ABSTRACT
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.
Subject(s)
Carcinoma, Ovarian Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Propensity Score , Adult , Aged , Carcinoma, Ovarian Epithelial/mortality , Chemotherapy, Adjuvant , Female , Humans , Middle Aged , Neoadjuvant Therapy , Ovarian Neoplasms/mortalityABSTRACT
OBJECTIVE: The aim of this study was to investigate the correlation between BRCA mutational status and response to bevacizumab in a large advanced ovarian cancer (AOC) series. METHODS: This is a multicenter, retrospective case-control study including upfront AOC treated between January 2015 and June 2019. The main inclusion criteria were: having received three weekly carboplatin-paclitaxel as first-line treatment, with or without Bevacizumab maintenance, knowledge of the BRCA mutational status. RESULTS: Overall, 441 patients were included; 183 (41.5%) patients received bevacizumab (Cases), and 258 (58.5%) did not receive it (Controls). The BRCA mutated patients (BRCAmut) were 58 (39%) in the Cases group and 90 (34.9%) in the Controls group (p = .77). Patients who received bevacizumab had a significant 4-months increase in median progression free survival (mPFS: 21 vs. 17 months, p = .033). Concerning BRCAmut patients, no differences were shown between those who received bevacizumab or not in terms of mPFS (24 vs. 22 months, p = .3). Conversely, in BRCA wild-type (BRCAwt) population bevacizumab administration significantly prolonged mPFS (20 vs 15 months, p = .019). At multivariate analysis, independent factors of prolonged PFS were BRCA status (OR = 0.60), having received PDS (OR = 0.69), and complete cytoreduction (OR = 0.50), but not the bevacizumab administration (OR = 0.83, p = .22). CONCLUSIONS: No evidence of oncological benefit in terms of PFS and OS related to bevacizumab maintenance therapy was found in BRCAmut patients. Differently, BRCAwt patients seem to benefit from antiangiogenic treatment in terms of mPFS.
Subject(s)
Angiogenesis Inhibitors/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab/administration & dosage , Cytoreduction Surgical Procedures , Ovarian Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Angiogenesis Inhibitors/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Bevacizumab/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Case-Control Studies , Chemotherapy, Adjuvant/adverse effects , Chemotherapy, Adjuvant/methods , Disease Progression , Female , Humans , Maintenance Chemotherapy/adverse effects , Maintenance Chemotherapy/methods , Middle Aged , Mutation , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Ovary/drug effects , Ovary/pathology , Ovary/surgery , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Progression-Free Survival , Retrospective StudiesABSTRACT
For many decades, ovarian cancer (OC) has been one of the most common gynecological cancer. Despite advances in OC diagnosis and treatment, the risk of recurrence is ever present and approximately 85% of patients will experience relapse. Recurrent OC after first-line therapy is almost always incurable. Multiple novel therapies, including tyrosine-kinases inhibitors (TKI), have shown promising results, but their role needs to be clarified. In this review we describe the rationale and the clinical evidence regarding the use of TKI for the treatment of recurrent platinum-resistant OC patients.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma/drug therapy , Molecular Targeted Therapy , Neoplasm Proteins/antagonists & inhibitors , Organoplatinum Compounds/pharmacology , Ovarian Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacology , Carcinoma/enzymology , Carcinoma/secondary , Clinical Trials, Phase II as Topic , Drug Resistance, Neoplasm/drug effects , Female , Humans , Multicenter Studies as Topic , Organoplatinum Compounds/therapeutic use , Ovarian Neoplasms/enzymology , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/pharmacology , Randomized Controlled Trials as Topic , Recurrence , Treatment OutcomeABSTRACT
BACKGROUND: The purpose of this study was to observe the role of secondary cytoreductive surgery in platinum-resistant recurrent ovarian cancer (OC) patients. METHODS: We collected data of patients affected by recurrent OC treated between 1995 and 2013. Inclusion criteria were: invasive epithelial OC histologically documented, cytoreductive surgery and platinum-based chemotherapy at first-line treatment with evidence of complete response to treatment, disease-free interval <6 months, and no concomitant neoplasia. Patients considered susceptible of cytoreductive surgery (group A) were compared with a historical series of patients with similar characteristics but not eligible for surgery (group B). RESULTS: Of 122 platinum-resistant patients, 18 met the inclusion criteria for the study and were enrolled. They were compared with a historical series of 18 patients not surgically treated with analogous clinical and pathological features. The most frequent sites of relapse included pelvic and aortic lymph nodes (39 %), peritoneum (33 %), bowel (28 %), and pelvis (22 %). A low rate of intraoperative and postoperative complications was reported. No deaths were recorded. Overall survival was significantly longer in cytoreductive group when compared with the control group (P = 0.035). Median overall survival was 44 months. Estimated 5-year overall survival rates were 57 versus 23.5 % for groups A and B, respectively. CONCLUSIONS: Surgery could represent a useful adjunct to chemotherapy in the management of platinum-resistant recurrent OC patients, carefully selected, in highly selected centers. Larger prospective trials are needed to further confirm our experience.
