Citations

5029 Background: Pembro had activity as monotherapy in pretreated advanced mCRPC. Data are presented here from cohort B (pembro + docetaxel/prednisone) of KEYNOTE-365 (NCT02861573), a phase 1b/2 umbrella study to test combinations in mCRPC. Methods: Pts who progressed on or became intolerant to ≥4 wk of abi or enza in the prechemotherapy mCRPC state and progressed within 6 mo before screening were eligible. Pts received pembro 200 mg IV with docetaxel 75 mg/m2 IV Q3W plus prednisone 5 mg orally twice daily. The primary end points were safety and PSA response rate (confirmed PSA decrease ≥50%). Key secondary end points were 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 y; visceral disease, 36%; measurable disease, 50%) began pembro + docetaxel. Median (95% CI) follow-up was 10 (8-12) mo. Efficacy is outlined in the table. 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 from treatment-related AEs (pneumonitis). Most commonly reported immune-mediated AEs were infusion-related reactions (11%) and colitis (10%). Conclusions: Pembro + docetaxel/prednisone has activity in pts with mCRPC who previously progressed on second-generation hormone therapy. AEs were considered mild for the treatment combination. Clinical trial information: NCT02861573. [Table: see text]

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]

Objective To investigate the association between smoking status and pathological response to cisplatin‐based neoadjuvant chemotherapy ( NAC ) and survival outcomes in patients with muscle‐invasive bladder cancer ( MIBC ) treated with radical cystectomy ( RC ). Patients and Methods We reviewed 201 patients treated with NAC and RC for cT 2– cT 4N0M0 BC between 01/1999 and 01/2015. Smoking status was categorised as: ‘never', ‘former', and ‘current' smoker. Pathological response to NAC was defined as: complete (ypT0N0), partial (ypTis/Ta/T1, N0), and no response (ypT2–4 or ypN+). Clinicopathological characteristics were analysed according to smoking status. Logistic regression analyses tested the association between smoking status and pathological response to NAC . Cox regression analyses tested risk factors associated with recurrence, overall ( OM ) and cancer‐specific mortality ( CSM ). Results Overall, there were 58 (28.9%) never smokers, 87 (43.3%) former smokers, and 56 (27.9%) current smokers. No response to NAC was more frequently noted in current smokers (73.2%; P = 0.007). Former smoker ( odds ratio [OR] 2.28; P = 0.024) and current smoker statuses ( OR 4.52; P < 0.001) were significantly associated with no response to NAC , after adjusting for age, gender, Charlson Comorbidity Index, and clinical stage. Similarly, current smoking status ( hazard ratio [HR] 2.14; P = 0.03) and extravesical pathological tumour stage ( HR 3.31; P < 0.001) were independently associated with an increased risk of recurrence after RC . Conclusion Cigarette smoking was significantly associated with adverse pathological response to cisplatin‐based NAC in patients with MIBC treated with RC . Current smokers were at significantly higher risk of disease recurrence as compared to former and never smokers.