Poly (ADP-Ribose) Polymerase Inhibitors in Patients With Urothelial Cancer.

Poly ADP-ribose polymerase inhibitors (PARPis) have clinical activity in several cancers. The rationale of their therapeutic use in urothelial cancer (UC) resides in the high homologous-recombination repair (HRR) deficiency (HRD) prevalence and potential cross-sensitivity with platinum-based chemotherapy (PBCT). This review aims to summarize and analyze trials exploring the activity of PARPis in UC, focusing on patients who may benefit from those agents, the best clinical setting for the treatment and the benefit of the association with immune-checkpoint inhibitors (ICIs). We included all the available trials analyzing the activity of PARPis in UC in neoadjuvant, adjuvant, first or subsequent lines, and maintenance setting. We included PARPis in monotherapy and in association with other agents. The results in the maintenance setting are intriguing: ATLANTIS trial showed signals of improved progression-free survival in patients with known HRR aberrations, although the Meet-URO12 trial, with its negative results, suggested the failure of clinical selection based on platinum sensitivity only. Single-agent PARPis in pretreated patients showed discouraging results in an unselected population of chemo-refractory patients. Concerning the association of PARPis with ICIs, several trials are exploring their role in platinum-naïve setting; the results in the advanced setting were globally negative. Prior selection of HRD status is essential to identify patients who might benefit from PARPis. The ideal clinical settings seem to be the maintenance treatment and the combination with ICIs in platinum-naïve patients. Definitive results of ongoing and further trials will delineate the position for PARPis, if any, in UC therapy.

Frequency of Germline and Somatic BRCA1 and BRCA2 Mutations in Prostate Cancer: An Updated Systematic Review and Meta-Analysis.

In prostate cancer (PC), the presence of BRCA somatic and/or germline mutation provides prognostic and predictive information. Meta-analysis aims to estimate the frequency of BRCA mutations in patients with PC (PCp). In November 2022, we reviewed literature searching for all articles testing the proportion of BRCA mutations in PCp, without explicit enrichment for familiar risk. The frequency of germline and somatic BRCA1 and/or BRCA2 mutations was described in three stage disease populations (any/metastatic/metastatic castration-resistant PC, mCRPC). Out of 2253 identified articles, 40 were eligible. Here, 0.73% and 1.20% of any stage PCp, 0.94% and 1.10% of metastatic PCp, and 1.21% and 1.10% of mCRPC patients carried germline and somatic BRCA1 mutation, respectively; 3.25% and 6.29% of any stage PCp, 4.51% and 10.26% of metastatic PCp, and 3.90% and 10.52% of mCRPC patients carried germline and somatic BRCA2 mutation, respectively; and 4.47% and 7.18% of any stage PCp, 5.84% and 10.94% of metastatic PCp, and 5.26% and 11.26% of mCRPC patients carried germline and somatic BRCA1/2 mutation, respectively. Somatic mutations are more common than germline and BRCA2 are more common than BRCA1 mutations; the frequency of mutations is higher in the metastatic setting. Despite that BRCA testing in PC is now standard in clinical practice, several open questions remain.

Clinical value of offering multiple chemotherapy lines to a luminal-like metastatic breast cancer: A case report with eribulin.

INTRODUCTION: The achievement of complete response with chemotherapy after multiple treatment lines in metastatic breast cancer and the chemosensitivity in a luminal-like breast cancer are two important issues as it is often asked whether there is a potential limit to the number of therapeutic lines offered and what clinical value they may have. In this setting, eribulin mesylate is a chemotherapy option available. Several randomized and observational studies demonstrated eribulin's meaningful improvement on prolongation of survival, chronicling the disease and preventing the onset of new metastases, although the rate of complete responses is rather limited. CASE DESCRIPTION: We report the five-year history of a luminal A breast cancer, stage IV at diagnosis, metastasized to bone and brain. After undergoing four chemotherapy lines and several radiotherapy sessions with partial response as the best response on bone and with a complete response on brain, our patient finally achieved a metabolic complete response also on bone after about a year of fifth-line treatment with eribulin. Currently the patient is in close clinical and radiological follow-up. CONCLUSIONS: This case report aims to emphasize the clinical value of a chronic chemotherapy treatment also in heavily pretreated and luminal-like metastatic breast cancer, supporting eribulin as a good choice to consider.

Systematic review of adoption, reporting and impact of health-related quality of life in phase III non-inferiority trials of systemic oncology treatments.

BACKGROUND: Quality of life (QoL) assessment and patient-reported outcomes appear to be crucial in the rationale and interpretation of non-inferiority (NI) trials. The aim of this study was to assess the inclusion of QoL among endpoints in phase III NI oncology trials and the relevance of QoL results in the reporting and interpretation of these studies. MATERIALS AND METHODS: By PubMed search and hand-search of 11 selected journals, we identified phase III NI trials in adult patients affected by solid tumours, published between 2012 and 2021. Trials were classified according to 4 NI strategies: (1) different drugs; (2) alternative drug administration routes; (3) shorter treatment duration; (4) "deintensification" of treatment schedule. Three main endpoints were: (1) the proportion of publications including QoL among endpoints; (2) the proportion of primary publications reporting QoL results; (3) the proportion of trials with available QoL results actually favoring the experimental treatment out of trials declaring NI. RESULTS: 106 publications were eligible. QoL was included among endpoints in 59 studies (55.7%), and QoL results were available in 40 primary publications (37.7%). In the 73 trials testing the NI of different drugs, QoL was included in 43 trials (58.9%) and QoL results were present in 31 publications (42.5%). Among the 74 trials formally demonstrating NI, only 19 trials (25.7%) had QoL results actually supporting the experimental treatment. CONCLUSIONS: In many NI trials in oncology, assessment and reporting of QoL are deficient. Furthermore, most trials formally claiming NI cannot count on QoL results actually supporting the experimental arm.