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Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1–2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients’ conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy.

Introduction The role of cytoreductive surgery in the poly-ADP ribose polymerase inhibitors era is not fully investigated. We evaluated the impact of surgery performed prior to platinum-based chemotherapy followed by olaparib maintenance in platinum-sensitive BRCA-mutated recurrent ovarian cancer. Methods This retrospective study included platinum-sensitive recurrent ovarian cancer BRCA-mutated patients from 13 Multicenter Italian Trials in Ovarian cancer and gynecological malignancies centers treated between September 2015 and May 2019. The primary outcomes were progression-free survival and overall survival. Data on post-progression treatment was also assessed. Results Among 209 patients, 72 patients (34.5%) underwent cytoreductive surgery followed by platinum-based chemotherapy and olaparib maintenance, while 137 patients (65.5%) underwent chemotherapy treatment alone. After a median follow-up of 37.3 months (95% CI: 33.4 to 40.8), median progression-free survival in the surgery group was not reached, compared with 11 months in patients receiving chemotherapy alone (P<0.001). Median overall survival was nearly double in patients undergoing surgery before chemotherapy (55 vs 28 months, P<0.001). Post-progression therapy was assessed in 127 patients: response rate to chemotherapy was 29.2%, 8.8%, and 9.0% in patients with platinum-free interval >12 months, between 6 and 12 months, and <6 months, respectively. Conclusion Cytoreductive surgery performed before platinum therapy and olaparib maintenance was associated with longer progression-free survival and overall survival in BRCA-mutated platinum-sensitive relapsed ovarian cancer patients. In accordance with our preliminary results, the response rate to chemotherapy given after progression during olaparib was associated with platinum-free interval.

Objectives: Olaparib is approved as maintenance therapy in patients with BRCA mutated platinum sensitive (PS) recurrent ovarian cancer (OC) after response to last platinum based therapy. Few data are available regarding the use out of the registration trials and on response to further treatments after progression. Materials ad methods: In this non interventional, retrospective study, patients treated with olaparib in 13 centers, according to the label, have been collected and analyzed. Primary objectives of the study are to describe effectiveness and safety of olaparib in a real world setting with a focus on post progression treatments and response. Results: 234 patients were analyzed. All patients were BRCA mutated and most of them had germline mutations. Around 50% of the patients received olaparib after 3 or more lines of platinum based chemotherapy achieving a radiologic complete (CR) or partial response. 12.4% patients with stable disease were also included. Median PFS was 14.7 months (95% CI:12.6–18), with statistically longer PFS in patients with normal serum Ca125 at baseline, a CR after last platinum based therapy and that received olaparib after second platinum based therapy. Median OS was not reached. Most frequent G3-G4 toxicity was anaemia (6%) with dose discontinuation and dose reduction in 11 (4.7%) and 49 (20.9%) of cases, respectively. Among 66 patients receiving further treatment after olaparib progression and evaluable for response, ORR was 22.2, 11.1% and 9.5% in patients with Platinum Free interval (PFI) of more than 12 months, between 6 and 12 months and less than 6 months, respectively. Conclusions: Olaparib is effective and safe in real world setting. Data on post-progression treatments seem to suggest cross resistance with chemotherapy and need to be confirmed in larger studies because of the potential importance in clinical practice decisions.

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1–2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients’ conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy.

The aim of this multicenter, retrospective study was to evaluate the efficacy and the safety of single agent Trabectedin (ET-743, Yondelis) in very heavily treated, relapsed ovarian cancer (ROC) patients.

Objective: To identify differences in the management and outcome of patients with central nervous system metastases from epithelial ovarian cancer. Methods: The clinical and pathologic characteristics, treatment, and outcome of 23 patients with brain metastases from epithelial ovarian cancer who were treated during 1982-1994 were compared with those of 20 patients treated during 1995-2010 at the same center. Results: No differences were found in terms of primary tumor characteristics, time interval from ovarian cancer diagnosis to brain involvement diagnosis, sites of metastasis, and presence of extracranial disease. The main difference between the 2 groups was the therapeutic approach. During 1982-1994, most patients received radiotherapy only, whereas most patients during 1995-2010 underwent surgical resection followed by radiotherapy and/or chemotherapy. The duration of survival during 1982-1994 was 5 months, which was significantly shorter than the duration of survival (18 months) during 1995-2010. Conclusion: An aggressive multimodal treatment approach might prolong the survival of patients with brain involvement from ovarian cancer.