Although some patients with Platinum-pretreated metastatic urothelial cancer ( mUC ) demonstrated good responses to Nivolumab monotherapy, the response rate and survival were higher with combined Nivolumab ( Opdivo ) plus Ipilimumb ( Yervoy ) therapy.
CheckMate 032 was a multicentre, open-label study evaluating Nivolumab monotherapy and two dose levels of combined Nivolumab and Ipilimumab.
Patients with previously treated locally advanced or metastatic urothelial cancer, RECIST v1.1 measurable disease, and ECOG performance status less than or equal to 1 were enrolled; most patients had been heavily pretreated.
Seventy-eight patients were treated with Nivolumab monotherapy at 3 mg/kg, 104 received Nivolumab at 3 mg/kg plus 1 mg/kg Ipilumumab for up to 4 doses followed by Nivolumab 3 mg/kg, and 92 patients received 1 mg/kg Nivolumab plus 3 mg/kg Ipilimumab for up to 4 doses followed by Nivolumab 3 mg/kg.
The primary endpoint in the trial was investigator-assessed objective response rate ( ORR ) per RECIST v1.1 with duration of response ( DoR ). Secondary endpoints included investigator- assessed progression-free survival ( PFS ), overall survival ( OS ), and safety.
The data presented at ESMO 2018 Congress were after a minimum follow-up of of 37.7 months for the Nivolumab monotherapy, 38.8 months for the Nivolumab 3 mg/kg / Ipilimumab 1 mg/kg arms, and after a minimum of 7.9 months for the Nivolumab 1 mg/kg / Ipilimumab 3 mg/kg cohort.
The ORR per investigator was 26% ( 95% confidence interval [ CI ], 16 - 37% ), 27% ( 95% CI, 19-37% ), and 38% ( 95% CI, 28-49% ), respectively.
The median DoR was 30.5 ( 95% CI, 8.3 – not estimable [ NE ] ), 22.3 ( 95% CI, 12.8 - NE ), and 22.9 ( 95% CI, 9.8 - NE ) months, respectively.
In the respective treatment arms, median progression-free survival was 2.8 ( 95% CI, 1.5-5.3 ), 2.6 ( 95% CI, 1.4-3.9 ), and 4.9 ( 95% CI, 2.7-6.6 ) months, and median overall survival was 9.9 ( 95% CI, 7.3-21.1 ), 7.4 ( 95% CI, 5.6-11.0 ), and 15.3 ( 95% CI, 10.1-27.6 ) months.
The response was highest in patients with tumour cell expression of PD-L1 greater than or equal to 1%, especially at the Nivolumab 1 mg/kg / Ipilimumab 3 mg/kg dose.
The overall response rate in patients with PD-L1 greater than or equal to 1% was 27% ( 95% CI, 12-48% ), 35% ( 95% CI, 19-55% ), and 58% ( 95% CI, 39-76% ) in the Nivolumab 3 mg/kg, Nivolumab 3 mg/kg / Ipilimumab 1 mg/kg, and Nivolumab 1 mg/kg / Ipilimumab 3 mg/kg arms, respectively.
By contrast, in patients with PD-L1 less than 1%, the ORR was 26% ( 95% CI, 14 – 41% ), 25% ( 95% CI, 14-38% ), and 24% ( 95% CI, 12-40% ) with the respective treatments.
In the overall patient population, grades 3-4 treatment-related adverse events ( TRAEs ) occurred in 27%, 31%, and 39% of patients in the respective treatment arms.
Grade 5 TRAEs of pneumonitis were reported in one patient in the Nivolumab monotherapy arm and one patient in the Nivolumab 3 mg/kg / Ipilimumab 1 mg/kg arm.
A trend toward a higher ORR and longer PFS and OS compared with previous reports of PD-1/PD-L1 monotherapies was observed with the combination of Nivolumab 1mg/kg / Ipilumumab 3 mg/kg in this PD-L1 unselected population.
The combination had a manageable safety profile.
These results support the ongoing phase III CheckMate 901 trial of Nivolumab 1 mg/kg plus Ipilimumab 3 mg/kg compared to standard chemotherapy in patients with previously untreated metastatic urothelial cancer. ( Xagena )
Source: European Society of Medical Oncology - ESMO Congress, 2018