Giuseppa Scandurra

Trabectedin maintenance therapy after liposomal doxorubicin plus trabectedin combination in patients with relapsed ovarian cancer: the randomized, phase II TRAMANT study

TRAMANT was a multicenter, randomized phase II study assessing the non-inferiority of trabectedin (TRB) as maintenance therapy in patients with relapsed ovarian cancer who responded to initial treatment with pegylated liposomal doxorubicin (PLD) + TRB. Patients with partially platinum-sensitive recurrent ovarian cancer, defined by a platinum-free interval of 6-12 months, were randomly assigned to receive either TRB alone or continued combination therapy. The primary endpoint was progression-free survival, with secondary endpoints including overall survival, objective response rate, and quality of life assessments. Sixty-seven patients were enrolled (median age, 59 years; range; 41-74); most had International Federation of Gynecology and Obstetrics stage III disease (70%) and high-grade serous carcinoma (85%). The median time to recurrence after prior platinum therapy was 8.5 months (range; 6-12), and the median follow-up was 24 months (range; 6-44). Patients received a median of 6 cycles in both arms. Median progression-free survival was 9.8 months with TRB and 16.6 months with PLD + TRB; overall survival was comparable (19.1 vs 23.8 months). Grade 3-4 adverse events occurred in 21% (TRB) and 17% (PLD + TRB), with neutropenia and anemia being the most common toxicities. The results suggest that TRB may be a viable maintenance option for patients with relapsed ovarian cancer, providing a sustained response with favorable tolerability. Nonetheless, the small sample size underscores the need for further research to validate these findings. Studies with larger cohorts are necessary to confirm these results and optimize treatment strategies for recurrent ovarian cancer.

Real-World Analysis of HRD Assay Variability in High-Grade Serous Ovarian Cancer: Impacts of BRCA1/2 Mutation Subtypes on HRD Assessment

The HRD (Homologous Recombination Deficiency) test is considered a genomic alteration useful for guiding therapeutic decisions in patients with ovarian cancer. Some commercial and in house alternative “academic” tests are available. Recent findings indicate that not all BRCA1/2 mutations determine the magnitude of HRD and that some patients carrying BRCA1/2 mutations may exhibit indeterminate or even negative HRD scores. Furthermore, certain therapies (e.g., olaparib and bevacizumab) offer particularly pronounced benefits for high-grade serous ovarian cancer (HGSOC) patients harboring mutations in the DNA-binding domain (DBD) of BRCA1/2. The aim of the present study is to investigate the relationship between the HRD scores and BRCA1/2 status of 51 HGSOC patients (50 BRCA1/2 mutated and 1 wild type). The HRD status was assessed by means of shallow whole-genome sequencing and BRCA1/2 status by the NGS pipeline. We did not find a correlation between the HRD status and type of BRCA1/2 alterations. A strong correlation between the HRD score and age was found. Our paper underlines the need to introduce other biological factors within the algorithms of the HRD evaluation in order to better tailor the HRD status, harmonize the metrics of the HRD assessment, and personalize therapies.

Identification of the novel BRCA1 c.2463_2464delTA mutation in two high grade serous ovarian cancer sisters and potential dosage effects implications: a case report

Ovarian Cancer is one of the leading causes of cancer death among women worldwide and the therapeutic landscape to treat it is constantly evolving. One of the major points of decision for the treatment choice is the presence of some genomic alterations that could confer sensitivity to the new available therapies including inhibitors of poly (ADP-ribose) polymerase (PARPi) with BRCA1 and 2 genes playing the most important role. We performed the search for any somatic and/or germline alteration in patient's samples by next generation sequencing (NGS). On two patients, our bioinformatic tools allowed us to correctly classify the c.2463_2464delTA BRCA1 new variant. The novel BRCA1 c.2463_2464delTA variant which falls into the DNA Binding Domain (DBD) of the BRCA1 gene can be considered as a variant of clinical significance due to the peculiar family and personal history of patients.