Ramucirumab: Targeted drug for the treatment of various cancers

Ramucirumab: Targeted drug for the treatment of various cancers. Ramucuzumab(Cyramza) is mostly used to treat metastatic EGFR-mutant NSCLC by using small molecule targeted drugs.

Ramulumab (Ramucirumab, Cyramza, US marketed trade name) is a human IgG1 monoclonal antibody that can specifically bind to vascular endothelial growth factor receptor 2 (VEGFR-2) and block VEGFR ligands, VEGF-A, The combination of VEGF-C and VEGF-D inhibits the ligand-stimulated VEGFR-2 activation and the ligand-induced endothelial cell proliferation and migration, thereby inhibiting tumor angiogenesis.

Up to now, ramucirumab has been approved for 6 indications for 4 cancers (lung cancer, liver cancer, stomach cancer and colorectal cancer) in the United States.

In June 2017, Eli Lilly launched the study “Comparing the overall survival time of Ramucirumab and placebo in patients with advanced hepatocellular carcinoma”. The indication is the treatment of hepatocellular carcinoma. The phase III clinical trial is currently under recruitment. Up to now, Chia Tai Tianqing and Sichuan Kelun have respectively completed phase I clinical studies of ramucirumab in the treatment of gastric cancer, non-small cell lung cancer and colorectal cancer.

Today, NMPA released information on December 2 drug approval documents pending receipt, among which Eli Lilly’s ramucirumab received a one-time import approval.

Liver cancer:

Recently, in the 2020 ASCO Advanced Hepatocellular Carcinoma Treatment Guidelines, a variety of treatment options for patients with advanced HCC have been included.

Among them, in the ramucirumumab versus placebo trial (REACH-2), the OS (overall survival) and PFS of patients with AFP (alpha-fetoprotein) ≥400 ng/mL were significantly improved.

The results of the study showed that for liver cancer patients with AFP ≥ 400 ng/mL, the ORR (objective response rate) of hepatocellular carcinoma patients treated with sorafenib was 4.6%, and the median PFS (progression-free survival) Period) was 2.8 months, and the median OS was 8.5 months. Compared with placebo, ramucirumab has a significant improvement in OS and PFS, but there is no significant difference in ORR between the groups.

The ASCO guidelines propose that first-line treatment: atilizumab + bevacizumab is the first choice, if there are contraindications, you can choose sorafenib or lenvatinib. Second-line treatment: For patients treated with atilizumab+bevacizumab, you can choose sorafenib, lenvatinib, cabozantinib, and regafini for second-line treatment; for the use of sorafenib or ren For patients treated with vatinib as the first-line treatment, you can choose cabotinib, regfinib, ramucirumab, pembrolizumab or nivolumab. Third-line treatment: Cabozantinib can be used.

In the second-line treatment recommendation, for patients who have used sorafenib or lenvatinib for first-line treatment, whether or not there is sorafenib resistance, remoru is recommended when AFP ≥ 400 ng/mL Monoclonal antibody. Therefore, the future launch of ramucirumab is expected to provide a new treatment method in the targeted therapy of liver cancer, but the alternative to other second-line therapies for liver cancer is not obvious.

Gastric cancer:

In a global phase III trial called RAONBOW, ramucirumab combined with paclitaxel and placebo combined with paclitaxel were used to treat advanced gastric cancer or gastro-esophageal junction glands that were refractory to second-line treatment or whose condition was still progressing after initial treatment Comparing cancer patients, the median OS was 9.6 months and 7.4 months, the median PFS was 4.4 months and 2.9 months, and the ORR was 28% and 16%, respectively. Ramucirumab showed significant Advantage.

In addition, in the ramolizumab combined with paclitaxel combination treatment group, there were no less than grade 3 adverse events to some extent, including neutropenia (40.7%vs18.8%), leukopenia (17.4%vs6) .7%), hypertension (14.1%vs2.4%), anemia (9.2%vs10.3%), fatigue (7.0%vs4.0%), abdominal pain (5.5%vs3.3%), and fatigue ( 5.5%vs3.3%).

The ramolizumab/paclitaxel combination treatment group had a higher incidence of neutropenia, while the incidence of febrile neutropenia was not much different between the two groups by 3.1% vs 2.4%. Febrile neutropenia is not a big problem, and the combination treatment is safe and easy to manage.

Non-small cell lung cancer:

In December 2014, the FDA approved ramucirumumab combined with docetaxel for metastatic non-small cell lung cancer (NSCLC) with disease progression during or after platinum-containing chemotherapy.

On May 29, 2020, the FDA approved ramucirumumab combined with erlotinib as the first-line treatment of epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R mutation for metastatic non-small Cell lung cancer patients.

Erlotinib is a tyrosine kinase inhibitor (TKI) that can target to inhibit the activity of EGFR kinase. Research data showed that compared with placebo group, the median PFS of the ramucirumab group was 19.4 months and 12.4 months, respectively, which reduced the risk of disease progression and death by 41% (HR=0.59; 95% CI, 0.46 , 0.76; p<0.0001); ORR was 76% and 75%, respectively; median DOR (duration of response) was 18.0 months and 11.1 months, respectively. Among them, the PFS improvement effect of patients with exon 19 and exon 21 mutation subgroups was consistent. As of the time of PFS analysis, OS data is not yet mature.

The combination of ramucirumab and erlotinib is the first VEGFR/EGFR TKI combination therapy approved by the FDA for the treatment of metastatic EGFR-mutant NSCLC. In the European Union, ramucirumab + erlotinib combination therapy was approved in January this year.

From the current situation, the treatment of metastatic EGFR-mutant NSCLC mostly uses small molecule targeted drugs. In the future, with further clinical research on biologics and combination drugs, it may be expected to provide new treatment options for NSCLC patients with metastatic EGFR mutations.

(source:chinanet, reference only)

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