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Home Niraparib Maintenance Fails to Improve Survival in Advanced Urothelial Carcinoma Despite DNA Repair-Targeting Mechanism

Niraparib Maintenance Fails to Improve Survival in Advanced Urothelial Carcinoma Despite DNA Repair-Targeting Mechanism

Feb 26, 2022 00:17 CST Updated 00:17
TESARO

Tumor Therapy Developer

GSK

Pharmaceutical R&D Manufacturer

University of Turin

Located in the heart of Turin, Italy—the hub of Europe’s automotive industry—the University of Turin was founded in 1404 and boasts a history spanning over 600 years. As one of the largest universities in Italy, the University of Turin excels in research across fundamental disciplines such as mathematics, chemistry, physics, economics, law, agriculture, medicine, and psychology. Its programs in economics and business administration enjoy widespread acclaim across continental Europe.In the 20th century, the University of Turin emerged as an intellectual center for anti-fascist enlightenment. As Italy’s oldest university, it counts among its distinguished alumni Nobel laureates, Italian political leaders, renowned philosophers, and literary figures. Notable graduates include Nobel laureates Renato Dulbecco and Rita Levi-Montalcini; mathematical giants Joseph-Louis Lagrange and Augustin-Louis Cauchy; philosopher Desiderius Erasmus; economist Vilfredo Pareto; entrepreneur Giovanni Agnelli; scientist Amedeo Avogadro; and writer Italo Calvino.


Bladder Cancer - (Image Source - medscape.com)

News on February 25, 2022 /BioValleyBIOON/ -- According to recent reports at the 2022 American ClinicalTumorResults from the multicenter phase 2 Meet-URO12 trial (NCT03945084) presented at the ASCO Genitourinary Cancers Symposium (ASCO GU),In patients with advanced urothelial carcinoma (UC, the most common type of bladder cancer) whose disease did not progress after first-line chemotherapy, the combination of Zejula (Chinese trade name: Zele, generic name: niraparib) and best supportive care (BSC) did not improve clinical outcomes compared to BSC alone.. The trial was conducted by the University of Turin, Italy, in collaboration with Tesaro (GSKUnder its umbrellaTumorSponsored by TESARO, Inc.,GSKGSK provides Zejula.

The trial enrolled 58 patients with unresectable, locally advanced or metastatic UC. All patients received 4-6 cycles of platinum-based chemotherapy as first-line treatment and showed no evidence of disease progression. These patients were randomized in a 2:1 ratio to receive either Zejula + BSC combination therapy (n=39) or BSC alone (n=19). The gender and median age were similar between the two groups. Overall, the median age was 69.6 years (range: 44.4-84.8), and 74.1% of the patients were male.

The most common sites of disease in the Zejula group were visceral (48.7%) or bone (23.1%), while in the BSC group, the most common sites were visceral (57.9%) or lymph node only (31.6%). Patients in the Zejula group were more likely to have received cisplatin-based therapy (61.5%) compared with those in the BSC alone group (31.6%).

The results showed that, 2The median progression-free survival (PFS) was similar between the treatment groups: 2.1 months in the Zejula+BSC group and 2.4 months in the BSC group (adjusted hazard ratio HR=0.87; 95% CI: 0.46-1.67; p=0.68). The 6-month PFS rate was 28.2% in the Zejula+BSC group and 26.3% in the BSC group.

A total of 47 patients had known molecular profiles, with 21 patients having homologous recombination repair (HRR) mutations, six of whom had known pathogenic HRR mutations. When researchers evaluated only the patients with HRR mutations, there was no difference in median PFS between the treatment groups; it was 2.0 months for both groups. However, this analysis was limited by the small number of patients.

The incidence of Grade 3 or higher treatment-emergent adverse events (TEAEs) was higher in the Zejula+BSC group compared to the BSC group, at 65.8% and 15.8%, respectively.
The most common Grade 3 or higher TEAE in the Zejula+BSC group wereAnemia, thrombocytopenia, and fatigue.

The active pharmaceutical ingredient in Zejula is niraparib, an oral, highly selective poly ADP-ribose polymerase (PARP) inhibitor that exploits deficiencies in DNA repair pathways to preferentially kill cancer cells.This mode of action gives the drug the potential to treat a wide range of tumors with DNA repair defects. PARP is associated with a broadTumorType-related, especiallyBreast CancerAnd ovarian cancer.

Zejula, developed by TESARO, is a potential best-in-class PARP inhibitor due to its differentiated efficacy, once-daily dosing, and superior pharmacokinetic properties, including its ability to cross the blood-brain barrier.

In April 2016, Janssen, a subsidiary of Johnson & Johnson, signed a global (excluding Japan) collaboration and licensing agreement with TESARO, obtaining exclusive rights to Zejula for the treatment of prostate cancer. At the end of September 2016, Zai Lab reached a licensing agreement with TESARO, gaining the rights to Zejula in mainland China, Hong Kong, and Macao. In December 2018, GSK acquired TESARO for $5.1 billion (approximately £4 billion). (Bioon.com)