Introduction and Objectives: First-line (1L) treatment (tx) for mUC includes cisplatin (cis)- or carboplatin (carbo)-based chemotherapy or checkpoint inhibitors, depending on patient (pt)- and tumour-specific factors. IMvigor130 is a Phase 3, global, randomised, study of atezo (anti–PD-L1) alone or +PBC vs placebo+PBC in untreated mUC.
Materials and Methods: 1213 PBC-eligible mUC pts were enrolled. Randomisation was 1:1:1 to Arm A (atezo+PBC [gemcitabine (gem) + either cis or carbo]), Arm B (atezo) or Arm C (placebo+PBC). Gem 1000 mg/m2 IV was given on D1 and 8, carbo AUC 4.5 IV or cis 70 mg/m2 IV on D1 and atezo/placebo or atezo 1200 mg IV on D1 of each 3-wk tx cycle. Tumours were assessed at baseline and every 9 wk until INV-assessed PD per RECIST 1.1 or other events. Coprimary endpoints are INV-assessed PFS and OS (Arm A vs C) and OS (Arm B vs C, hierarchical approach) per RECIST 1.1.
Results: Median final PFS was 8.2 vs 6.3 mo in Arm A vs C (HR, 0.82 [95% CI: 0.70-0.96]; P=0.007). The comparison of OS did not cross the prespecified interim efficacy boundary, with a median of 16.0 mo in Arm A and 13.4 mo in Arm C (HR, 0.83 [95% CI: 0.69-1.00]; P=0.027; Table). The median OS for Arm B vs C ITT pts was 15.7 vs 13.1 mo, respectively (HR, 1.02 [95% CI: 0.83-1.24]), and not estimable vs 17.8 mo, respectively (HR, 0.68 [95% CI: 0.43-1.08]), for Arm B vs C PD-L1 IC2/3 pts. ORRs were 47%, 23% and 44% and CR rates were 13%, 6% and 7% for Arms A, B and C, respectively. Tx withdrawal due to AEs occurred in 34%, 6% and 34% of pts in Arms A, B and C, respectively.
Conclusions: Atezo+PBC prolonged PFS vs PBC alone in untreated 1L mUC pts. The combination safety profile was consistent with that of atezo and PBC alone.
Formally Testeda Coprimary Endpoints
|
|
Arm A
Atezo+PBC
n=447
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Arm C
Placebo+PBC
n=397
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Median PFS
95% CI, mo
|
8.2
6.5-8.3
|
6.3
6.2-7.0
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HR
95% CI P valueb
|
0.82
0.70-0.96
0.007
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Median OS
95% CI, mo
|
16.0
13.9-18.9
|
13.4
12.0-15.2
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HR
95% CI P valueb
|
0.83
0.69-1.00
0.027
|
Median follow-up = 11.8 mo
Stratification factors: tumour-infiltrating immune cell (IC) PD-L1 status (IC0 vs IC1 vs IC2/3), Bajorin risk factors/liver mets (0 vs 1 vs 2 or pts with liver mets), investigator-specified PBC (gem+carbo vs gem+cis)
Data cutoff: 31 May 2019
a PFS and OS for Arm A vs C were formally tested with type I error control for multiple comparisons with a prespecified interim efficacy boundary P value of 0.007; Arm B vs C in ITT and PD-L1 IC2/3 pts were not formally tested
b 1-sided P value
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