Laura Vertechy

Real-life observational study on niraparib in older patients with primary tubo-ovarian cancer: a focus on safety and efficacy

Abstract Background Niraparib is approved for maintenance treatment of tubo-ovarian cancer patients, but data on older patients are limited. This retrospective study evaluated its safety and efficacy in primary advanced tubo-ovarian cancer, focusing on patients ≥ 75 years. Methods Women aged ≥ 50 years diagnosed with primary high-grade serous tubo-ovarian cancer, treated with niraparib between 2019–2023, were enrolled. Patients were stratified into three groups: A (50–64 years), B (65–74 years), and C (≥ 75 years). The primary outcome was progression-free survival. The secondary outcomes were toxicity and dose reduction. Results 127 patients were identified: 62 (48.8%) group A, 26 (20.5%) group B, and 39 (30.7%) group C. Baseline characteristics were comparable across groups, excluding a higher proportion of interval cytoreductive surgeries ( p  = 0.001), residual tumor ( p  = 0.01) and Eastern Cooperative Oncology Group (ECOG) > 1 ( p  = 0.01) in group C. Most patients started niraparib at 200 mg/day with dose reductions primarily occurred within fourth cycle. Dose reductions were observed in 77.4%, 69.2% and 56.4% of patients in groups A, B, and C, respectively ( p  = 0.08). In patients ≥ 75 years, 26 (66.7%) discontinued treatment due to disease progression (48.7%) or toxicity (17.9%). There were no significant differences in common or grade ≥ 3 adverse events between groups. Progression-free survival was 12 months (95%CI: 2.0–25.0) for group A, 29 months (95%CI: 11.0–52.0) for group B, and 16 months (95%CI: 1.0–31.0) for group C ( p  = 0.78). Conclusions Our findings suggest that niraparib is safe and well-tolerated in aged ≥ 75 years. Concerns about toxicity should not preclude the enrollment of elderly patients in treatment regiments.

Failure of early interval debulking surgery after standard neoadjuvant chemotherapy: May bevacizumab add something? A large retrospective study

Data are limited on the use of bevacizumab in neoadjuvant setting for High-Grade Serous ovarian Cancer (HGSC) patients. This study explores the effect of adding bevacizumab to standard neoadjuvant chemotherapy (NACT) following the failure of early Interval Debulking Surgery (eIDS). This monocentric study retrospectively enrolled FIGO stage IIIC-IV HGSC patients (2017-2021), persisting unresectable after three NACT cycles. Eligible patients had an ECOG performance status ≤2, were aged 40-75 years, and had no contraindications to bevacizumab administration. Patients were stratified whether they added bevacizumab from cycles 4 to 6 (CPB group) or not (CP group). The primary endpoint was the cytoreduction rate after six cycles (delayed IDS, dIDS). Overall, 58(23 %) patients received neoadjuvant bevacizumab(CPB), and 190 (77 %) did not (CP). Delayed IDS was performed in 117(47.6 %) patients (CPB:31-53.4 %; CP:86-45.8 %; p = 0.38), with complete gross resection rates of 83.9 % and 88.5 %, respectively (p = 0.72). Severe postoperative complications were comparable (CP: 8 %, CPB: 9.7 %, p = 0.069). Median overall survival (OS) for dIDS patients showed no significant difference (CPB: not reached, CP:38 months, p = 0.55), nor did progression-free survival (PFS; CPB:14 months, CP:12 months, p = 0.830). Conversely, among 130(52 %) patients persisting unresectable, bevacizumab significantly improved OS in the CPB group (not reached vs.18 months, p = 0.015), although PFS remained similar (CPB: 6 months, CP: 7 months, p = 0.741). While adding bevacizumab to NACT does not seem to increase the dIDS rate, it significantly extends OS in unresectable patients. Its use may be a valuable option in selected cases after eIDS' failure.

Risk reducing surgery with peritoneal staging in BRCA1-2 mutation carriers. A prospective study

International guidelines recommend risk-reducing salpingo-oophorectomy (RRSO) in BRCA1-2 mutations carriers to decrease ovarian cancer occurrence. In this prospective study, we describe the incidence of occult malignancies and the surgical outcomes in asymptomatic BRCA mutation carriers submitted to RRSO. Data on BRCA1-2 carriers undergoing RRSO with peritoneal washing and peritoneal/omental biopsies (PeS), between January 2019 until March 2021, were prospectively collected. A total of 132 patients were enrolled: 74 BRCA1 and 58 BRCA2 mutation carriers. 31.1% women underwent RRSO and PeS (16.2% of BRCA1 and 50% of BRCA2 carriers), while 68.9% patients were submitted also to concomitant hysterectomy. Almost all the procedures (99.2%) were performed by minimally invasive surgery. Postoperative complications occurred in twelve patients (9.1%): 10 in the concomitant hysterectomy group and two complications in the RRSO group. At the final pathological examination, 6 (4.5%) occult carcinomas were diagnosed: 3 fallopian tube carcinomas, one ovarian carcinoma and two serous tubal intraepithelial carcinomas (STICs), with negative PeS. Median age of occult carcinomas patients at RRSO was 54 (range: 48-79) years. The mean follow up was 20 (range: 7-34) months. During the follow up, no primary peritoneal cancer has been diagnosed. Occult pathologic findings in RRSO occurred in 4.5% (3% invasive carcinomas, STIC 1.5%) among our patients. The routine use of peritoneal biopsies does not improve the detection of occult malignancies. Our data confirm the importance of timely performing RRSO in BRCA1-2 carriers.

Real-world outcomes of PARP inhibitor maintenance in advanced ovarian cancer: a focus on disease patterns and treatment modalities at recurrence

The utilization of poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) as a first-line maintenance therapy for advanced ovarian cancer has increased significantly, with ∼80% of patients potentially eligible. This expansion has led to a rise in the population experiencing platinum-sensitive recurrence, yet data on first recurrence during PARPi are limited. This real-world study from a high-volume referral center aims to elucidate recurrence rates, disease distribution, and treatment modalities at the time of progression in PARPi-treated patients. We analyzed our prospectively maintained database to identify patients receiving first-line PARPi maintenance from January 2019 to December 2022 at our institution. A total of 373 cases were identified, 51.5% of which had a BRCA mutation. With a median follow-up of 38 months, 44.8% of patients experienced recurrence, with 90.3% having a platinum-free interval exceeding 6 months. Recurrences were oligometastatic in 44.9% of cases, with BRCA mutations strongly predicting this pattern (hazard ratio 3.014, confidence interval 1.486-6.113, P = 0.002). The median progression-free survival was 39 months, significantly longer for BRCA-mutated and homologous recombination deficiency-positive patients. Over one-third of platinum-sensitive recurrent patients were candidates for local treatments, and PARPi administration was prolonged in 53.7%. Despite the notable survival improvement, a significant proportion of the population will experience a platinum-sensitive recurrence on PARPi, for which local treatments are often a viable option. Our study highlights the need for further research to determine whether the ablation of oligometastatic sites has a significant impact on post-recurrence survival and to identify if there are patient categories that would benefit from personalized follow-up due to their susceptibility to oligometastatic recurrences and local treatments.