A Modular Trial of Androgen Signaling Inhibitor Combinations Testing a Risk-Adapted Strategy in Patients with Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: To determine the efficacy and safety of risk-adapted combinations of androgen signaling inhibitors and inform disease classifiers for metastatic castration-resistant prostate cancers. PATIENTS AND METHODS: In a modular, randomized phase II trial, 192 men were treated with 8 weeks of abiraterone acetate, prednisone, and apalutamide (AAPA; module 1) and then allocated to modules 2 or 3 based on satisfactory (≥50% PSA decline from baseline and <5 circulating tumor cell/7.5 mL) versus unsatisfactory status. Men in the former were randomly assigned to continue AAPA alone (module 2A) or with ipilimumab (module 2B). Men in the latter group had carboplatin + cabazitaxel added to AAPA (module 3). Optional baseline biopsies were subjected to correlative studies. RESULTS: Median overall survival (from allocation) was 46.4 [95% confidence interval (CI), 39.2-68.2], 41.4 (95% CI, 33.3-49.9), and 18.7 (95% CI, 14.3-26.3) months in modules 2A (n = 64), 2B (n = 64), and 3 (n = 59), respectively. Toxicities were within expectations. Of 192 eligible patients, 154 (80.2%) underwent pretreatment metastatic biopsies. The aggressive-variant prostate cancer molecular profile (defects in ≥2 of p53, RB1, and PTEN) was associated with unsatisfactory status. Exploratory analyses suggested that secreted phosphoprotein 1-positive and insulin-like growth factor-binding protein 2-positive macrophages, druggable myeloid cell markers, and germline pathogenic mutations were enriched in the unsatisfactory group. CONCLUSIONS: Adding ipilimumab to AAPA did not improve outcomes in men with androgen-responsive metastatic castration-resistant prostate cancer. Despite the addition of carboplatin + cabazitaxel, men in the unsatisfactory group had shortened survivals. Adaptive designs can enrich for biologically and clinically relevant disease subgroups to contribute to the development of marker-informed, risk-adapted therapy strategies in men with prostate cancer.

Prognostic value of the Memorial Sloan Kettering Prognostic Score in metastatic pancreatic adenocarcinoma.

BACKGROUND: The Memorial Sloan Kettering Prognostic Score (MPS), a composite of the neutrophil-lymphocyte ratio (NLR) and albumin, is an objective prognostic tool created as a more readily available alternative to the Glasgow Prognostic Score. A prior analysis of patients with metastatic pancreatic adenocarcinoma (mPDAC) suggested that the MPS may predict survival, although it did not control for clinically relevant factors. METHODS: MPS scores were calculated for patients with mPDAC treated at Memorial Sloan Kettering Cancer Center from January 1, 2011, to December 31, 2014. An MPS scale of 0 to 2 was used: 0 for an albumin level ≥ 4 g/dL and an NLR ≤ 4 g/dL, 1 for either an albumin level < 4 g/dL or an NLR > 4 g/dL, and 2 for an albumin level < 4 g/dL and an NLR > 4 g/dL. Performance status, antineoplastic therapy, presence of thromboembolism (TE), radiation therapy, and metastatic sites were also analyzed. The associations with overall survival were examined with time-dependent Cox proportional hazards regression analyses. RESULTS: A multivariate model revealed that higher MPS scores at diagnosis (hazard ratio for MPS of 2 vs MPS of 0, 1.41; 95% confidence interval, 1.13-1.76), liver metastases, radiation therapy, hospital admissions, TE, and performance status were associated with worse overall survival. The median overall survival for patients with MPS scores of 0, 1, and 2 were 12.9, 9.0, and 5.4 months, respectively. CONCLUSIONS: The MPS, an easily calculated composite of the NLR and albumin, is an objective tool that may predict survival in mPDAC independently of performance status, disease characteristics, and cancer therapy. LAY SUMMARY: The Memorial Sloan Kettering Prognostic Score (MPS) is a new scoring system that incorporates markers of inflammation found in individuals' blood at the diagnosis of metastatic pancreatic cancer. Data suggest that the MPS may help to determine prognosis.

Mechanical Thrombectomy for Submassive Pulmonary Embolism in an Adult with Duodenal Adenocarcinoma and Brain Metastases.

A 52-year-old African American man with small bowel adenocarcinoma metastatic to the brain and leptomeninges was found to have an acute pulmonary embolism while hospitalized for acute lower limb weakness, bowel, and urinary incontinence. He had an elevated troponin, echocardiographic findings concerning for right heart failure, and bilateral segmental and subsegmental pulmonary artery perfusion deficits with right pulmonary artery thrombus on CT angiography. Given the laboratory and radiographic findings with normotensive blood pressure, the patient was diagnosed with a submassive pulmonary embolism.  After deliberation with interventional radiology and hematology, the patient underwent mechanical thrombectomy and was treated with therapeutic anticoagulation. Mechanical thrombectomy revealed substantial clot burden in the central pulmonary arteries and yielded a significant improvement in hypoxia and dyspnea.  This case was an excellent exercise in therapeutic decision-making amidst a dynamic disease process that required integration of numerous clinical and diagnostic data points, including empiric anticoagulation with high clinical suspicion of acute pulmonary embolism, review of contraindications to anticoagulation and thrombolysis in metastatic malignancy, and the decision to pursue mechanical thrombectomy in the setting of contraindications to catheter-directed thrombolysis.