Optimizing the number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma: A propensity-score matching analysis.

OBJECTIVE: Neoadjuvant chemotherapy and interval debulking surgery are now widely offered in ovarian cancer patients unsuitable for surgery; the number of preoperative NACT cycles to be given is still an issue. Our aim was to compare survival outcomes of patients with advanced ovarian cancer treated with ≤4 or more NACT cycles. METHODS: A cohort of AEOC patients with stage III-IV epithelial OC who underwent NACT followed by IDS was identified. Patients were classified in group A (≤4 cycles) and group B (>4 cycles). Selection bias from the heterogeneity of demographic and clinical characteristics was avoided using propensity score matching (2:1 ratio). RESULTS: 140 (group A) and 70 (group B) patients were included. After the propensity score matching, there were no imbalances in baseline characteristics. BRCA status was associated to improved OS (HR = 0.41; 95%CI 0.18.0.92, p = 0.032) and residual tumor to decreased OS (HR = 1.93; 95%CI 1.08-3.46, p = 0.026). Statistically significant differences were not observed in OS (2-year OS 82.4% for group A versus 77.1% for group B, p = 0.109) and PFS (2-year PFS 29.7% for group A versus 20.0% for group A, p = 0.875). In group B, the administration of >4 cycles was related to an additional chance of achieving complete (12.9%) and partial (34.3%) responses compared to responses after 3-4 cycles. CONCLUSIONS: Receiving more than 4 cycles of NACT is no detrimental in terms of OS and PFS in advanced ovarian cancer. Response rates can increase following further cycles administration.

First-line carboplatin/nab-paclitaxel in advanced ovarian cancer patients, after hypersensitivity reaction to solvent-based taxanes: a single-institution experience.

One of the major challenges related to solvent-based taxanes administration in clinical practice is the high rate of hypersensitivity reactions (HSRs). Nab-paclitaxel is a solvent-free, albumin-bound, paclitaxel, which minimize the risk of HSR occurrence. In this single-institution, retrospective analysis, we evaluated stage IIIc-IV epithelial ovarian cancer (EOC) patients, treated with first-line carboplatin/nab-paclitaxel (± bevacizumab), after the occurrence of an HSR with solvent-based paclitaxel (and/or docetaxel). Between April 2012 and December 2018, ten patients (20.8%) received carboplatin/nab-paclitaxel (± bevacizumab) after the occurrence of an HSR to solvent-based taxanes. Among the evaluable patients, ORR was 100%. At median follow-up of 28.5 months, median PFS was 16.7 months, and median OS was 65.4 months, respectively. Median received dose intensity (DI) was 86% and 80% of the projected DI for nab-paclitaxel and carboplatin, respectively. There were no treatment-related grade 4 adverse events. Most relevant treatment-related grade 3 adverse events were: asthenia (10%), hypertransaminasemia (10%), neutropenia (20%), thrombocytopenia (20%), and anemia (10%). No HSR recurrence was observed. The high rate of HSR occurrence could limit first-line treatment options in clinical practice. Carboplatin/nab-paclitaxel association could represent a valid treatment option in this setting.

Secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer before olaparib maintenance: Still getting any benefit? A case-control study.

OBJECTIVE: The role of secondary cytoreductive surgery (SCS) in platinum-sensitive recurrent ovarian cancer (PSROC) is still controversial. We investigated the role of SCS in PSROC patients with BRCA1/2 mutation (BRCAmut) who received platinum-based chemotherapy followed by olaparib maintenance. METHODS: This is a case-control study. Patients with first PSROC admitted to our Gynecologic Oncology Unit between 2014 and 2018 were identified. Main eligibility criteria: positive BRCA1/2 germline or somatic mutation status and olaparib maintenance at primary recurrence after response to platinum-based chemotherapy. Cases were those who received SCS followed by medical treatment (SCS-CT-OLA, group 1), controls were those who received medical treatment alone (CT-OLA, group 2). RESULTS: Overall, 46 patients were identified; 23 (50%) BRCAmut women undergoing SCS followed by platinum-based chemotherapy and olaparib maintenance were matched with 23 (50%) BRCAmut women who only received medical treatment. Groups were well balanced: no statistical differences were found with regard of age, mutational status, treatment's approach at diagnosis, timing and patterns of disease presentation at recurrence. Median time to first subsequent therapy (TFST) was significantly longer in the SCS-CT-OLA than in the CT-OLA group (42 months vs 16 months; p = 0.05). Also, SCS-CT-OLA patients had the best post-recurrence survival (PRS), with a 3-year PRS of 79% in SCS-CT-OLA group versus 42% in CT-OLA group (p = 0.02). CONCLUSIONS: SCS increases TFST and PRS in PSROC patients with BRCAmut candidate for olaparib maintenance after platinum-based chemotherapy. Prospective studies are needed. In the era of personalized medicine, indication to SCS should be individualized.

Bioclinical parameters driving decision-making of subsequent lines of treatment in metastatic castration-resistant prostate cancer.

Different options are available as second-line treatment of metastatic castrate-resistant prostate cancer: cabazitaxel, abiraterone, and enzalutamide. Phase III studies evaluating cabazitaxel and the two hormonal agents have been shown to significantly prolong overall survival compared to mitoxantrone and placebo, respectively. Several studies have also demonstrated feasibility and activity of docetaxel rechallenge in case of a sufficient progression-free interval (3-6 months), good performance status, and previous acceptable safety profile, thus providing an additional treatment option in clinical practice. Clinical and biological parameters should be considered to tailor II line treatment. In clinical practice, we can primarily evaluate patients' fitness according to age, performance status, symptomatic disease, comorbidities, and expected safety profile of each drug. Different prognostic/predictive factors may be considered, such as presence of bone-limited or visceral metastases, length of androgen deprivation therapy (ADT) before chemotherapy, time to progression after docetaxel, Gleason score, PSA doubling time, and serum testosterone, even if their clinical relevance is still debated. This review will discuss current options of innovative drugs sequencing and selection according to bioclinical parameters.