​The first domestic CDK4/6 inhibitor Dulceli was approved for marketing; probiotics are not good for melanoma immunotherapy?

*Only for medical professionals to read for reference, 1 minute a day, to give you professional "talking information" in the tumor circle! (If you need the original text of the document, you can add the editor WeChat yxj_oncology to get it) Key points JAMA Oncol: The effect of gonadotropin releasing hormone analogues on ovarian function in patients with premenopausal breast cancer.
Science: Dietary fiber and probiotics on the gut microbiome and melanin New drug: The first domestic CDK4/6 inhibitor Dalceli was approved for marketing.
Frontier: The latest version of the National Medical Insurance Catalogue took effect, Zebutinib was once again reduced in price, and the lowest mid-month treatment cost for similar BTK 01JAMA Oncol: Gonadotropin The effect of releasing hormone analogues on ovarian function in premenopausal breast cancer patients The results of studies on the use of gonadotropin releasing hormone analogues (GnRHa) to protect ovarian function have been mixed
.

A few days ago, JAMA Oncology published a study online to explore whether the application of GnRHa during chemotherapy in premenopausal breast cancer patients can reduce ovarian dysfunction
.

Screenshot of research publication This open-label clinical study enrolled premenopausal women aged 18-49 with operable stage I-III breast cancer.
They plan to use cyclophosphamide as adjuvant or neoadjuvant chemotherapy, and divide the patients into two groups: chemotherapy With or without GnRHa
.

Data analysis was conducted in March 2021.
A total of 405 patients were included, of which 27 patients (6.
7%) voluntarily withdrew, 33 patients (8.
1%) did not meet the inclusion criteria and were excluded, and 15 patients (3.
7%) lost follow-up
.

In the end, 330 patients entered the preliminary analysis
.

Eligible patients were randomly assigned 1:1 to receive chemotherapy plus GnRHa (n=165) and no GnRHa (n=165)
.

The primary endpoint is the incidence of ovarian insufficiency (POI) 12 months after chemotherapy (anti-Müllerian hormone level <0.
5 ng/mL)
.

The secondary endpoints are overall survival (OS) and tumor-free survival (TFS)
.

The results of the study showed that 301 patients (91.
2%) met the criteria for the primary endpoint analysis
.

12 months after chemotherapy, the incidence of POI was 10.
3% (15/146) in the GnRHa group and 44.
5% (69/155) in the control group (OR=0.
23; 95%CI: 0.
14-0.
39; P<0.
001)
.

The recovery of anti-Müllerian hormone in the GnRHa group was significantly better than that in the control group (15/25 vs 6/44; OR = 4.
40; 95% CI: 1.
96-9.
89; P <0.
001)
.

After a median follow-up of 49 months, there was no significant difference in 4-year OS and TFS between the two groups
.

Post-hoc analysis showed that in patients under 35 years of age, the TFS of the GnRHa group was higher than that of the control group (93% vs 62%; P=0.
004; HR=0.
15; 95%CI: 0.
03-0.
82; P=0.
03)
.

The study showed that the use of GnRHa in the chemotherapy of premenopausal breast cancer patients can reduce the risk of POI, thereby promoting the recovery of ovarian function
.

02Science: The influence of dietary fiber and probiotics on the intestinal microbiome and the efficacy of melanoma immunotherapy.
Previous studies have suggested that intestinal microbes may play an important role in tumor immunotherapy
.

Some retrospective studies have reported that the application of antibiotics affects the prognosis of immunotherapy, and it has been observed in some preclinical studies that probiotic supplements may promote the effect of immunotherapy
.

However, recently published a study on the effect of dietary fiber in the diet on the efficacy of immunotherapy for malignant melanoma in the journal Science.
Among them, the application of probiotic supplements (Bifidobacterium longum, Lactobacillus rhamnosus) is not Conducive to immunotherapy
.

Screenshot of research publication.
The study included and analyzed the intestinal microbes and clinicopathological characteristics of 438 patients with malignant melanoma, of which 321 received systemic treatment, and 293 were evaluable.
According to the RESCIST1.
1 standard, patients were classified as remission patients ( n=193) and those without remission (n=100), 87% of the patients received anti-PD-1 immunotherapy.
The patients joined the life>
.

Similar to previous studies, Verrucomicrobiaceae and Faebacterium spp.
are more abundant in patients who have responded to immunotherapy
.

However, no significant difference in the diversity of α and β was observed in immunotherapy patients with and without remission
.

Among the 158 patients, 31% (49) of patients with advanced melanoma had taken probiotic supplements one month before the start of treatment.
Compared with patients who did not take probiotic supplements, this part of the patients had a lower body mass index (BMI) , The possibility of taking statins is low, the intake of vegetables and beans is slightly higher, and the proportion of antibiotic use is similar (29% vs 28%)
.

The researchers did not observe that the two groups of patients were statistically significant in terms of immunotherapy results and intestinal microbial characteristics, but the overall trend seems to be unfavorable for taking probiotics [taking probiotics vs.
not taking: progression-free survival (PFS) 17 months vs 23 months, objective response rate (ORR) 59% vs 68%], so the investigator continues to conduct the next step in the preclinical model
.

Compared with patients with insufficient dietary fiber intake (n=91), patients with sufficient dietary fiber intake (n=37) have improved PFS with immunotherapy (PFS less than 13 months; HR=0.
59); after adjusting for clinical factors, Every increase of 5g of daily dietary fiber intake reduces the risk of deterioration or death by 30%; the relationship between dietary fiber intake and the ORR of immunotherapy also has similar results; through 16S and metagenomic sequencing, no patients with sufficient or insufficient dietary fiber intake have been observed Substantial differences in the gut microbiota
.

To evaluate the effect of dietary fiber intake and taking probiotics on immunotherapy
.

Those who have sufficient dietary fiber intake and do not take probiotics have the best immunotherapy effect.
In these patients, the alpha diversity of the gut microbes and the abundance of Verrucomicrobia and Faebacterium are also higher, although they are not statistically significant.
Difference
.

The study shows that more research is needed to explore whether dietary interventions can promote the efficacy of immunotherapy
.

Is taking probiotics beneficial or harmful to immunotherapy? There have been different results in previous studies and this study, and more studies may be needed in the future to clarify, and clinical application needs to be cautious
.

03New Drug: The first domestically produced CDK4/6 inhibitor Dulceride was approved for marketing on December 31, 2021, Hengrui Medicine's CDK4/6 inhibitor Dulceride tablets was officially approved by the National Medical Products Administration (NMPA) On the market, combined with Fulvestrant, it is suitable for hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) recurrent or metastatic breast cancer patients who have experienced disease progression after receiving endocrine therapy.
This is Hengrui's 10th innovative drug approved
.

Screenshot of NMPA official website CDK4/6 is a key factor that regulates the cell cycle, which can trigger the transition of the cell cycle from the growth phase (G1 phase) to the DNA replication phase (S phase)
.

Dulceli is a new class 1 drug developed by Hengrui.
It is an oral, highly effective and selective small molecule CDK4/6 inhibitor that can block the cell cycle at the G1 phase, thereby inhibiting tumor cell proliferation
.

On December 24 last year, Hengrui announced a multicenter, randomized, controlled, double-blind phase III clinical study of Dalceli combined with fulvestrant in the treatment of HR+ and HER2- for locally advanced or advanced breast cancer after endocrine therapy.
(SHR6390-III-301) Reach the superiority standard preset by the program
.

The results of the study show that for patients with HR+ and HER2- advanced breast cancer who have previously used endocrine therapy, receiving Dalceride combined with fulvestrant compared with placebo combined with fulvestrant can significantly prolong the PFS of the patients
.

04 Frontier: The latest version of the National Medical Insurance Catalogue takes effect, and the price of Zebutinib is reduced again.
On January 1, 2022, the new version of the National Medical Insurance Catalogue is officially implemented
.

BeiGene's BTK inhibitor Zebutinib, after the 2021 medical insurance catalogue negotiations, successfully added the indication for Waldenstrom's macroglobulinemia (WM) into the 2021 edition of the national medical insurance catalogue, further reducing the financial burden of patients
.

Currently, Zebutinib has three indications included in the medical insurance catalog, covering mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and Waldenstrom's macroglobulinemia
.

This time, Zebutinib reduced the price by 14% after the 44% price cut in the medical insurance negotiations in 2020
.

 Zebutinib is a new generation of BTK inhibitor independently developed by BeiGene.
After being approved for marketing by the U.
S.
Food and Drug Administration (FDA) in November 2019, it has been sold in China, Canada, Australia, and the European Union.
It has been approved in many countries and regions, and it is also the first Chinese innovative drug approved for marketing in the United States and the European Union
.

References: [1]Zong X, Yu Y, Yang H, et al.
Effects of Gonadotropin-Releasing Hormone Analogs on Ovarian Function Against Chemotherapy-Induced Gonadotoxic Effects in Premenopausal Women With Breast Cancer in China: A Randomized Clinical Trial.
JAMA Oncol Published online December 30, 2021.
doi:10.
1001/jamaoncol.
2021.
6214[2]Spencer Christine N,McQuade Jennifer L,Gopalakrishnan Vancheswaran et al.
Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response.
[J] .
Science, 2021, 374: 1632-1640.
[3]https://mp.
weixin.
qq.
com/s/s-PrYAskQrVU1lp2N17Jwg[4]https://mp.
weixin.
qq.
com/s/GKzMIfme06jalI4oDHpJmQ