Metronomic cyclophosphamide for bone marrow carcinomatosis in metastatic castration-resistant prostate cancer.

PURPOSE: In some patients with prostate cancer, bone marrow carcinomatosis develops later in the course of the disease, which has a poor prognosis. These are often heavily pretreated patients in the castration-resistant situation for whom there are no other therapeutic options, because either all available systemic therapies have already been used or the use of one is not possible due to the cytopenias associated with bone marrow carcinomatosis. In our literature search, there are no data on this treatment in the setting available, especially no clinical trial or even randomized data. This case series is to determine the clinical efficacy of metronomic cyclophosphamide in patients with metastatic castration-resistant prostate cancer and bone marrow carcinomatosis, particularly with regard to stabilization of the blood count (thrombocytopenias) and thus the possibility of further (more toxic) lines of therapy. METHODS: Retrospective unicenter analysis was performed on eleven patients between 54 and 84 years of age on metronomic cyclophosphamide for bone marrow carcinomatosis in metastatic castration-resistant prostate cancer treated at a Swiss cancer center between 2014 and 2023. RESULTS: Eleven patients received metronomic cyclophosphamide for varying periods of time; the majority had severe cytopenias (especially thrombocytopenias). Partially hematologic stabilization was achieved with administration of further systemic therapies. CONCLUSION: Our case series demonstrates that the use of metronomic cyclophosphamide allows hematologic stabilization for months, benefiting patients who had already received all available therapies for metastatic castration-resistant prostate cancer. Alternatively, it may act as bridging therapy to allow consecutive administration of more toxic therapies with proven survival benefit.

First-line durvalumab in patients with PD-L1 positive, advanced non-small cell lung cancer (NSCLC) with a performance status of 2 (PS2). Primary analysis of the multicenter, single-arm phase II trial SAKK 19/17.

INTRODUCTION: The safety and efficacy of first-line durvalumab in PS2 patients with advanced NSCLC is unknown. Here, we present the primary analysis of first-line durvalumab in PS2 patients, unsuitable for combination chemotherapy. METHODS: In this single-arm, multicenter, phase II trial patients with PD-L1 positive (tumor proportional score ≥25%), advanced NSCLC with PS2, received four-weekly durvalumab 1500 mg. The primary endpoint was overall survival (OS) at 6 months. RESULTS: Forty-eight patients were included. Median follow-up was 23.3 months (95% CI: 14.3-28.6). OS at 6 months was 60% (95% CI: 45-74%). Median OS was 8.5 months (95%CI: 4.4-16.7). Objective response rate and median progression free survival were 17% (95% CI: 8-30%) and 2.5 months (95% CI: 1.8-7.1), respectively. Thirty-three deaths were observed at the time point of the analysis. Seven early fatal events considered not treatment-related occurred during the first 5 weeks of treatment. Four out of the first 7 early fatal events (4/7; 57%) were respiratory failure in patients with advanced symptomatic primary lung tumors. Three more early fatal events occurred after exclusion of patients with grade ≥ 3 dyspnea. Treatment-related AEs ≥G3 were reported in 9 patients (19%) and included colonic perforation in one patient (grade 5), colitis in 4 patients (8%), increased lipase in 3 patients (6%), and hepatitis in 2 patients (4%). CONCLUSIONS: First-line durvalumab in PS2 patients with advanced PD-L1 positive NSCLC results in a high number of early fatal events. When patients with grade ≥ 3 dyspnea are excluded a promising 6-month OS with an acceptable toxicity profile can be observed. Durvalumab could be an option instead of single agent chemotherapy for PS2 patients who are not candidates for platinum doublet chemotherapy provided they are well selected.