Open up the new "Xi" hope for the second-line treatment of advanced gastric cancer, and talk about the prospect of the use of ramoximumab

*For medical professionals only

What is the status of ramoximab in the treatment of advanced gastric cancer? Three domestic celebrities to answer

In October 2022, based on the results of the global phase III.
REACH-2 study, the anti-angiogenic drug remoximab (trade name: Hoperanji) was approved by the National Medical Products Administration (NMPA) for the treatment of patients with hepatocellular carcinoma (HCC) who had previously received sorafenib treatment and had alpha-fetoprotein (AFP) ≥ 400 ng/mL, providing a new treatment option for liver cancer patients in China, and it is also the second indication for digestive tumors approved in China in 2022
。

The first indication of remoximab approved was based on the results of RAINBOW-Asia research, combined with chemotherapy for the second-line treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma, and ramoximab combined with paclitaxel has also become the first and only anti-angiogenic drug
approved for the second-line treatment of advanced gastric cancer in China 。 On the occasion of the approval of ramoximab for liver cancer indication, the "Medical Tumor Channel" specially invited Professor Shen Lin of Peking University Cancer Hospital, Professor Qin Yanru of the First Affiliated Hospital of Zhengzhou University and Professor Niu Zuoxing of Shandong Cancer Hospital to discuss the current status and development prospects
of ramoximab in the treatment of advanced gastric cancer with three big coffee.

After a bumpy exploration, the status quo of second-line treatment of advanced gastric cancer is still not ideal

According to the 2020 Global Cancer Statistics Report (GLOBOCAN) released by the World Health Organization's International Agency for Research on Cancer (IARC), the number of new gastric cancer cases in China reached 478,500 in 2020, accounting for 43.
9% of the world; Deaths also reached 373,800, accounting for 48.
6% of the global ^total[1].

Moreover, due to the limited coverage of health examination and cancer screening, the early diagnosis and early treatment of gastric cancer in China has not been fully carried out, resulting in a high proportion of gastric cancer patients diagnosed in the advanced stage, these patients have no chance of surgical radical treatment, and the clinical benefits of previous systemic drug treatment are relatively limited, so the overall prognosis of patients is very poor, and the 5-year survival rate is still less than 20% ^[2].

As a senior expert in the diagnosis and treatment of digestive tract tumors, Professor Shen Lin has a deep understanding of the difficulty of systematic treatment of advanced gastric cancer, especially second-line treatment, "Many clinical studies have been carried out in the past, but unfortunately they have failed one by one, so before the launch of ramoximumab, we only have yechtaxis and irinotecan options in the second-line treatment, but irinotecan treatment has a relatively low efficiency and toxicity, if the patient has also used yew drugs in the first line, then the second-line or even third-line treatment is basically unavailable.
Therefore, the survival period of patients is still relatively limited, and there is a very large demand
for new treatments.
”

Therefore, in view of the problems faced in clinical practice, the successful approval of ramoximab will allow clinicians and patients to obtain new treatment options, and the success of the RAINBOW-Asia study provides key evidence-based medical evidence
for the use of ramoximab in the second-line treatment of advanced gastric cancer patients in China.

Research shows clear benefits, ramoximab helps gastric cancer treatment in China

As the principal investigator of the RAINBOW-Asia study, Professor Shen Lin answered the significance of the study to Chinese patients, "For various reasons, Chinese researchers unfortunately could not join the RAINBOW global clinical trial, and the RAINBOW-Asia study is a bridging study, but its sample size is much larger than the general bridging study, so it can provide Chinese patients with " Based on the evidence of Chinese population needs and clinical characteristics', and this study also provides a lot of other information, such as the impact of follow-up immunotherapy, patient survival in the new era, etc.
, which is of reference value
for gastric cancer treatment worldwide.
”

Professor Qin Yanru, who participated in the RAINBOW-Asia study, introduced the design and main results
of the study in detail.
The RAINBOW-Asia study is a phase III clinical study that included a total of 440 patients from East Asia (China, Malaysia, the Philippines and Thailand) who progressed after first-line chemotherapy with advanced gastric cancer or gastroesophageal junction adenocarcinoma, of which patients in China accounted for the vast majority, and were randomized to remoximab + paclitaxel or placebo + paclitaxel in a 2:1 ratio
.

The results showed that median progression-free survival (PFS) was significantly longer in the ramoximab plus paclitaxel group than in the placebo group (4.
14 months vs.
3.
15 months, HR=0.
765, P=0.
0184)^[3], and showed a median overall survival (OS) benefit consistent with the global pivotal registry clinical trial RAINBOW (9.
03 versus 8.
08 months, HR=0.
942).

Patients were generally well tolerated and consistent with the known safety profile of ramoximumab, no new safety signals
were observed.

"The RAINBOW-Asia study is the first and only phase III study to confirm the clinical benefit of antiangiogenic therapy in the second-tier population of advanced gastric cancer, mainly in Chinese patients, thus providing a new standard treatment for
such patients in China.
" Professor Qin Yanru said, "In the past, because ramoximab was not available in China, treatment could only use paclitaxel or irinotecan, but now ramoximab has been officially approved for marketing, allowing more patients to use the drug to significantly prolong survival
.
" ”

Real-world performance is also impressive, and the future of ramoximab is promising

At present, there have been a number of real-world studies abroad, evaluating the value of ramoximab combined with paclitaxel chemotherapy for the second-line treatment of advanced gastric cancer, Professor Niu Zuoxing introduced a national real-world study in South Korea, which enrolled a total of 1063 patients whose disease progressed after first-line platinum and fluorouracil combined with chemotherapy, and the median OS of remoximab + paclitaxel in such patients reached 10 months ^[4].
, the efficacy is considerable; In another post-marketing observational study conducted in Japan, a median OS of 528 patients receiving remoximab + paclitaxel second-line therapy reached 11 months ^[5].

In addition, Professor Niu Zuoxing also pointed out that in recent years, the standard regimen of first-line treatment of advanced gastric cancer has gradually changed to combination therapy + chemotherapy, and real-world data from the United States have shown that the efficacy of remoximab in the second line of such patients may be better [^6], which is worthy of further verification by follow-up studies
.

After the approval of the NMPA indication on March 18, the second-line treatment regimen of ramoximab combined with paclitaxel quickly obtained the 2022 version of the "Chinese Society of Clinical Oncology (CSCO) Gastric Cancer Diagnosis and Treatment Guidelines" level I recommendation (class I.
A evidence), so that the application of the program has been rapidly popularized, Professor Qin Yanru said that the current clinicians recommend the ramoximab + paclitaxel regimen "more confident and confident"
.

Professor Shen Lin combined with the medication experience and emphasized the advantages of ramoximab + paclitaxel in many aspects, "First of all, from the perspective of safety, ramoximab combined with paclitaxel, except for hypertension, the adverse events are relatively mild, and the safety is significantly better than that of small molecule TKI
when used in advanced gastric cancer people with poor overall tolerance.
" The success of remoximumab in terms of efficacy can be said to have brought historic changes to the second-line treatment of advanced gastric cancer, and the significance is incomparable
.
”

In addition, Professor Shen Lin also introduced that ramoximab is being further explored for the treatment of HER2-positive (such as HER-RAM study ^[7]) and HER2-negative gastric cancer, and preliminary studies have shown that it has a synergistic trend with targeted therapy and immunotherapy, laying a solid foundation
for future exploration.
In terms of clinical recommendations, Professor Shen Lin believes that in addition to strictly monitoring the blood pressure of some high-risk patients, the ramoximab + paclitaxel regimen is very friendly to both doctors and patients, and is an efficient and reliable treatment plan
.