Sridhar, Srikala S

170 Background: Pembro had antitumor activity as monotherapy in pretreated advanced mCRPC (KEYNOTE-028; KEYNOTE-199). KEYNOTE-365 (NCT02861573) is a phase 1b/2 umbrella study testing combinations in mCRPC; we report early results from cohort B combining pembro + docetaxel in mCRPC. Methods: Pts who failed or became intolerant to ≥4 weeks of abi or enza in the pre-chemotherapy mCRPC state received pembro 200 mg IV with docetaxel 75 mg/m2 IV Q3W plus prednisone 5 mg orally twice daily. Pts also progressed within 6 months prior to screening as determined by either PSA progression or radiologic progression in bone or soft tissue. Response was evaluated by PSA levels Q3W and imaging Q9W for first year and Q12W thereafter. Primary end points: safety and PSA response rate (confirmed PSA decline ≥50%). Key secondary end points: investigator-determined ORR (RECIST v1.1), disease control rate (DCR: CR+PR+SD ≥6 mo), time to PSA progression, rPFS, and OS. Results: 72 pts (median age 68 years; PD-L1+ 29%; visceral disease 36%; measurable disease 50%) initiated pembro + docetaxel. Median (95% CI) follow-up was 10 (8-12) mo. Efficacy is outlined in table below. Treatment-related AEs occurred in 69 (96%) pts; most frequent (≥30%) were alopecia (43%), fatigue (40%), and diarrhea (39%). Grade 3-5 treatment-related AEs occurred in 27 (38%) pts, including 2 deaths due to treatment-related AEs (pneumonitis). Conclusions: Combination of pembro + docetaxel/prednisone has activity in pts with mCRPC previously failing anti-hormonal therapy. Observed safety profile for the combination was consistent with known safety profile of each component. Clinical trial information: NCT02861573. [Table: see text]

e16003 Background: Multidisciplinary management improves complex treatment decision making in cancer care, but its impact for bladder cancer (BC) has not been documented. While radical cystectomy (RC) is currently viewed as the standard of care for muscle-invasive bladder cancer (MIBC), radiotherapy-based, bladder-sparing trimodal therapy (TMT) combining transurethral resection of bladder tumor, chemotherapy for radiation sensitization and external beam radiotherapy has emerged as a valid treatment option. In the absence of randomized studies, we compared the oncological outcomes between patients managed by RC or TMT using a propensity-score matched cohort analysis. Methods: Patients seen in our multidisciplinary bladder cancer clinic (MDBCC) from 2008 to 2013 were retrospectively reviewed. Those who received TMT for MIBC were identified and matched (for gender, cT and cN stage, ECOG status, Charlson comorbidity score, treatment date, age, CIS, hydronephrosis) using propensity scores, to patients who underwent RC. Overall survival and disease-specific survival (DSS) were assessed with Cox Proportional hazards modeling and competing risk analysis, respectively. Results: 112 patients with MIBC were included after matching, 56 treated with TMT and 56 by RC. Median age was 68.0 years and 29.5% were cT3/cT4. At a median follow up of 4.51 years, there were 20 (35.7%) deaths (13 from BC) in the RC group and 22 (39.3%) deaths (13 from BC) in the TMT group. 5 year DSS was 73.2% and 76.6%, in the RC and TMT groups, respectively (p = 0.49). Salvage cystectomy was performed in 6/56 TMT patients (10.7%). Conclusions: In the setting of a MDBCC, TMT yielded survival outcomes similar to matched RC patients. Appropriately selected MIBC patients should be offered the opportunity to discuss various treatment options including organ-sparing TMT.

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]

Purpose This trial assessed the efficacy and safety of docetaxel monotherapy or docetaxel in combination with ramucirumab (vascular endothelial growth factor receptor 2 antibody) or icrucumab (vascular endothelial growth factor receptor 1 antibody) after progression during or within 12 months of platinum-based regimens for patients with locally advanced or metastatic urothelial carcinoma. Patients and Methods Patients were randomly assigned (1:1:1) to receive docetaxel 75 mg/m2 intravenously (IV) on day 1 of a 3-week cycle (arm A), docetaxel 75 mg/m2 IV plus ramucirumab 10 mg/kg IV on day 1 of a 3-week cycle (arm B), or docetaxel 75 mg/m2 IV on day 1 plus icrucumab 12 mg/kg IV on days 1 and 8 of a 3-week cycle (arm C). Treatment continued until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression-free survival (PFS). Results A total of 140 patients were randomly assigned and treated in arms A (n = 45), B (n = 46), or C (n = 49). PFS was significantly longer in arm B compared with arm A (median, 5.4 months; 95% CI, 3.1 to 6.9 months v 2.8 months; 95% CI, 1.9 to 3.6 months; stratified hazard ratio, 0.389; 95% CI, 0.235 to 0.643; P = .0002). Arm C did not experience improved PFS compared with arm A (1.6 months; 95% CI, 1.4 to 2.9; stratified hazard ratio, 0.863; 95% CI, 0.550 to 1.357; P = .5053). The most common grade 3 or worse adverse events (arms A, B, and C) were neutropenia (36%, 33%, and 39%), fatigue (13%, 30%, and 20%), febrile neutropenia (13%, 17%, and 6.1%), and anemia (6.7%, 13%, and 14%, respectively). Conclusion The addition of ramucirumab to docetaxel met the prespecified efficacy end point for prolonging PFS in patients with locally advanced or metastatic urothelial carcinoma receiving second-line treatment and warrants further investigation in the phase III setting.