The first-line all-population indication of Odivo® for advanced gastric cancer is grandly launched, fully benefiting and opening up a new "stomach"

Gastric cancer is one of the top three most common cancers in China in terms of incidence and death.
The first-line treatment of advanced gastric cancer is one of the “difficulties” that have always been insurmountable.
For more than ten years, doctors have continued to explore the first-line better than chemotherapy.
Therapy, but it has not been possible; until August this year, with the results of the landmark study CheckMate-649, China’s first immunotherapy Odivo (Navuliumab) was approved for the first-line treatment of advanced gastric cancer in combination with chemotherapy, and Regardless of the expression of PD-L1, the bottleneck of first-line treatment that has been silent for many years finally ushered in a breakthrough, bringing the dawn of life to many Chinese patients
.

On November 27th, "Vitality is in Wo, Stomach Headline" Odivo's first-line indications for advanced gastric cancer was grandly held.
Many domestic and foreign gastrointestinal tumors and surgical experts gathered together through online connection to focus on gastric cancer.
Conduct special reports and discussions on academic topics such as immunotherapy and overall management, share insights, and jointly witness the opening of a new era of gastric cancer treatment in China
.

At the beginning of the conference, Professor Xu Ruihua, Professor Li Jin, Professor Shen Lin, Professor Zhu Zhenggang, Professor Liang Han, Professor Peng Junsheng, Professor Shi Yuankai and many other experts made opening speeches respectively, expressing their opinions on the first-line “whole population” of Odivo’s advanced gastric cancer.
"Blessings of this historic breakthrough in the listing of indications
.

The first-line "stomach" of nivolumab is the first-line "stomach".
The Chinese data proves that the entire population and the full benefits are at the opportunity of this listing.
Professor Liu Tianshu first shared the past treatment pattern and exploration history of advanced gastric cancer in China; Professor Zhang Xiaotian also learned from From the perspective of domestic clinical practice, an in-depth inventory of the CheckMate-649 study and the data of the Chinese population was carried out
.

Chinese gastric cancer patients are generally late at the first diagnosis, with a large tumor burden, a high proportion of metastases, and weak physical fitness [1].
They often do not have the opportunity for back-line treatment.
Therefore, the choice of first-line treatment is very important
.

The ORR of the previous standard first-line chemotherapy is less than 50%, and the DoR is only half a year[2][3][4][5].
Patients who do not respond well to first-line treatment often progress rapidly, leading to a median OS of less than one year
.

In summary, there is an urgent clinical need for new first-line treatment options that can comprehensively improve survival benefits
.

However, the exploration of new first-line treatment options in the past ten years has ended in failure
.

Until 2020, CheckMate-649, the largest prospective study in the field of advanced gastric cancer so far, has finally brought the dawn of the "little dark flower"
.

Click to view CheckMate-649 global population detailed data.
Through in-depth analysis of the CheckMate-649 study and the Chinese subgroup results announced this year, the greatest significance of nivolumab combined with chemotherapy for Chinese patients is that its efficacy is not limited to a single population or index.
Instead, multiple clinical goals such as improving remission rate, lasting symptom relief, delaying disease progression, long-term survival, and safety control have been achieved in the entire population at the same time[6][7], bringing a true sense of "the whole population, All-round" benefits: First, although the overall population OS is the secondary study endpoint of CheckMate-649, the statistical power of the primary endpoint (CPS ≥ 5 population OS) can be transmitted downwards in order to make this endpoint the same.
It has statistical power, and finally passed the hypothesis test with p = 0.
0002 [6]
.

This is also the fundamental basis for the nivolumab + chemotherapy regimen to be approved for all-population indications in the United States and China
.

In terms of disease control, the ORR of nivolumab + chemotherapy for the entire population of Chinese patients can reach 59%, which is nearly 1.
5 times that of the chemotherapy group (41%), and even 68% of patients with CPS ≥5 (48% of the chemotherapy group) Once the patient benefits, the median DoR of the whole population is more than one year (12.
2 months), which is more than twice that of chemotherapy (5.
6 months) [7], indicating that nivolumab + chemotherapy can break through the existing treatment of diseases Control limitations and bring long-term relief
.

In terms of delaying disease progression, nivolumab plus chemotherapy has a median PFS of 8.
3 months in the entire population of Chinese patients, which is nearly 1.
5 times that of chemotherapy (5.
6 months), and the risk of disease progression or death is reduced by 43%; PFS in patients with CPS ≥ 5 It can reach nearly 2 times of chemotherapy (8.
5 months, 4.
3 months in the chemotherapy group), reducing the risk of disease progression or death by 48% [7]
.

In terms of overall survival, the median OS of Chinese patients receiving nivolumab + chemotherapy was 14.
3 months, an increase of 4 months (10.
3 months) compared with the chemotherapy group, and the risk of death was reduced by 39%; CPS ≥ 5 patients with OS It reached 15.
5 months, nearly half a year (9.
6 months) beyond the chemotherapy group, and the risk of death was reduced by 46% [7], which completely broke the bottleneck of the existing treatment of OS for less than one year
.

In addition, the program is safe and reliable, the incidence of 3-4 potential immune-related TRAEs is ≤5%, and no immunotherapy-related deaths occurred [7]
.

Click to view the detailed data of the CheckMate-649 Chinese subgroup.
At the same time, the program is based on a large research sample size, including a large number of Chinese patients (the proportion of Chinese patients is the largest in all countries), and the baseline characteristics of each group are well-balanced and close to clinical practice in China For example, the proportion of patients with metastasis is 99%, more than 50% of patients have liver metastasis, and the patients with PS = 1 account for more than 70% [7], which shows that the research design is rigorous and the results are highly reliable
.

In summary, the CheckMate-649 study has achieved a "leap" in the efficacy of advanced gastric cancer in China in the past ten years.
Nivolumab + chemotherapy has therefore become China's first and currently the only approved first-line immunization for advanced gastric cancer in the whole population.
Therapy, and received the highest level recommendation consistent with domestic and foreign guidelines such as CSCO[8] and NCCN[9]
.

Based on the indications approved for marketing this time, in the future update of the guidelines, the recommended population of this program is expected to be expanded to the entire first-line population at the same time, thereby benefiting a wider range of patients
.

A global perspective and long-term data testify that immunotherapy opens the "stomach" Professor Kei Muro from Japan provides an international perspective for the exploration of advanced gastric cancer treatment
.

Professor Muro introduced the exploratory experience of advanced gastric cancer in Japan over the past 15 years, and pointed out that the application of immunotherapy is an important turning point; especially the success of CheckMate-649 research has brought the long-awaited new standard for advanced gastric cancer.
Treatment
.

Just this week, based on the results of CheckMate-649, the nivolumab + chemotherapy regimen was also approved in Japan for the first-line treatment of advanced gastric cancer, regardless of PD-L1 expression level [10]
.

Professor Muro also shared the recently announced CheckMate-649 study of the global population’s 2-year follow-up results.
The data showed that nivolumab + chemotherapy can bring continuous and deep benefits to first-line patients with advanced gastric cancer [11], especially PFS, The continued benefits of ORR, DoR, and TTSD are of great significance for relieving symptoms and improving quality of life, and are in line with the current treatment goals and concepts of advanced gastric cancer; at the same time, the benefits are not limited by PD-L1, suitable for almost all first-line patients, and will profoundly change the advanced stage First-line treatment strategies for gastric cancer
.

Immunotherapy is advancing in multiple lines, and "good medicine first" helps benefit the whole process.
The theme of the second half of the conference focuses on the full management of immunotherapy for advanced gastric cancer, which is divided into two major conference venues in Shanghai and Beijing
.

Professor Fenghua Wang and Professor Bai Li respectively shared the exploration and application of the whole-process management model for advanced gastric cancer in the immunotherapy era; then, Professor He Yifu and Professor Zhao Ping each reported a clinical case of standardized immunotherapy for advanced gastric cancer
.

Experts unanimously agree that a full-process management model is imperative in the treatment of gastric cancer.
After nivolumab is approved for third-line and first-line indications in China, it will play an important role with its curative advantages and multi-line coverage.
The timing of choosing immunotherapy has become an important factor in overall management
.

Following the concept of "good medicine early use", the first-line regimen of nivolumab + chemotherapy may maximize the patient's overall benefit, while its adverse reaction rate is controllable, and it also lays a good foundation for the patient's overall irAE management
.

As an important part of the overall management concept, multidisciplinary diagnosis and treatment (MDT) has become the mainstream treatment model for advanced gastric cancer
.

In the afternoon of the same day, the China Cancer MDT Alliance 2021 annual work summary meeting and the "Wo Zhuweilai" digestion tumor immunity MDT project kick-off meeting was also officially held online.
Many domestic cancer experts gathered in the cloud to review the standardized construction of domestic tumor MDT.
Work, and look forward to the new opportunities for the development of gastrointestinal cancer MDT brought about by the innovative progress represented by immunotherapy
.

References [1] Wang H, et al.
Mol Clin Oncol.
2018;9(4):423-431.
[2] Luo HY, et al.
Chemotherapy 2010;56(2).
94-100.
[3] Liu c, et al.
Anticancer Drugs 2008;19(8):825-31.
[4] Xiao C, et al.
Medicine (Baltimore) 2019;98(20): e15696.
[5] Chen J, et al.
Asia Pac J clin Oncol 2018;14(5): e310-e316.
[6] Janjigian YY, et al.
Lancet.
2021 Jul 3;398(10294)27-40.
[7] Shen L, et al.
2021 AACR #CT184.
[8] Chinese Society of Clinical Oncology (CSCO) Gastric Cancer Diagnosis and Treatment Guidelines 2021 Edition.
[9] 2021.
V3 NCCN Clinical Practice Guidelines: Gastric Cancer.
[10] ONO Receives Approval of Opdivo® (nivolumab) for Expanded Use for Two Indications in Japan | ONO CORPORATE (ono-pharma.
com)[11] Janjigian YY, et al.
ESMO 2021 LBA 7.