[ESMO2021] A number of studies on gastrointestinal tumors bring new standard programs to China!

*Only for medical professionals to read and refer to the frontier progress of ESMO digestive tract tumors, bringing you new thinking
.

The 2021 European Society of Medical Oncology (ESMO) conference will be held online from September 16th to 21st
.

As the most prestigious and influential oncology conference in Europe, ESMO has become a global academic exchange platform that integrates clinical practice, translational research and interdisciplinary discussions
.

Affected by the global epidemic this year, oncologists and scholars from all over the world gathered in the cloud to share the latest research progress in the field of tumor therapy
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At this ESMO conference, a number of studies have brought new treatment options for gastrointestinal cancers (gastric cancer, esophageal cancer, and cholangiocarcinoma) in China
.

These included two important conference oral reports-a phase III clinical study of sintilimab combined with chemotherapy in the first-line treatment of advanced gastric cancer and esophageal squamous cell carcinoma, and a poster presentation of a phase II study of pemigatinib in the treatment of advanced cholangiocarcinoma in China
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 ORIENT-16 study: Sintilimab combined with chemotherapy significantly prolonged the OS of the overall population of gastric cancer, bringing a new standard for the first-line treatment of advanced gastric cancer in China! ORIENT-16 is a comparison of Sintilimab injection combined with chemotherapy (oxaliplatin + capecitabine) or placebo combined with chemotherapy (oxaliplatin + capecitabine), first-line treatment of unresectable local A randomized, double-blind, multi-center, phase III study of the effectiveness and safety of advanced, recurrent or metastatic gastric and gastroesophageal junction adenocarcinoma
.

Professor Xu Jianming from the Fifth Medical Center of the General Hospital of the People’s Liberation Army reported the interim analysis on behalf of the Chinese research team [1] Results: The study reached all the research endpoints, significantly prolonging the overall survival (OS) of the overall population and the OS of the PD-L1 positive population
.

The ORIENT-16 study became the first phase III clinical study in China that confirmed that PD-1 inhibitors combined with chemotherapy as the first-line treatment of advanced gastric cancer significantly prolonged survival in the overall population
.

Professor Xu Jianming ORIENT-16 oral report The ORIENT-16 study design is specially designed for Chinese gastric cancer patients: double-blind study design, non-open labeling, to avoid result deviation; 6 cycles of Sintilimab or placebo combined with oxaliplatin After tabine, use Sintilimab or placebo combined with capecitabine for maintenance, improve treatment compliance, and reduce chemotherapy toxicity; the main research endpoint is OS for the entire population of gastric cancer and OS for people with CPS≥5
.

The ORIENT-16 study design study showed that compared with chemotherapy, sintilimab combined with chemotherapy significantly reduced the risk of death in the overall population (HR 0.
766, 95% CI: 0.
626-0.
936, p=0.
0090) and death in people with CPS ≥ 5 Risk (HR 0.
660, 95%CI: 0.
505-0.
864, p=0.
0023), reaching the preset double superiority standard; median OS was extended by 2.
9 months in the overall population (median OS 15.
2 months vs.
12.
3 months), In the population with CPS ≥ 5, the extension was 5.
5 months (median OS 18.
4 months vs.
12.
9 months)
.

Moreover, OS has the same trend of benefit in all the pre-specified subgroup analyses
.

ORIENT-16 study OS results ORIENT-16 study OS subgroup analysis (overall population) Similarly, compared with chemotherapy, sintilimab combined with chemotherapy significantly reduced the overall population (HR 0.
636, 95%CI: 0.
525-0.
771, p< 0.
0001) and the population with CPS ≥ 5 (HR 0.
628, 95% CI: 0.
489-0.
805, P=0.
0002); the median progression-free survival (PFS) was extended by 1.
9 months in the population with CPS ≥ 5 (median PFS) 7.
7 months vs.
5.
8 months), the overall population was extended by 1.
4 months (median PFS 7.
1 months vs.
5.
7 months)
.

ORIENT-16 study PFS results The objective response rate (ORR: 58.
2% vs.
48.
4%) of the sintilimab combined with chemotherapy group was higher than that of the chemotherapy group, and the median duration of response (mDOR: 9.
8 months vs.
7.
0 cases) Months) longer
.

The safety characteristics are consistent with previously reported clinical research results related to Sintilimab, and there is no new safety signal
.

The results of this study show that for the first-line treatment of Chinese gastric cancer patients, regardless of the expression of PD-L1, sintilimab combined with chemotherapy can significantly prolong OS and PFS compared with chemotherapy alone, providing a new standard first-line for Chinese gastric cancer patients Treatment plan
.

 ORIENT-15 Research: Another City! For patients with advanced esophageal squamous cell carcinoma, Sintilimab combined with chemotherapy significantly prolonged OSORIENT-15 is a comparison between Sintilimab combined chemotherapy (cisplatin + paclitaxel/5-fluorouracil) and placebo combined chemotherapy (cisplatin + paclitaxel/ 5-Fluorouracil) A randomized, double-blind, international multi-center phase III study in the first-line treatment of patients with unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma
.

Professor Lin Shen from Peking University Cancer Hospital reported the interim analysis on behalf of the international research team at this ESMO conference [2] Results: Reached all the research endpoints, significantly prolonged the OS of the overall population and the OS of the PD-L1 positive population
.

This is the first international multi-center study in the field of esophageal cancer treatment led by Chinese experts in first-line immunotherapy
.

Professor Lin Lin ORIENT-15 oral report In the overall population, the sintilimab combined with chemotherapy group significantly prolonged the median OS compared with the chemotherapy group.
The median OS of the two groups was 16.
7 months and 12.
5 months, respectively, which significantly reduced the risk of death 37.
2%, the hazard ratio (HR) is 0.
628
.

In the PD-L1 positive (CPS≥10) population, sintilimab combined with chemotherapy also significantly prolonged the median OS compared with placebo combined with chemotherapy.
The median OS of the two groups was 17.
2 months and 13.
6 months, respectively, reducing deaths The risk is 36.
2%, HR is 0.
638, p=0.
0018
.

Moreover, consistent OS benefits were observed in all pre-specified subgroup analyses
.

ORIENT-15 study OS results ORIENT-16 study OS subgroup analysis (general population) Sintilimab combined with chemotherapy group also observed a significant prolongation of median PFS
.

In the overall population, the median PFS of the two groups were 7.
2 months and 5.
7 months, respectively, and the HR was 0.
558, p<0.
0001; in the PD-L1 positive (CPS≥10) population, the median PFS of the two groups were 8.
3 months and 6.
4 months, HR was 0.
580, p<0.
0001
.

ORIENT-15 study PFS results In addition, in the overall population and PD-L1 positive (CPS≥10) population, sintilimab combined with chemotherapy has significantly improved ORR and DOR compared to chemotherapy
.

Sintilimab combined with chemotherapy has good safety and tolerability, and no new safety signals have been seen
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The results of the study showed that in the first-line treatment of patients with unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma, regardless of the expression of PD-L1, sintilimab combined with chemotherapy significantly improved OS and PFS
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Sintilimab combined with chemotherapy provides a better first-line treatment plan for these patients
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 Pemigatinib: 100% disease control rate, new hope for the second-line treatment of patients with advanced cholangiocarcinoma in China, a poster study brought by Professor Shi Guoming from Zhongshan Hospital of Fudan University [3] showed a phase II study of pemigatinib in the second-line treatment of advanced cholangiocarcinoma in China Result
.

This study is a phase II, open, single-arm, multicenter, evaluation of pemigatinib in advanced Chinese patients who have previously received at least one systemic treatment failure, fibroblast growth factor receptor 2 (FGFR2) gene fusion or rearrangement positive The study of efficacy and safety in patients with cholangiocarcinoma is the domestic bridging test of FIGHT-202 study (INCB 54828-202, NCT02924376)
.

Intrahepatic cholangiocarcinoma is the second most common primary liver cancer.
For patients with advanced intrahepatic cholangiocarcinoma, the preferred first-line treatment is gemcitabine combined with cisplatin, etc.
The ORR is 26%, and the median OS is about 11.
7 months.
The treatment effect Limited
.

At present, patients who have failed the first-line treatment in China recommend active symptom control + mFOLFOX regimen for treatment.
The median OS is only 5-6 months.
It is urgent to see the emergence of drugs that can improve the quality of life and efficacy of patients
.

The FGFR2 gene translocation to form a fusion gene is the most common FGFR mutation in intrahepatic cholangiocarcinoma
.

Pemigatinib is a potent and selective inhibitor of FGFR subtype 1/2/3.
For patients with FGFR2 fusion or rearrangement, foreign studies have proven its effectiveness and safety
.

As of January 29, 2021, the first part is a PK study in the Chinese population, including a total of 3 cholangiocarcinoma subjects; the second part includes a total of 31 cholangiocarcinoma subjects with positive FGFR2 gene fusion or rearrangement.
According to one treatment cycle every 3 weeks (medication for two weeks, one week off) oral 9mg (first part) or 13.
5mg (part II) of pemigatinib, until disease progression, unacceptable toxicity or withdrawal of informed consent and so on
.

The primary endpoint of the clinical trial was that the 31 subjects included in the second part of the study reached the ORR assessed by the Independent Imaging Evaluation Committee (IRRC) based on the RECIST v1.
1 standard
.

The results of the study showed that in the second part of the study, among the 30 curative effect evaluable groups (1 subject was excluded from the curative effect evaluable group because the central laboratory found that the FGFR gene mutation abundance did not meet the inclusion criteria), 15 Patients achieved disease remission confirmed by IRRC, and the primary endpoint ORR reached 50% (95%CI: 31.
3%-68.
7%)
.

At a median follow-up of 5.
13 months, 12 patients were still in remission, the median DOR had not yet reached (95%CI: 3.
4-NR), the median PFS was 6.
3 months (95%CI: 4.
9-NR), disease control The DCR is 100% (95%CI: 88.
4%-100%)
.

In addition, pemigatinib is safe
.

The safety analysis included all 34 patients.
As of the data cutoff date, each subject had reported at least one treatment-related adverse event (TRAE).
The most common TRAE was hyperphosphatemia (73.
5%) and xerostomia.
(55.
9%) and alopecia (50.
0%), the incidence of TRAE ≥ grade 3 was 14.
7%
.

There were no adverse events leading to death and treatment termination during the trial
.

The results of the study suggest that pemigatinib is an efficient and tolerable second-line treatment option for Chinese patients with recurrent or metastatic cholangiocarcinoma who are positive for FGFR2 gene fusion or rearrangement
.

Summary: China is a country with a high incidence of gastrointestinal tumors.
Gastric cancer, esophageal cancer and hepatobiliary tumors are among the forefront of malignant tumors
.

In the summary and discussion session of the digestive tract cancer treatment special session at the ESMO Conference in 2021, Professor Yelena Y.
Janjigian, Director of the Digestive Tumor Treatment Center at Memorial Sloan Kettering Cancer Center in New York, commented: About Sintilimab Two large-scale phase III clinical studies, the implementation and results of the entire study are impressive, laying the important position of sintilimab combined with chemotherapy in the first-line treatment
.

ORIENT-15's research results will also change her clinical practice in the United States, making her think about using PD-1 inhibitors combined with cisplatin + paclitaxel as the first-line standard treatment for advanced esophageal squamous cell carcinoma
.

Sintilimab combined with chemotherapy in the ORIENT-16 study for the first-line treatment of advanced gastric cancer and the ORIENT-15 study for the first-line treatment of esophageal squamous cell carcinoma both obtained positive results, significantly prolonging OS, and brought new standard first-line treatment options for such patients
.

At the same time, pemigatinib, as the first targeted drug for cholangiocarcinoma, has been approved for marketing in the United States, Europe and Taiwan, China, and the application for marketing in China has been accepted by the National Medical Products Administration (NMPA)
.

In this phase II study in the Chinese population of advanced cholangiocarcinoma, the DCR is as high as 100%, the ORR is 50%, and the safety is good.
In the near future, it will provide a new plan for the second-line treatment of domestic cholangiocarcinoma patients
.

Reference materials: [1]J.
Xu,H.
Jiang,Y.
Pan,et al.
Sintilimab plus chemotherapy(chemo)versus chemo as first-line treatment for advanced gastric or gastroesophageal junction(G/GEJ)adenocarcinoma(ORIENT-16 ):First results of a randomized,double-blind,phase III study.
ESMO 2021,LBA53.
[2]L.
Shen,Z.
Lu,J.
Wang,et al.
Sintilimab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced or metastatic esophageal squamous cell cancer:First results of the phase III ORIENT-15 study.
ESMO 2021,LBA52.
[3]G.
Shi,X.
Huang,T.
Wen,et al.
Efficacy and safety of pemigatinib in Chinese patients with unresectable, advanced/recurrent or metastatic intrahepatic cholangiocarcinoma with FGFR2 fusion or rearrangement that failed to prior systemic therapy.
ESMO 2021,50P.
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