New targeted drugs treat the recurrence of drug resistance in ovarian cancer
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New Innovative targeted drugs are expected to crack the recurrence of drug resistance in ovarian cancer, with a remission rate of 70%
New targeted drugs treat the recurrence of drug resistance in ovarian cancer. This kind of ovarian cancer has a very high recurrence rate!
Recently, the FDA granted the innovative small molecule RAF/MEK inhibitor VS-6766 breakthrough therapy designation, combined with the FAK inhibitor Defactinib, for the treatment of relapses that have received one or more previous treatments (including platinum-containing chemotherapy) Patients with low-grade serous ovarian cancer (LSOGC), regardless of their KRAS status.
Early clinical trial results showed that the ORR of combination therapy in patients with KRAS mutant tumors was 70%, and the ORR in patients with KRAS wild-type tumors was 44%.
▌This kind of ovarian cancer has a very high recurrence rate!
Low-grade serous ovarian cancer (LGSOC) is a recurrent, chemotherapy-resistant cancer with a high mortality rate. It accounts for approximately 5-10% of serous ovarian cancers and 6-8% of all ovarian cancers.
Approximately 80,000 people worldwide are diagnosed with LGSOC, most often in women aged 45-55. The median survival time of the disease is about 10 years. As the disease progresses, 85% of patients will relapse and need to endure severe pain and complications.
Currently, the standard treatment for this disease is chemotherapy, but the response rate of chemotherapy is low and it is not well tolerated. Therefore, patients need better treatment options.
Most low-grade serous ovarian cancers are driven by the RAS pathway. The RAS gene is one of the most widespread oncogenic mutation genes. The currently known members of this gene family include KRAS, NRAS, and HRAS. They are oncogenes for which there is no targeted drug, and they are also the focus of research. Among them, KRAS mutations are the most common, accounting for about 85%.
Dr. Castro pointed out that KRAS used to be regarded as an oncogene that was “unable to be a drug”. Currently, no targeted drugs have been approved, and it is called “the most difficult target to overcome.” However, in recent years, major breakthroughs have been made in the research of KRAS direct inhibitors and downstream pathway inhibitors, which are expected to improve the prognosis and survival rate of patients with KRAS mutations.
KRAS targeted therapy has made significant progress in the field of lung cancer and pancreatic cancer, and now in the field of ovarian cancer, KRAS downstream pathway targeted drugs have also made new breakthroughs, which are worth looking forward to.
▌Double Functions: RAF / MEK inhibitor VS-6766
As the most common mutated oncogene, RAS occurs in about 30% of human cancers. These cancers are typically highly aggressive and recurrent, and send signal commands through the RAS pathway.
However, cancer cells are often very “cunning” and will look for other ways when “this way is nowhere.” Inhibition of the RAS signaling pathway may cause cells to activate FAK-mediated signaling pathways, which may lead to resistance to RAS-targeted drugs.
VS-6766 is a new type of RAF/MEK dual signaling pathway inhibitor, which can block MEK kinase activity and at the same time block the ability of RAF to phosphorylate MEK. With this unique dual mechanism of action, VS-6766 can vertically inhibit the RAS pathway in a single drug.
Defactinib can specifically inhibit the activity of FAK and related protein kinase PYK2. The combination of the two drugs can more comprehensively inhibit the development of drug resistance in cancer cells.
With dual RAF/MEK inhibitors, it is expected that more patients with KRAS mutations will benefit from targeted therapy.
▌The total remission rate is 70%, and the recurrence of drug resistance in ovarian cancer is expected to be solved!
Early data submitted at the second RAS Targeted Drug Development Summit last year showed:
◆ Among the 17 patients with LGSOC, the ORR of the combined treatment regimen was 41%, all of which were partial remissions. In 9 patients with KRAS G12V mutations, the ORR was 56%.
◆ The FDA’s breakthrough therapy designation is based on an ongoing Phase 1/2 FRAME study, which evaluated the efficacy and safety of VS-6766 and Defactinib in patients with LGSOC, KRAS mutant NSCLC, and colorectal cancer. Sex.
Early results show:
In 21 evaluable low-grade serous ovarian cancer patients, the overall response rate of combination therapy reached 52%.
Among them, the ORR of 10 KRAS mutation patients was 70%, and the ORR of 9 KRAS wild-type patients was 44%.
In addition, some patients have been treated for more than a year, indicating that the therapy has the potential as a long-term treatment option. Moreover, the adverse effects of the combination therapy can be reversed, and the safety and tolerance are good.
Currently, this clinical trial is also verifying its efficacy in patients with pancreatic cancer, KRAS mutant endometrial cancer, non-small cell lung cancer, and metastatic uveal melanoma.
The VS-6766 combination therapy has produced strong and lasting remission in LGSOC patients. It is expected that the drug will be approved as soon as possible and benefit more patients with refractory solid tumors.
New targeted drugs treat the recurrence of drug resistance in ovarian cancer
(source:internet, reference only)
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