No abstract

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Despite stringent eligibility criteria for trial participation, early discontinuation often occurs in phase I trials. To better identify patients unlikely to benefit from phase I trials, we investigated predictors for early trial discontinuation. Data from 415 patients with solid tumors who participated in 66 trials were pooled for the current analysis. Early trial discontinuation was defined as (i) trial discontinuation within 28 days after start of treatment or (ii) discontinuation before administration of the first dosage in eligible patients. Multilevel logistic regression analyses were conducted to identify predictors for early trial discontinuation. Eighty-two participants (20%) demonstrated early trial discontinuation. Baseline sodium level below the lower limit of normal (OR = 2.95, 95%CI = 1.27–6.84), elevated alkaline phosphatase level >2.5 times the upper limit of normal (OR = 2.72, 95%CI = 1.49–4.99), performance score ≥ 1 (OR = 2.07, 95%CI = 1.03–4.19) and opioid use (OR = 1.82, 95%CI = 1.07–3.08) were independent predictors for early trial discontinuation. Almost 50% of the patients with hyponatremia and all four patients in whom all four predictors were present together discontinued the trial early. Hyponatremia, elevated alkaline phosphatase level, performance score ≥1 and opioid use were identified as significant predictors for early trial discontinuation. Hyponatremia was the strongest predictor and deserves consideration for inclusion in eligibility criteria for future trials.

329 Background: Men with metastatic castration resistant prostate cancer harboring somatic mutant SPOP (mt SPOP) have improved progression free survival (PFS) on abiraterone than those with wild-type SPOP (wt SPOP) (Boysen et al, CCR 2018; PMID: 30068710). We hypothesized that mtSPOP will be associated with improved response to systemic therapy and outcomes in mCSPC. Methods: This retrospective study included patients from 4 academic institutions. Eligibility criteria: receipt of standard androgen deprivation therapy (ADT) without intensification (chemotherapy or novel hormonal agents) for the diagnosis of d-mCSPC, no prior history or treatment for prostate cancer, and established SPOP status determined by targeted next-generation sequencing. PFS was defined per PCWG2 defined PSA or investigator assessed radiographic progression. Overall survival (OS) was calculated from date of starting ADT for d-mCSPC to date of death. Kaplan-Meier analysis and t-test were used to compare variables in these two cohorts. Results: Of 110 mtSPOP men with advanced prostate cancer identified, 37 had d-mCSPC of which 25 received ADT. Of 353 wtSPOP patients, 184 had d-mCSPC of which 97 received ADT. Baseline demographics and disease characteristic were similar (table). mtSPOP was associated with significantly improved PFS [35 vs. 14 months, HR 0.519 (95% CI 0.312-0.861), p=0.011] and OS [97 vs. 69 months, HR 0.4392 (95% CI=0.207-0.931); p=0.032] with ADT as compared to wtSPOP patients. Conclusions: Men with d-mCSPC with somatic mtSPOP have improved outcomes with ADT than those with wtSPOP. Once validated, these hypothesis generating data may aid with counselling and treatment selection, as well as patient stratification in future trials in d-mCSPC.[Table: see text]