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A post-hoc analysis of the phase-3 LATITUDE study assessed the impact of abiraterone acetate plus prednisone (AA+P) on overall survival (OS) and radiographic progression-free survival (rPFS) in men with metastatic castration-sensitive prostate cancer (mCSPC) and visceral metastases (VM). Newly diagnosed mCSPC patients were randomized (1:1) to AA+P and androgen deprivation therapy (ADT) or placebo+ADT. Patients with VM in liver or lungs with or without other soft tissue and bone metastases (based on CT/MRI) at baseline were analyzed, after 51.8 months' median follow-up. Co-primary endpoints, OS and rPFS, were analyzed. Among 1199 patients enrolled, 228 (19%) had VM at baseline (114 each in AA+P and placebo groups), of which 53 (23.2%; AA+P = 29, Placebo = 24) had liver metastases and 117 (51.3%; AA+P = 60, Placebo = 57) had lung metastases. In patients with VM, treatment with AA+P versus placebo showed an improvement in OS (median 55.4 vs 33.0 months; HR = 0.582; 95%CI = 0.406–0.835; P = 0.0029) and rPFS (median 30.7 vs 18.3 months; HR = 0.527; 95%CI = 0.366–0.759; P = 0.0005), comparable to that of patients without VM. AA+P versus placebo in lung metastases patients was associated with greater improvement in OS (HR = 0.60; 95%CI = 0.35–1.04; P = 0.0678) than in liver metastases patients (HR = 0.82; 95%CI = 0.41–1.66; P = 0.5814). AA+P versus placebo showed improvement in rPFS in lung metastases patients (HR = 0.50; 95%CI = 0.29–0.89; P = 0.0157), but not in liver metastases patients (HR = 1.05; 95%CI = 0.53–2.09; P = 0.8970). AA+P treatment improved both rPFS and OS in men with mCSPC and visceral disease, especially those with lung metastases. Men with liver metastases had a poorer prognosis and their optimal treatment remains to be defined. ClinicalTrials.gov, number NCT01715285 • AAP+ADT showed survival benefit in mCSPC men regardless of visceral disease status. • Men with liver metastases had a poorer prognosis than those with lung metastases. • A benefit in OS and rPFS was not seen in the small group of men with liver metastases. [ABSTRACT FROM AUTHOR]

Abstract: Background: Everolimus (EVE; an inhibitor of mammalian target of rapamycin [mTOR]) enhances treatment options for postmenopausal women with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2–) advanced breast cancer (ABC) who progress on a non-steroidal aromatase inhibitor (NSAI). This is especially true for patients with visceral disease, which is associated with poor prognosis. The BOLERO-2 (Breast cancer trial of OraL EveROlimus-2) trial showed that combination treatment with EVE and exemestane (EXE) versus placebo (PBO)+EXE prolonged progression-free survival (PFS) by both investigator (7.8 versus 3.2months, respectively) and independent (11.0 versus 4.1months, respectively) central assessment in postmenopausal women with HR+, HER2– ABC recurring/progressing during/after NSAI therapy. The BOLERO-2 trial included a substantial proportion of patients with visceral metastases (56%). Methods: Prespecified exploratory subgroup analysis conducted to evaluate the efficacy and safety of EVE+EXE versus PBO+EXE in a prospectively defined subgroup of patients with visceral metastases. Findings: At a median follow-up of 18months, EVE+EXE significantly prolonged median PFS compared with PBO+EXE both in patients with visceral metastases (N =406; 6.8 versus 2.8months) and in those without visceral metastases (N =318; 9.9 versus 4.2months). Improvements in PFS with EVE+EXE versus PBO+EXE were also observed in patients with visceral metastases regardless of Eastern Cooperative Oncology Group performance status (ECOG PS). Patients with visceral metastases and ECOG PS 0 had a median PFS of 6.8months with EVE+EXE versus 2.8months with PBO+EXE. Among patients with visceral metastases and ECOG PS ⩾1, EVE+EXE treatment more than tripled median PFS compared with PBO+EXE (6.8 versus 1.5months). Interpretation: Adding EVE to EXE markedly extended PFS by ⩾4months among patients with HR+ HER2– ABC regardless of the presence of visceral metastases. Funding: Novartis. [Copyright &y& Elsevier]

The efficacy of fulvestrant (Faslodex™), a novel oestrogen receptor (ER) antagonist that downregulates the ER and has no known agonist effects, was compared with the aromatase inhibitor anastrozole (Arimidex™) for the second-line treatment of advanced breast cancer in postmenopausal women with visceral and non-visceral metastases. Assessment was by means of a retrospective subgroup analysis of combined data from two randomised, phase III trials. Objective response (OR) rates were similar in patients treated with fulvestrant and anastrozole, respectively (21.9% versus 19.3%—patients with no visceral metastases; 15.7% versus 13.2%—all of the patients with visceral metastases; 18.8% versus 14.0%—patients with visceral metastases only). The proportion of patients with clinical benefit (CB) was also similar between treatments and between subgroups with and without visceral disease. Fulvestrant is at least as effective as anastrozole, providing a valuable treatment option for advanced breast cancer in postmenopausal women with visceral metastases who have failed on prior endocrine therapy. [Copyright &y& Elsevier]