Abidoye, Oyewale O.

LBA4500 Background: Cisplatin-based chemo is a standard 1L treatment (tx) for mUC and the only tx that prolongs OS; however, age or comorbidities render many pts ineligible, and 30-50% receive no tx. Atezo (MPDL3280A) is active and well tolerated in platinum-treated mUC, justifying testing atezo as 1L tx in cisplatin-ineligible pts. Methods: Pts were chemo naive in the metastatic setting and cisplatin ineligible (renal [GFR > 30 but < 60 mL/min]/hearing impairment, ≥ G2 peripheral neuropathy [PN] or ≥ ECOG PS2). Atezo 1200 mg was given IV q3w until PD (RECIST v1.1). Centrally assessed PD-L1 on tumor infiltrating immune cells (IC; SP142 IHC assay) was scored IC2/3, 1 or 0. The primary efficacy endpoint was confirmed ORR assessed per RECIST v1.1 (central independent review facility) using a data cutoff of Sep 14, 2015. Results: 119 efficacy/safety-evaluable pts of any PD-L1 IC had a median age of 73 y: 21% ≥ 80 y. 18% had prior systemic tx (21% [neo]adjuvant); 10% had radiotherapy. 66% had visceral mets. 71% had CrCl < 60 mL/min; 13% had hearing loss ≥ 25 dB; 6% had prior PN ≥ G2; 20% had ECOG PS2. ORR was 19% (95% CI 13-28; 5% CR), and responses occurred in all IC subgroups (Table; includes DCR/PFS/OS) and in pts with poor prognostic factors. 22/23 responses were ongoing with mDOR not reached. Median follow-up was 8.5 mo (range 0.2-14.3); median tx duration was 15 wk. Atezo was generally well tolerated. Tx-related all-G and G3-4 AEs were seen in 64% and 12% of pts, respectively. Related all-G AEs ≥ 10% included fatigue, pruritus, diarrhea. 1 G5 related AE occurred (sepsis). 3% had a G3-4 immune-mediated AE. Conclusions: Atezo has clinically meaningful activity in 1L cisplatin-ineligible mUC pts, and preliminary OS is encouraging. The durable nature of response and favorable AE profile makes this an attractive alternative to chemo. NCT02108652. Clinical trial information: NCT02108652. [Table: see text]

166 Background: T-DM1 is an antibody-drug conjugate composed of trastuzumab, a stable linker, and the cytotoxic agent DM1. Few T-DM1 data are available in settings approximating clinical practice. We present safety and efficacy data from T-PAS, an expanded access study of T-DM1 in patients (pts) with previously treated HER2-positive MBC. Methods: T-PAS is a US multicenter study of T-DM1 (3.6 mg/kg q3w) in HER2-positive (IHC 3+ or FISH/CISH+) locally advanced or MBC. Key eligibility criteria: prior anthracycline and taxane; prior capecitabine or 5-FU and ≥2 HER2-directed agents (including trastuzumab and lapatinib) for MBC; LVEF ≥50%. Primary endpoint: safety; secondary endpoint: investigator-assessed objective response rate (ORR) in pts with measurable disease. Safety was assessed on day 1 of each cycle; ECHO/MUGA scans were every 12 weeks. Results: This analysis includes 215 pts enrolled in May 2010–Sep 2011 (data cutoff 7/31/2012). Pts received a median of 7 prior systemic MBC therapies (range 1–23) with a median cumulative anthracycline dose of 240 mg/m2(range 6–2645). At baseline, median LVEF was 60% and 50% of pts had investigator-reported cardiovascular disease. Median follow-up was 5.9 months (range 0.1–25.3); median T-DM1 duration was 5.0 months (range 0–23) with 15.8% receiving >18 cycles. ORR was 25.6% (42/164). Rate of grade ≥3 AEs was 43.7% and of SAEs of any grade was 18.1%. Most common all-grade AEs were fatigue (50.7%), nausea (36.3%), and headache (24.2%). Most common grade ≥3 AEs were thrombocytopenia (7.9%), fatigue (4.7%), and increased aspartate aminotransferase and anemia (each 3.7%). There were no grade ≥3 bleeding events. Cardiac dysfunction (primarily asymptomatic decreases in LVEF) was reported in 8 pts (3.7%); 4 were grade ≥3, 3 resulting in T-DM1 discontinuation. Conclusions: In this study that more closely reflects the real-world setting, the safety profile of T-DM1 was similar to that previously reported in conventional clinical trials, with no new safety signals. In this pretreated population (median of 7 prior therapies for HER2-positive MBC), significant activity was observed. Clinical trial information: NCT01120561.