Highlights of this article
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Tumor growth requires nutrients from abundant blood vessels. Ramucirumab, a class of targeted drugs that inhibit angiogenesis, acts on the vascular endothelial growth factor receptor (VEGFR) target to block tumor angiogenesis and thereby cut off its nutrient supply and exert anti-tumor effects.
Based on this mechanism of action, ramolutumab can also work in gastric cancer, extending the median survival of patients with advanced gastric cancer by about 2 months in second-line therapy, meaning that half of patients can survive 2 months or more after treatment. At the current level of diagnosis and treatment, the median survival time for advanced gastric cancer is 8 to 12 months, so a 2-month extension is a big improvement for gastric cancer treatment and a notable improvement for patients.
Remolimumab has been available in the US for 4 years
Remolimumab was launched in the United States in 2014 and is approved by the U.S. Food and Drug Administration (FDA) for patients with advanced or metastatic gastric cancer or adenocarcinoma of the gastroesophageal junction who have disease progression during or after treatment with fluorouracil- or platinum-containing chemotherapy regimens, either with ramolimumab alone or in combination with paclitaxel ( Paclitaxel). The National Comprehensive Cancer Network (NCCN) guidelines also clearly recommend ramolutumab for the second-line treatment of locally advanced, recurrent or metastatic gastric cancer. This shows that in the United States, ramolutumab has clearly become one of the options in the second-line treatment of advanced gastric cancer.
Remolimumab, alone or in combination, is a good choice for second-line treatment of advanced gastric cancer
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Remolimumab has had promising results in a series of studies prior to its launch in the United States.
In the REGARD study in multiple countries, the use of ramolutumab in combination with best supportive care in second-line therapy for advanced gastric or gastroesophageal junction adenocarcinoma increased overall survival by 1.4 months (from 3.8 months to 5.2 months) and increased progression-free survival (PFS) from 1.3 months to 2.1 months compared with best supportive care alone. That is, the time to control tumor progression was extended. Ramulizumab demonstrated a favorable safety profile, with no significant increase in adverse events such as malaise, abdominal pain, decreased appetite, nausea, constipation, anemia, and dysphagia, except for an increased incidence of hypertension (16% and 8%, respectively).
Remolimumab has also shown good efficacy when combined with chemotherapy drugs. The RAINBOW study in multiple countries, also for second-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma, demonstrated that ramolutumab in combination with paclitaxel significantly prolonged survival by 2.2 months (from 7.4 months to 9.6 months) and doubled the time to control tumor progression, with PFS extending from 2.2 months to 4.4 months compared with paclitaxel alone. However, it should be noted that there was an increased incidence of no less than grade 3 adverse events, including neutropenia, leukopenia, hypertension, and fatigue, in patients on ramolutumab.
Based on these two studies, the FDA approved ramolutumab alone or in combination with paclitaxel for second-line treatment of advanced gastric cancer in 2014, and the above-mentioned use of ramolutumab is clearly recommended by the NCCN guidelines.
Remolimumab is not “for everyone”
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While ramolutumab performed well in these studies, it is not for everyone. Remolimumab is not recommended for patients who have had major surgery within 28 days; have a history of deep vein thrombosis, pulmonary embolism, or other severe thromboembolism; are receiving anticoagulation with favalin, low-molecular-weight heparin, or similar agents; are receiving ongoing treatment with nonsteroidal anti-inflammatory drugs or other antiplatelet agents; have severe bleeding disorders, vasculitis, or severe gastrointestinal bleeding; have a history of gastrointestinal perforation and/or fistulae; have symptomatic congestion; or have a history of fistulae. history of symptomatic congestive heart failure, or symptomatic or poorly controlled arrhythmias; uncontrolled arterial hypertension even with standard therapy; severe or unhealed wounds, ulcers, or fractures; and intestinal obstruction.
How far is ramolutumab from our patients?
Regrettably, ramolutumab is not yet available in China. To confirm the role of ramolutumab in the Chinese population, researchers in China are actively conducting studies. Patients with advanced gastric cancer or combined gastroesophageal adenocarcinoma who are resistant to or have disease progression after first-line treatment with platinum-based drugs in combination with fluorouracil-based drugs are currently enrolled in a study numbered CTR20160574 registered on the China Drug Clinical Trials Registration and Information Publicity Platform (http://www.chinadrugtrials.org.cn/eap/main). Patients with advanced gastric or gastroesophageal adenocarcinoma that is resistant to or has progressed after first-line treatment with platinum- and fluorouracil-based agents may be considered for the study, in which patients will likely receive a regimen of ramolutumab in combination with paclitaxel. It is believed that this study will bring evidence for the use of ramolutumab in patients with gastric cancer in China, and may even promote its marketing. The clinical study also provides free access to the drug for our patients, and 24 medical institutions in China are currently participating in the study.
Summary
Remolimumab, a targeted anti-angiogenic agent, is available in the United States as a single agent or in combination with paclitaxel for second-line treatment of advanced gastric cancer, and its use has been recommended by US guidelines. With the development of studies in China, ramolutumab is expected to obtain data for application in Chinese gastric cancer patients, providing more treatment options for Chinese gastric cancer patients.