In the Chinese tradition, after the lunar year, the new year really begins, the Spring Festival holiday is over, all walks of life are gradually on the right track, and the cancer editors have also begun to choose topics and write. We select from a large body of research literature and strive to share the most up-to-date and useful information with you, even if it is only a small help, our work is worth it.
In all the research literature, what we most urgently want to share with you at the first time is often a certain type of tumor that has not had any previous research progress, and suddenly has new research data, and the drugs in clinical trials have been listed and can be bought on the market. This type of information is undoubtedly a shot in the arm for patients who have been waiting with hope.
Today's article shares the results of one such study, newly published in the top academic journal New England Medicine, which combines the anti-angiogenesis-targeted drug lenvatinib and the PD-1 inhibitor pambolizumab, showing excellent efficacy in the second-line treatment of advanced endometrial cancer.
Advanced endometrial cancer lacks effective treatment
Worldwide, the incidence of endometrial cancer is increasing, with approximately 10% to 15% of patients having advanced endometrial cancer, and a 5-year survival rate of only 17% if distant organ metastases are present. The primary treatment for advanced endometrial cancer is platinum-based chemotherapy, and if platinum-containing chemotherapy fails, there is currently no effective treatment for recurrent advanced endometrial cancer.
Anti-angiogenic targeted drugs were tried to treat advanced endometrial cancer in the second line, with a treatment response rate of only 14.3%. PD-1 inhibitors have been reported to be effective against endometrial cancers with highly unstable microsatellites, with high treatment response rates and longer efficacy. However, only 16%-31% of endometrial cancers are microsatellites of highly unstable types. PD-1 inhibitors do not respond well to patient groups with stable microsatellites or no mismatch repair defects (pMMR).
Based on some previous studies, medical workers conducted a clinical trial to treat recurrent advanced endometrial cancer in the second line by combining the anti-angiogenesis-targeted drug lenvatinib with PD-1 inhibitors. Let's take a look at the efficacy data.
The invincible Coke combo once again delivered a beautiful answer
This is a Phase III clinical trial of 827 patients with advanced endometrial cancer after the failure of platinum-containing chemotherapy. Of these, 697 patients did not have a genetic mismatch repair defect (pMMR) and 130 patients had a genetic mismatch repair defect.
Patients were randomly divided into two groups: the trial group used lenvatinib plus pambolizumab (PD-1 inhibitor), and the control group received chemotherapy with doxorubicin (doxorubicin) or paclitaxel.
1. Drug regimen of the experimental group: 20 mg of lumpatinib per day, injected with pambolizumab every 3 weeks;
2. Control group medication regimen: doxorubicin (60 mg per square body surface area) every three weeks, or paclitaxel (80 mg per square body surface area) every three weeks.
Figure 1. PFS data of cola combination combined with PD-1 versus chemotherapy for endometrial cancer
As shown in the figure above, the results show that the efficacy of renvatinib combined with PD-1 inhibitors is significantly better than that of chemotherapy regardless of whether the patient has a genetic mismatch repair defect. The median progression-free survival for patients without a genetic mismatch repair defect (pMMR) was 6.6 months, compared with 3.8 months for chemotherapy in the control group. The median progression-free survival was 7.2 months for all groups of patients, compared with 3.8 months for chemotherapy in the control group.
Figure 2. OS data of lenvatinib combined with PD-1 versus chemotherapy for the treatment of endometrial cancer
Let's look at the total lifetime data again. For patients without a genetic mismatch repair defect (pMMR), the median overall survival of the cola combination was 17.4 months, and the median overall survival of chemotherapy patients in the control group was 12 months. For all patient groups, the median overall survival of the cola combination was 18.3 months, while the median overall survival of the control group was 11.4 months.
In terms of adverse reactions, the data of the two groups of patients did not differ much. 88.9% of patients in the cola combination had adverse reaction events of level 3 or above, and 72.7% of patients in the chemotherapy group had adverse reaction events.
New hope starts here
In general, microsatellite instability requires genetic sequencing to verify, while gene mismatch repair defects can be detected by immunohistochemistry. If there is a defect in genetic mismatch repair, it is equivalent to a microsatellite high instability.
In the above study data, regardless of whether the patient has a genetic mismatch repair defect, the K drug of lunvatinib combined with PD-1 inhibitors is significantly better than chemotherapy. Therefore, for patients with recurrent advanced endometrial cancer, they can choose not to do gene sequencing, and the use of cola combinations can also obtain better treatment results.
The results of this study are just the beginning, and we know that radiation therapy also increases the efficacy of PD-1 inhibitors to some extent, and radiation therapy is an important treatment for endometrial cancer. Are there any future studies that can combine remvatinib, PD-1 inhibitors, and low-dose radiotherapy? Will this lead to better treatment results? Patients benefit longer, let's look forward to it together.
参考文献：V. Makker, N. Colombo, et al., Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer, n engl j med,2022.