Up to half of mUC pts are ineligible for cis due to ECOG PS or comorbidities. These pts have been underserved in clinical trials and have a high unmet need. Carboplatin-based regimens are associated with notable toxicity, transient responses and mOS of 6-9 mo. Atezo is effective and tolerable in platinum-treated mUC and was tested in cis-ineligible pts as 1L treatment (tx).
Cis ineligibility criteria included any of: renal impairment (CrCl 30-60 ml/min), hearing loss or peripheral neuropathy ≥ G2 or ECOG PS2 (Table). Pts with no prior tx for mUC (> 12 mo since any perioperative tx) received 1200 mg atezo IV q3w until RECIST v1.1 PD. Primary endpoint was ORR (central review). PD-L1 on immune cells (IC) was centrally scored as IC2/3, 1 or 0 (SP142 IHC assay).
Of 119 evaluable pts, most (70%) had renal impairment. Confirmed ORR was 24%; CR rate was 7%. Responses were durable (21/28 ongoing at the 14 Mar 2016 data cut off), with mDOR not reached at 14.4 mo median follow up (mDOR range 3.7-16.6+). Responses occurred across all IC subgroups, in pts with poor prognostic factors and were enriched in upper tract primary disease (Table). mOS was 14.8 mo in all-comer pts (95% CI 10.1, NE; 47% event:pt ratio). With a median of 15 wk on tx, atezo was well tolerated (6% AE tx withdrawal) with no decline in renal function and a low immune-mediated AE rate. Common (≥ 10%) tx-related AEs were fatigue, pruritus and diarrhea. 1 tx-related G5 AE, sepsis, was seen. Updated OS and efficacy by molecular subtype, mutation load and microsatellite status will be presented.
IMvigor210a Cohort 1: ORR by Baseline Subgroups (All Pts)b