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Cediranib is a pan-vascular endothelial growth factor receptor inhibitor that inhibits the expression of the homologous recombinant repair (HRR) gene and increases sensitivity to polypolymer (ADP-ribose) polymerase inhibition
in preclinical models.
The study aimed to determine whether Cediranib combined with olaparib can improve clinical outcomes
in prostate cancer patients.
Patients with progressive metastatic castration-resistant prostate cancer (mCRPC) were randomized 1:1 to Group A (Cediranib 30 mg once daily, olaparib 200 mg twice daily) or Group B (olaparib 300 mg twice daily).
The primary endpoint was radiographic progression-free survival (rPFS)
in the population intended to treat.
The secondary endpoint was rPFS
in patients with or without HRR deficiency.
Prognosis for treatment in both groups
In the intention-to-treat population (n = 90), the median rPFS in groups A and B was 8.
5 months and 4.
0 months
, respectively.
Compared with olaparib alone, Cediranib/olaparib significantly increased the rPFS rate (HR 0.
617, p=0.
0359).
Subgroup analysis showed that among HRR-deficient mCRPC patients, the median rPFS in groups A and B was 10.
6 months and 3.
8 months, respectively (HR 0.
64); In patients with BRCA2-mutated mCRPC, the median rPFS in groups A and B was 13.
8 and 11.
3 months
, respectively.
The incidence of grade 3 to 4 adverse events in groups A and B was 61% and 18%,
respectively.
In summary, Cediranib combined with olaparib significantly prolongs the radiographic progression-free survival of patients with metastatic castration-resistant prostate cancer
compared with olaparib alone.
This joint regimen was associated with
an increased incidence of grade 3 to 4 adverse events.
Patients in the BRCA2 mutant subgroup had a relatively long
median rPFS regardless of whether they were treated with olaparib plus Cediranib or orapalib alone.
Original source:
Joseph W.
Kim, et al.
Randomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The Results From National Cancer Institute 9984.
Journal of Clinical Oncology.
October 17, 2022.
https://ascopubs.
org/doi/full/10.
1200/JCO.
21.
02947.
