End a decade of "drug shortage"! Targeting treatment for stomach cancer or ushering in new breakthroughs

On January 17, 2021, the world's premier academic event in the field of gastrointestinal tumors was officially concluded at the 2021 American Society of Clinical Oncology Gastrointestinal Oncology (ASCO-GI) Virtual Conference. Results were updated in more than
heavyweight studies, with the new drug Bemarituzumab becoming one of the hot topics discussed at this conference, and bemarituzumab's combined chemotherapy first-line treatment FGFR2b over-expression gastric cancer achieved a double improvement in progress-free survival (PFS) and total survival (OS) in the simple chemotherapy group, bringing hope for targeted treatment of stomach cancer in the dark.
'll take a look at it.
research on targeted treatment for stomach cancer has been difficult, and in the past decade, only two clinical results related to HER2 targeted drugs have been positive, curtoju monoantin and DS-8201.
addition to this, studies of other targets have been conducted in the sand.
the drug shortage continued for a long time until the release of the results of the FIGHT II. clinical study at the ASCO GI Conference recently.
as a new antibody drug targeting FGFR2b, bemarituzab promises to end a decade-long drug shortage of stomach cancer, giving hope to countless patients struggling.
bemarituzumab, a "first-in-class" FGFR2b monoclonal antibody drug developed by Five Prime Therapeutic.
it has a dual mechanism of action, not only by binding with FGFR2b, blocking the signaling of its mediated growth factors, but also by antibody-dependent cell-mediated cytotoxic action (ADCC) to kill cancer cells.
the workings of Bemarituzumab Photo Source: FIGHT Research Design FIGHT, a randomized, double-blind, placebo-controlled study.
group criteria: previously untreated non-removable local advanced or metastatic gastric/gastroesophageal binding adenocarcinoma, with refractionable lesions as measured according to RECIST standard, IHC determination FGFR2b protein overexpression and/or CTDNA determination FGFR2 gene amplification, ECOG score 0 or 1 point, HER2 non-positive.
baseline characteristics of patients in the 1st group were obtained from Document 1 entry group patients who were randomly accepted by Bemarituzumab (Bema) plus mFOLFOX6, or placebo with mFOLFOX6.
bemarituzumab is used once on the 8th day of the first cycle at a dose of 7.5 mg/kg.
end point is the progress-free lifetime (PFS) assessed by the researchers, and the secondary endpoint is total lifetime (OS) and mitigation rate.
study design Images from Literature 1 from September 28, 2018 to May 12, 2020, a total of 910 patients were screened, of which 275 were FGFR2b-positive, and 155 patients met the criteria and received random groupings, including 77 cases in bema-mFOLFOX6 and 78 in the placebo-mFOLFOX 6 group.
the baseline features between the two groups are roughly balanced.
until the data closed on September 23, 2020, 42 cases in the Bema group were still being treated in the study and 27 in the placebo group.
follow-up time was 10.9 months.
results show that all three efficacy endpoints in the experiment achieved pre-specified results, and the results were statistically significant.
bema group vs. placebo group: medium progression-free lifetime (mPFS), 9.5 months vs 7.4 months, 32 percent lower risk of disease progression;
PFS (left) and OS (right) results for the total population Images from Reference 1 It is worth noting that the researchers further analyzed the results and found that FGFR2b over-expression of positive tumor cells accounted for a higher proportion of the population, the overall survival rate is higher.
12-month survival rate was as high as 70.2 percent in patients with IHC 2 plus/3 plus ≥10 percent, compared with 49.5 percent in the placebo group.
addition, the risk of death was reduced by 59% ≥ 10% of patients with IHC 2 plus/3 plus 3 plus.
OS benefits increased with an increase in FGFR2b over-expression Image from Reference 1 Safety, the overall occurrence of adverse events (AEs) at all levels in the Bema and placebo groups was similar, with a slightly higher ≥3-level AE occurrence bema group (82.9% vs 74.0%), but a lower serious AE occurrence rate in the Bema group (31.6 vs 36.4%).
bema group had a higher rate than the placebo group≥ level 3 AE was mainly stomatitis (9.2% vs. 1.3%) and eye dry (2.6% vs. 0).
toxicity is controllable in general.
30% of non-HER2-positive gastroesophageal cancer patients over-expression FGFR2b.
addition, FGFR2b over-expression has been found in squamous non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), ovarian cancer, pancreatic cancer, and intra-liver bile tube cancer.
suggests that Bemarituzumab may have therapeutic potential in more tumor types.
bemarituzumab is the first and only experimental treatment to target FGFR2b-positive tumors.
the initial success of its FGFR2b target gives us new hope.