7 months; HR, 0.
74) and PFS (5.
8 vs.
5.
6 months; HR, 0.
81) of the intention-to-treat population also improved significantly, and the ORR increased (47.
0% vs.
27.
0%)
.

Compared with the chemotherapy group, nivolumab + ipilimumab in the dual immunization group was found in PD-L1 CPS ≥ 1% (13.
7 vs.
9.
1 months; HR, 0.
64) and the total population (12.
8 vs.
10.
7 Month; HR, 0.
78) significantly prolonged OS, but PFS was not prolonged.
The risk of early disease progression and early death in the dual-immune group is worthy of vigilance
.

China's esophageal cancer is different from Europe and the United States in terms of epidemiology, genetic background, and pathological classification (ESCC accounted for ≥90%).
New cases and deaths accounted for nearly half of the world
.

Based on the characteristics of the Chinese population of esophageal cancer, aiming to explore a treatment plan that fits the clinical practice of esophageal cancer in China, the author team led a randomized, double-blind, placebo-controlled, phase 3 ESCORT-1st trial with more than 60 centers across the country [3]
.

The study evaluated the effectiveness and safety of Chinese original PD-1 inhibitor carrelizumab combined with chemotherapy (paclitaxel + cisplatin) compared with placebo combined with chemotherapy in the first-line treatment of advanced or metastatic ESCC
.

The common primary endpoints are OS and PFS (see "Carrelizumab combined with chemotherapy improves survival outcomes in patients with metastatic esophageal cancer")
.

Compared with chemotherapy, carrelizumab combined with chemotherapy significantly prolonged OS (15.
3 vs.
12.
0 months), reduced the risk of death by 30%, and also significantly extended the median PFS (6.
9 vs.
5.
6 months) by 44 % Risk of disease progression
.

The carrelizumab combined chemotherapy group had higher ORR (72.
1% vs.
62.
1%; P=0.
009), longer duration of remission (7.
0 vs.
4.
6 months), and the safety of the two groups was similar
.

The ESCORT-1st study is the first phase 3 clinical trial for advanced ESCC first-line immunotherapy combined with chemotherapy.
It not only confirmed that carrelizumab combined with chemotherapy can significantly prolong the OS and PFS of patients, but also achieved a longer field of first-line treatment for esophageal squamous cell carcinoma.
OS and higher efficiency
.

At the 2021 European Society for Medical Oncology (ESMO) annual meeting, the author’s team released the main results of another Chinese multi-center randomized, double-blind, placebo-controlled, phase 3 trial (JUPITER-06) for advanced/metastatic ESCC for the first time [4]
.

In the first-line chemotherapy (paclitaxel + cisplatin) of ESCC patients, teriprizumab was added, and the median OS (17.
0 vs.
11.
0 months; HR, 0.
58) and PFS (5.
7 vs.
5.
5 months; HR, 0.
58) Significantly better than chemotherapy alone
.

In this study, the author’s team performed whole-exome sequencing of tissues and blood samples of the entire population enrolled, and will further explore the advantages of beneficial populations and the law of disease progression
.

ESMO 2021 also reported the results of a Chinese multi-center randomized, double-blind, placebo-controlled, phase 3 trial (ORIENT-15) led by Professor Lin Shen from Beijing Cancer Hospital for unresectable advanced/recurrent/metastatic ESCC[5]
.

In ESCC patients, the median OS of first-line chemotherapy (paclitaxel + cisplatin or 5-fluorouracil + cisplatin) combined with sintilimab (whole population, 16.
7 vs.
12.
5 months, HR, 0.
63; PD-L1 CPS≥ 10 population, 17.
2 vs.
13.
6 months, HR, 0.
64) and median PFS (whole population, 7.
2 vs.
5.
7 months, HR, 0.
56; PD-L1 CPS≥10, 8.
3 vs.
6.
4 months, HR, 0.
58 ) Were better than chemotherapy alone, and the ORR of the whole population was also better than chemotherapy alone (66.
1% vs.
45.
5%)
.

The success of studies such as KEYNOTE-590, CheckMate 648, and ESCORT-1st heralds a major change in the overall treatment pattern of esophageal cancer, prompting the NCCN 2020 and 2021 CSCO guidelines to update and incorporate new programs, making PD-1 antibody combination chemotherapy a The new standard plan for the first-line treatment of advanced esophageal cancer will advance the immunotherapy of esophageal cancer to the first-line treatment
.

2.
PD-1 monoclonal antibody second-line treatment adds new evidence from 2019 to 2020 KEYNOTE-181 [6], ATTRACTION-3 [7] and ESCORT [8] research focusing on ESCC patients in China have been successively obtained in the second-line treatment of esophageal cancer The success has promoted the arrival of the era of esophageal cancer immunotherapy.
PD-1 antibody monotherapy was immediately included in the 2019 NCCN and CSCO guidelines as a second-line treatment for esophageal cancer
.

The 2021 ASCO annual meeting released the results of a global multi-center, randomized, controlled, three-phase RATIONALE 302 trial [9]
.

The study found that tislelizumab compared with second-line single-agent chemotherapy (paclitaxel/docetaxel/irinotecan) significantly improved the median OS of the entire population of ESCC (8.
6 vs.
6.
3 months; HR, 0.
70), and significantly improved PD-L1 vision estimates the median OS (10.
3 vs.
6.
8 months; HR, 0.
54) of the population with CPS (vCPS) ≥ 10%
.

RATIONALE 302 adds new evidence to the second-line treatment of esophageal cancer with PD-1 monoclonal antibody
.

3.
PD-1 monoclonal antibody achieved breakthrough in adjuvant therapy after surgery.
CheckMate 577 is the first global, randomized, double-blind phase 3 trial that evaluates immune checkpoint inhibitors in the adjuvant treatment of esophageal cancer/GEJC after neoadjuvant chemoradiation combined with surgery [10 ]
.

The trial included the following patients: stage Ⅱ/Ⅲ GEJC adenocarcinoma or squamous cell carcinoma who had received neoadjuvant radiotherapy and chemotherapy, but had not achieved complete pathological remission [≥ypT1 or ≥ypN1]
.

These patients were randomized to receive adjuvant nivolumab or placebo after R0 surgical resection
.

The results showed that compared with placebo, nivolumab significantly improved the primary endpoint median disease-free survival (22.
4 vs.
11.
0 months), and reduced the risk of recurrence or death by 31%.
Among them, the risk of adenocarcinoma and squamous cell carcinoma were reduced respectively.
25% (95% CI, 0.
59 to 0.
96) and 39% (95% CI, 0.
42 to 0.
88)
.

OS data is not yet mature
.

There was no difference in the quality of life between the nivolumab or placebo group
.

CheckMate 577 is the first study to confirm the benefit of adjuvant immunotherapy after GEJC.
It establishes adjuvant nivolumab as the new standard treatment and marks GEJC as the second PD-1 monoclonal antibody adjuvant after melanoma The types of tumors that benefit from treatment have prompted adjuvant immunotherapy to be written into the 2020 NCCN and 2021 CSCO guidelines for esophageal cancer
.

2.
Gastric cancer In 2021, a substantial breakthrough was made in the first-line treatment of gastric cancer with immunotherapy combined with chemotherapy.
Not only did it discover a first-line treatment plan for PD-1 monoclonal antibody combined with chemotherapy that improves the survival of patients with HER2-negative gastric cancer, but also found a way to significantly improve the efficiency of patients with HER2-positive gastric cancer.
PD-1 monoclonal antibody combined with HER2 monoclonal antibody and chemotherapy as a first-line treatment plan
.

4.
PD-1 monoclonal antibody combined with chemotherapy in the first-line treatment of HER2-negative gastric cancer significantly improves patient survival.
CheckMate 649 is a PD-L1 inhibitor-based first-line treatment for unresectable advanced/recurrent/metastatic, HER2-negative gastric cancer/gastroesophageal junction cancer/ A randomized, controlled, open-label, global phase 3 trial of esophageal adenocarcinoma (GC/GEJC/EAC) (70% of gastric cancer; all tumors are adenocarcinoma) [11]
.

CheckMate 649 confirmed that in PD-L1 CPS≥5, CPS≥1 and all randomized patients, compared with first-line chemotherapy, nivolumab combined with FOLFOX or CAPE-OX as first-line treatment has better OS and PFS
.

In terms of the primary endpoint, the median OS (14.
4 vs.
11.
1 months; HR, 0.
71) and median PFS (7.
7 vs.
6.
0 months; HR, 0.
68) with PD-L1 CPS≥5 were significantly better
.

The median OS (HR, 0.
77; P<0.
0001) and PFS (HR, 0.
74) of PD-L1 CPS≥1 and the median OS (HR, 0.
80; P=0.
0002) and PFS (HR, 0.
77) of the intention-to-treat population Also improved (see "Chemotherapy combined with nivolumab as first-line treatment to improve the survival of patients with gastroesophageal adenocarcinoma")
.

The 2021 ESMO annual meeting released the results of the CheckMate 649 dual immunization group nivolumumab + ipilimumab compared with the chemotherapy group, suggesting that the dual immunization group failed to improve the median OS of patients with PD-L1 CPS ≥ 5 (11.
2 vs.
11.
6 months) or the median OS of the intent-to-treat population (11.
7 vs.
11.
8 months)
.

ORIENT-16 is a randomized, double-blind, phase 3 trial comparing Sintilimab combined with chemotherapy and chemotherapy in the first-line treatment of unresectable advanced/recurrent/metastatic, HER2-negative gastric cancer/GEJC adenocarcinoma [12], ESMO 2021 The meeting reported the results of the interim analysis for the first time
.

ORIENT-16 confirmed that in tumors expressing PD-L1 CPS ≥ 5 and all randomized patients, compared with CAPE-OX chemotherapy, sintilimab combined with CAPE-OX as a first-line treatment can significantly improve PD-L1 CPS ≥ 5 and The median OS of all randomized patients (PD-L1 CPS≥5, 18.
4 vs.
12.
9 months, HR, 0.
66; all patients, 15.
2 vs.
12.
3 months, HR, 0.
77)
.

OS benefit was observed in all pre-determined PD-L1 CPS subgroups
.

Sintilimab combined with CAPE-OX also significantly improved PFS (HR of PD-L1 CPS≥5, 0.
63; HR of all randomized patients, 0.
64), and the ORR of all randomized patients was significantly improved (58.
2% vs.
48.
4%)
.

In the context of previous studies such as KEYNOTE-062 [13] and ATTRACTION-4 [14] that failed to confirm the benefit of OS, CheckMate 649 conducted in the Chinese population was the first to prove that PD-1 monoclonal antibody combined with chemotherapy is better than first-line chemotherapy alone.
Significantly improve the survival of HER2-negative advanced GC/GEJC/EAC Phase 3 trial, the patient's OS has a milestone improvement, which prompted the U.
S.
Food and Drug Administration (FDA) to approve nivolumab combined with FOLFOX or CAPE-OX in 2021 First-line treatment for HER2-negative GC/GEJC/EAC, and written into the 2021 NCCN and CSCO gastric cancer guidelines, establishes this therapy as the new standard treatment for HER2-negative advanced GC/GEJC/EAC
.

5.
PD-1 monoclonal antibody combined with anti-HER2 therapy and chemotherapy as the first-line treatment of HER2-positive gastric cancer significantly improves the effective rate KEYNOTE-811 is the first to add PD to the first-line anti-HER2 combination chemotherapy for HER2-positive, unresectable or metastatic gastric cancer/GEJC patients -1 A global, randomized, double-blind, placebo-controlled phase 3 trial of mAb [15]
.

The 2021 ASCO annual meeting released the results of its first interim analysis, suggesting that pembrolizumab + trastuzumab + chemotherapy (5-fluorouracil + cisplatin or capecitabine + oxaliplatin) is better than placebo + trastuzumab Mab + chemotherapy as the first-line treatment significantly improved ORR (74.
4% vs.
51.
9%), the complete remission rate of pembrolizumab group was close to 4 times that of placebo group (11.
3% vs.
3.
1%), pembrolizumab group The proportion of remission duration ≥ 6 months and ≥ 9 months was higher than that of the placebo group (70.
3% vs.
61.
4%, 58.
4% vs.
51.
1%, respectively)
.

The incidence of adverse events was similar between the two groups
.

The results of PFS and OS are not yet mature
.

In December 2021, Nature published the above results [16], and suggested that the pembrolizumab group had a deeper tumor response than the placebo group (median tumor shrinkage from baseline, -65% vs.
-49%; The proportions with a degree of shrinkage greater than 80% from the baseline were 32.
3% vs.
14.
8%) (see "Double Blocking Leading Role | Selected Latest Clinical Oncology Literature (12.
19-25)")
.

Based on the amazing ORR data of KEYNOTE-811, the FDA has approved pembrolizumab combined with trastuzumab and chemotherapy for the first-line treatment of HER2-positive gastric cancer/GEJC in 2021, and will be included in the 2021 NCCN gastric and esophageal cancer guidelines
.

3.
Colorectal cancer In 2021, the major progress of immunotherapy for colorectal cancer is still limited to MSI-H/dMMR colorectal cancer, and immune monotherapy has shown consistent advantages and moved forward to become the first line of MSI-H/dMMR colorectal cancer.
The new standard of treatment
.

At the same time, preoperative neoadjuvant treatment of locally advanced rectal cancer adds new evidence, and the first effective anti-HER2 antibody conjugate drug appears in the field of HER2-positive refractory colorectal cancer
.

6.
PD-1 monoclonal antibody first-line treatment of MSI-H/dMMR colorectal cancer KEYNOTE-177 is the first to evaluate pembrolizumab single-agent versus standard therapy (FOLFOX or FOLFIRI chemotherapy ± bevacizumab or cetuximab Monoclonal antibody) Phase 3 clinical trials for the first-line treatment of MSI-H/dMMR metastatic colorectal cancer [17], the primary endpoints are OS and PFS (see "New England Journal of Medicine: Pembrolizumab in MSI-H/dMMR The first-line treatment of colorectal cancer beats chemotherapy ± targeted therapy")
.

The final OS analysis result of the KEYNOTE-177 study was announced at the 2021 ASCO-GI meeting in the form of an oral report [18].
The median OS of the pembrolizumab group has not yet reached, and the median OS of the standard treatment group is 36.
7 months
.

Pembrolizumab showed a trend toward a reduced risk of death compared with standard treatment (HR, 0.
74; 95% CI, 0.
53 to 1.
03; P=0.
0359), but it did not reach a statistically significant difference (preset statistically significant P value of 0.
0246 ), this may be related to the crossover to the pembrolizumab group after 60% of patients in the standard treatment group have disease progression
.

The pembrolizumab group showed a trend of OS benefit, the 36-month OS rate was 61%, and the standard treatment group was 50%
.

The second interim analysis in 2020 has revealed that the PFS of the pembrolizumab group is better than the standard treatment.
The final analysis shows that the median PFS of the pembrolizumab group is twice that of the standard treatment group (16.
5 vs.
8.
2 Month; HR, 0.
59)
.

The final ORR of pembrolizumab and standard treatment were 45.
1% vs.
33.
1%, and the adverse events related to treatment ≥3 were 21.
6% vs.
66.
4%, respectively
.

KEYNOTE-177 was not only written into the 2020 NCCN Colorectal Cancer Guidelines based on the PFS results of the second interim analysis, but also received the level I recommendation of the 2021 CSCO Colorectal Cancer Guidelines
.

Pembrolizumab has become the new standard for the first-line treatment of unresectable or metastatic MSI-H/dMMR colorectal cancer
.

7.
Neoadjuvant therapy can improve the pathological complete remission rate and disease-free survival rate of rectal cancer.
Preoperative radiochemotherapy, total mesorectal resection and adjuvant chemotherapy are the standard treatments for locally advanced rectal cancer
.

UNICANCER-PRODIGE 23 is an open-label, randomized, multi-center phase 3 trial that compares neoadjuvant therapy and standard therapy for locally advanced rectal cancer (cT3-4M0) in France [19].
The neoadjuvant therapy group includes 6 cycles of FOLFIRINOX , And subsequent capecitabine/radiotherapy, surgery, and 3-month modified FOLFOX6 or capecitabine adjuvant treatment; standard treatment includes preoperative capecitabine/radiotherapy, surgery and 6-month adjuvant chemotherapy (FOLFOX or card Peitabine) (see "The whole course of neoadjuvant therapy improves the remission rate and survival rate of patients with rectal cancer")
.

The results found that in terms of the primary endpoint, the 3-year disease-free survival rate of neoadjuvant therapy was better than standard treatment (76% vs.
69%; HR, 0.
69; P=0.
034), and the 3-year metastasis-free survival rate was also better than the latter (79% vs.
72%)
.

The 3-year OS rate was similar in the two groups
.

The pathological complete remission rate was higher in the neoadjuvant treatment group (28% vs.
12%), and the pN0 rate was also higher (83% vs.
67%)
.

The ratio of R0 resection was similar to that of combined abdominal-perineum resection in the two groups, and the incidence of adverse events was also similar
.

UNICANCER-PRODIGE 23 adds new evidence to the ever-increasing evidence, proving that neoadjuvant therapy is feasible for locally advanced rectal cancer, can improve the pathological remission of patients and the 3-year disease-free survival rate, and may increase the possibility of relieving patients with organ preservation Sex
.

The unresolved issues include the best neoadjuvant chemotherapy regimen, whether chemotherapy should be given first or radiochemotherapy, and the role of short-term radiotherapy
.

8.
Anti-HER2-antibody conjugate drugs are expected to treat HER2-positive refractory colorectal cancer in the future.
Previous HERACLES-A [20] and MyPathway [21] studies have shown that trastuzumab combined with lapatinib or Pertuzumab The ORR of anti-HER2-positive, metastatic colorectal cancer posterior line treatment is 30%-40%, so anti-HER2 dual-targeted combination therapy is included in the NCCN and CSCO guidelines as a posterior-line treatment option for HER2-positive, metastatic colorectal cancer
.

The anti-HER2-antibody conjugate drug trastuzumab-deruxtecan (T-DXd, DS-8201) is a humanized anti-HER2 monoclonal antibody trastuzumab, topoisomerase I inhibitor DXd and An antibody-drug conjugate composed of a tetrapeptide-based cleavable linker has been approved by the FDA for the subsequent treatment of HER2-positive gastric cancer (DESTINY-GASTRIC01 [22], the ORR of T-DXd vs.
chemotherapy is 51, respectively % vs.
14%)
.

DESTINY-CRC01 is an open-label, international multicenter, phase 2 trial that evaluates T-DXd as a single agent as a third-line and above treatment for HER2-positive metastatic colorectal cancer [23], which includes HER2-positive, IHC2+/ISH− and There are 3 cohorts in IHC1+
.

The HER2-positive cohort (IHC3+ or IHC2+/ISH+) had a confirmed ORR (primary endpoint) of 45.
3%, and the ORR of patients who had received and had not received HER2-targeted therapy was similar (43.
8% vs.
45.
9%), but had not received HER2 The median PFS of targeted therapy patients exceeded that of treated patients (6.
9 vs.
4.
3 months)
.

The median OS has not yet been reached
.

The ORR of IHC3+ patients was higher than that of IHC2+/ISH+ patients (57.
5% vs.
7.
7%)
.

Patients in the other two cohorts did not see any remission
.

Interstitial lung disease or pneumonia occurred in 6% of patients
.

T-DXd is the first anti-HER2 antibody-conjugate drug to show anti-tumor activity in patients with HER2-positive and metastatic colorectal cancer.
Drug standard treatment
.

IV.
Liver cancer immunotherapy (PD-1 monoclonal antibody) combined with small molecule anti-vascular targeted drugs (regorafenib or furquetinib) has been explored in the field of MSS/MSI-L/pMMR refractory colorectal cancer , Phase 1/2 trials have initially shown an efficacy of 15% to 36% [24-26], but in 2021, PD-1 monoclonal antibody + VEGF monoclonal antibody has shown more obvious and precise results in the first-line treatment of liver cancer.
Benefit
.

9.
The first-line treatment of PD-1 monoclonal antibody combined with VEGF monoclonal antibody significantly improved the survival of patients with liver cancer.
/ A randomized, open-label, Chinese multi-center phase 2/3 clinical trial of metastatic HBV-related hepatocellular carcinoma [27]
.

The single-arm phase 2 trial of sintilimab combined with IBI305 used safety as the primary endpoint, and the incidence of treatment-related adverse events at grade 3 and above was 29%
.

The phase 3 randomized controlled trial took OS and PFS in the intention-to-treat population as the common primary endpoints.
Sintilimab combined with IBI305 compared with sorafenib significantly prolonged the median PFS (4.
6 vs.
2.
8 months; HR, 0.
56) and the first intermediate The analyzed median OS (not reached vs.
10.
4 months; HR, 0.
57), and significantly improved ORR (21% vs.
7%)
.

The incidence of common 3-4 treatment-related adverse events in the two groups was 14% vs.
6%, and the incidence of hand-foot syndrome was 0% vs.
12%
.

Based on the ORIENT-32 study, Sintilizumab combined with bevacizumab has been approved by the National Medical Products Administration (NMPA) for first-line treatment of liver cancer in 2021, and is the world's first approved first-line treatment for liver cancer PD-1 monoclonal antibody + anti-angiogenic monoclonal antibody combination therapy
.

10.
PD-L1 monoclonal antibody combined with VEGF monoclonal antibody in the first-line treatment of liver cancer results update IMbrave150 confirmed that atilizumab combined with bevacizumab versus sorafenib in the first-line treatment of unresectable/metastatic hepatocellular carcinoma (Child-Pugh A ) Significantly improved the common primary endpoint OS (not reached vs.
13.
2 months; HR, 0.
58) and median PFS (6.
8 vs.
4.
3 months; HR, 0.
59) [28], and significantly improved ORR (27.
3% vs.
11.
9) %)
.

The deterioration of quality of life of atilizumab combined with bevacizumab was also later than that in the sorafenib group (11.
2 vs.
3.
6 months; HR, 0.
63), but the incidence of adverse events above grade 3 was higher (38.
0) % vs.
30.
8%) (see "The standard treatment of liver cancer has not changed for 13 years, now it can finally be upgraded")
.

The 2021 ASCO-GI meeting updated the OS results of IMbrave150 [29]: Atelizumab combined with bevacizumab versus sorafenib continued to show a median OS benefit (19.
2 vs.
13.
4 months; HR, 0.
66 ; P=0.
0009), the updated ORR was 29.
8% vs.
11.
3%, and more patients achieved complete remission (7.
7% vs.
0.
6%)
.

IMbrave150 is a landmark trial that establishes a new standard for first-line treatment.
It is the first to prove that the outcome of hepatocellular carcinoma patients receiving PD-L1 monoclonal antibody combined with VEGF monoclonal antibody treatment is better than that of sorafenib treatment
.

Atelizumab combined with bevacizumab has been approved by the FDA as the world's first first-line immunotherapy combination therapy for liver cancer, and has been included in the NCCN and CSCO guidelines
.

Expert introduction Xu Ruihua, Doctor of Medicine, Chief Physician, Professor, Doctoral Supervisor, Director, Dean, and Research Institute Director of Sun Yat-Sen University Cancer Center, Director of the State Key Laboratory of Oncology in South China, Director of the Collaborative Innovation Center of the Ministry of Cancer Medicine , Director of the National Center for Clinical Trials of New Drugs (Anti-tumor Drugs), selected into the National Hundreds and Thousands of Talents Project, and an expert with special government allowances from the State Council
.

He is currently the chairman of the Chinese Society of Clinical Oncology (CSCO), the chairman of the Chinese Anti-Cancer Association, and the editor-in-chief of Cancer Communications
.

He has long been engaged in gastrointestinal tumor diagnosis, individualized treatment and translational research, and has achieved internationally advanced and innovative results in early diagnosis and immunotherapy.
He has published more than 300 papers and published papers in important international academic journals as a correspondence/first author 199 articles, such as JAMA, Nature Materials, Nature Medicine, Lancet Oncology, Journal of Clinical Oncology, JAMA Oncology, Annals of Oncology, etc.
, won 2 second prizes of National Science and Technology Progress Award (first completion person) and China Medical Science and Technology Award and other provinces 6 ministerial first prizes
.

Luo Huiyan, Ph.
D.
, Deputy Chief Physician, Master's Supervisor, Deputy Chairman of the Youth Committee of the Gastric Cancer Professional Committee of the Chinese Anti-Cancer Association, Member and Secretary of the Standing Committee of the Professional Committee of Cancer Targeted Therapy of Guangdong Anti-Cancer Association
.

Mainly engaged in the diagnosis, individualized treatment and translational research of gastrointestinal tumors
.

As the main researcher, he presided over or participated in a number of scientific research projects such as national key research and development projects and national natural science fund projects, and participated in and completed more than 100 international and domestic multi-center clinical trials
.

He has published more than 100 papers in domestic and foreign journals, and has published more than 20 papers in JAMA, Nature Materials, Lancet Oncology, Science Translational Medicine, Annals of Oncology, PNAS, Clinical Cancer Research, etc.
as the first/co-author
.

The results of the two studies were adopted by NCCN guidelines in the United States, rewriting the global diagnosis and treatment model
.

As the third participant, he won one second prize of National Science and Technology Progress Award
.

He Mingming, Doctor of Medicine, Postdoctoral Fellow at Harvard University, Attending Physician, Master Supervisor, Member of the Professional Committee of Targeted Tumor Therapy of Guangdong Anti-Cancer Association
.

Mainly engaged in the diagnosis, individualized treatment and translational research of gastrointestinal tumors
.

First / co-author in a JAMA Oncology, Cell Reports Medicine, JNCCN , International Journal of Cancer, Cancer Science and other journals published more than 10 papers
.

Responsible for completing a number of clinical trials, and the results will be exhibited at ASCO, ESMO, ESMO-GI conferences or oral reports
.

Participate in or preside over the national key research and development projects, the National Natural Science Foundation of China, the Guangdong Natural Science Foundation, the provincial and ministerial Guangzhou Science and Technology Plan, the CSCO Hisco Foundation, the 5010 conventional project of Sun Yat-Sen University and other scientific research projects
.

The results of a study were cited by the Canadian Current Oncology Practice Guideline
.

Reference 1.
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