Our objective was to assess the safety and efficacy of olaparib in maintenance therapy of BRCA 1-2 mutated, platinum-sensitive, recurrent ovarian carcinoma after the partial or complete response to the second or further lines platinum-based chemotherapy in a real-world setting. We performed a multicenter, real-world observational population-based cohort study on the whole population of Croatian patients initiated to olaparib maintenance therapy between 2016 and 2020. The primary endpoints were progression-free survival and the discontinuation of treatment because of adverse events. We enrolled the total population of 69 patients with the median (interquartile range; IQR) age of 53 (48–59), 56 (81%) of them with BRCA1 mutation. The median (IQR) follow-up was 16 (9–25) months. Treatment had to be discontinued because of toxicity in 2 (3%) and temporarily interrupted in 14 (20%), while dose was reduced because of toxicity in 18 (26%) of patients. Toxicity of any grade was observed in 61 (88%) patients and toxicity of grade 3 or 4 in 12 (17%). Median progression-free survival was 21 (95% CI 16-not calculable) months from the introduction of olaparib, and the median overall survival was not reached. Our study confirmed efficacy and safety of olaparib as the maintenance therapy of BRCA 1-2 mutated, platinum-sensitive, recurrent ovarian carcinoma. We observed the real-world efficacy and safety comparable to those observed in the randomized controlled trials. We found the interesting observation of better efficacy of 300 mg tablets, compared to 400 mg capsules, an issue that should be addressed on much larger real-world populations.
Comprehensive genomic profiling (CGP) is gradually becoming an inevitable part of the everyday oncology clinical practice. The interpretation and optimal implementation of the results is one of the hot topics of modern-day oncology. According to the recent findings, uterine cancer harbors a high level of gene alterations but is still insufficiently explored. The primary goal of this project was to assess the proportion of patients with targetable mutations. Also, the aim was to define and emphasize potential opportunities as well as the problems we have faced in the first year of testing on the national level. We performed a multicentric, retrospective, nested cross-sectional analysis on the total population of Croatian patients with advanced/metastatic uterine cancer where the tumor CGP was performed during 2020. CGP of the tumor tissue of 32 patients revealed clinically relevant genomic alterations (CRGA) in 27 patients (84%) with a median of 3 (IQR 1-4) CRGA per patient. The most common CRGAs were those of phosphatide-inositol-3 kinases (PIK3) in 22 patients (69%), with 13/22 (59%) of those patients harboring PIK3CA mutation. The next most common CGRAs were ARID1A and PTEN mutations in 13 (41%) and 11 (34%) patients, respectively. Microsatellite status was determined as stable in 21 patients (66%) and highly unstable in 10 patients (31%). A high tumor mutational burden (≥10Muts/Mb) was reported in 12 patients (38%). CGP analysis reported some kind of targeted therapy for 28 patients (88%). CGP determined clinically relevant genomic alterations in the significant majority of patients with metastatic uterine cancer, defining it as a rich ground for further positioning and development of precision oncology.
Background. Although today it is almost preventable, cervical cancer still represents a significant cancer burden, especially in some developing parts of the world. Since the introduction of bevacizumab in the first-line treatment of metastatic disease, improvements of the outcomes were noted. However, results from randomized controlled trials are often hard to recreate in the real-world setting. Objective. To assess the real-world efficacy and safety of bevacizumab as a first-line treatment of advanced cervical cancer. Methods. We conducted a retrospective cohort study on the total population of Croatian patients diagnosed with metastatic cervical cancer from 2016 to 2019 who were treated with bevacizumab in combination with cisplatin and paclitaxel (TCB) in the first line. The comparison group was the consecutive sample of patients treated with chemotherapy alone. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, incidence of adverse events, and the proportion of treatment discontinuation. Results. We enrolled 67 patients treated with TCB and a control group of 62 patients treated with chemotherapy alone. The TCB cohort had significantly longer unadjusted OS with a median of 27.0 (95% CI 18.5; not calculable) months, compared to 15.5 (10.7; 30.1) months in the chemotherapy-alone cohort. Adjusted OS was not significantly different. PFS was significantly longer for the TCB cohort, with a median of 10.6 (95% CI 8.5; 15.4) months, than for the chemotherapy-alone cohort, with a median of 5.4 (95% CI 3.9; 9.1) months, even after adjustment for baseline covariates (HRadjusted = 0.60; 95% CI 0.39; 0.94; p = 0.027 ; false discovery rate <5%). Conclusions. In a real-world setting, TCB as a first-line treatment of metastatic cervical cancer was associated with longer PFS, better objective disease control rate, and acceptable toxicity profile in comparison to chemotherapy alone. These results may indicate its utility and potential applicability in other parts of the developing world.
Introduction: Bevacizumab is a recombinant humanized anti-VEGF monoclonal antibody. It is an effective treatment for epithelial ovarian cancer, both in primary and recurrent disease. The incidence of ovarian cancer increases with advancing age. Despite the high prevalence of the ovarian cancer in elderly, the management of these patients is often less aggressive than in younger patients. In Croatia, from February 2017, we have opportunity to treat patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer with bevacizumab in the first-line and second-line settings. Our aim was to investigate the safety of bevacizumab administration in patients older than 65 years. Methods:We have retrospectively analyzed the archive data of 65 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer who started treatment with bevacizumab in primary advanced and in first relapse setting at the Department of Gynecologic Oncology in the University Hospital Centre Zagreb in the period from January 2017 to December 2018. Patients were divided in two categories according to age: group 1 (≤65 years) and group 2 (>65 years).Results: Our analysis included 65 patients:47 (72.3%) patients in group 1 compared with 18 (27.7%) in group 2. Bevacizumab was administered to 39 (60%) patients as first-line treatment and to 26 (40%) patients as second-line treatment. The median age was 70 years (range 66-76 years) in group 2 and 55 years (range 35-65 years) in group 1. ECOG status 0 had 44.7% of patients in group 1 compared with only 22% in group 2. At the time of diagnosis, elderly patients had presented with at least one comorbidity in 94.4% of the cases, compared with 42.6% in group 1. The median number of cycles of bevacizumab was 9 in elderly patients and 17 cycles in group 1. Among those patients receiving bevacizumab in the first-line setting, median progression free interval (PFI) was 12 months in younger patients versus 7 months in elderly patients. Similarly, among those receiving bevacizumab in the second-line setting PFI was 9 months in younger patients versus 1 months in elderly patients. The occurrence of non-hematological adverse events did not increase in elderly patients; 51.1% of patients in group 1 reported some of non-hematological adverse events versus only 27.8% in elderly patients. Conclusion:Our experience in treating patients with bevacizumab shows good results with acceptable toxicity and our findings suggest that its use in the elderly population should be considered as safe and manageable.
Epithelial ovarian cancer is the seventh most common cancer among women and the leading cause of gynecological cancer related deaths in Croatia. Approximately 70% of patients are diagnosed at an advanced stage of the disease (FIGO III and IV). The usual approach to treatment involves complete surgical cytoreduction (R0), followed by combined platinumbased chemotherapy. Bevacizumab is recommended to add to paclitaxel/carboplatin chemotherapy in patients diagnosed at FIGO IIIB and IIIC stage with residual disease after surgery and all patients FIGO IV stage of disease, which can extend the time to progression of the disease in these patients. In this retrospective study, we analyzed the medical data of 98 patients with newly diagnosed advanced FIGO IIIB-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer treated at the Department of Gynecology and Obstetrics in the University Hospital Centre Zagreb in the period from January 2017 to December 2018. We have analyzed the following data: age, ECOG status, FIGO stage of disease, principle of surgery, pathohistological type of the tumor, number and type of adjuvant chemotherapy, application of bevacizumab, number of bevacizumab cycles, side effects related to bevacizumab therapy. Data from 98 patients were obtained. The median age was 60 years. The most patients were ECOG status 0-1 (78 %). According to the pathohistological findings, 89 % of patients had serous carcinoma, 5% endometrioid carcinoma, 3% mucinous carcinoma, 1% clear cell carcinoma, 1% borderline tumors and 1% poorly differentiated epithelial carcinoma. Most of the patients (68.5%) were underwent to primary cytoreduction, 12% "interval debulking" operation, whereas biopsy was performed in only 19.5% patients. HIPEC during surgery had 6% of patients. Resection without residual disease was achieved in only 25.5% of patients underwent surgery, while in others were reported macroscopic residual disease after surgery. 87% of patients were treated with chemotherapy with paclitaxel and carboplatin in three weeks schedule. 38 patients received antiangiogenetic drug bevacizumab. After exclusion of patients with a poor general condition (ECOG 2-4) and patients with FIGO stage IIIB and IIIC without residual disease after surgery, the percentage of patients receiving bevacizumab was 56% in 2017 and 75% in 2018. The average number of received cycles was 13 (range 1-22), and 8 patients continued the therapy in May 2019. Sixty-eight percent of the patients which received bevacizumab did not have any side effects associated with the bevacizumab therapy. The most common side effects associated with the bevacizumab were hypertension, development of deep vein thrombosis, ileus and proteinuria. In Croatia, since February 2017, we have the possibility of using bevacizumab for the treatment of newly diagnosed ovarian cancer patients stage IV or incompletely resected patients stages III B and III C. Our results are in concordance with the literature data and show that we can safely add bevacizumab to the first lin...
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