To evaluate the impact of two different intraperitoneal (IP) chemotherapy regimens on progression-free survival (PFS) among women with newly diagnosed advanced ovarian carcinoma.
Eligible patients ...were randomly assigned to six cycles of IV paclitaxel 80 mg/m
once per week with intravenous (IV) carboplatin area under the curve 6 (IV carboplatin) versus IV paclitaxel 80 mg/m
once per week with IP carboplatin area under the curve 6 (IP carboplatin) versus once every 3 weeks IV paclitaxel 135 mg/m
over 3 hours day 1, IP cisplatin 75 mg/m
day 2, and IP paclitaxel 60 mg/m
day 8 (IP cisplatin). All participants received bevacizumab 15 mg/kg IV every 3 weeks in cycles 2 to 22.
A total of 1,560 participants were enrolled and had 84.8 months of follow-up. The median PFS duration was 24.9 months in the IV carboplatin arm, 27.4 months in the IP carboplatin arm, and 26.2 months in the IP cisplatin arm. For the subgroup of 1,380 patients with stage II/III and residual disease of 1 cm or less, median PFS was 26.9 (IV-carboplatin), 28.7 (IP-carboplatin), and 27.8 months (IP cisplatin), respectively. Median PFS for patients with stage II/III and no residual disease was 35.9, 38.8, and 35.5 months, respectively. Median overall survival for all enrolled was 75.5, 78.9, and 72.9 months, respectively, and median overall survival for stage II/III with no gross residual disease was 98.8 months, 104.8 months, and not reached. Mean patient-reported Functional Assessment of Cancer Therapy neurotoxicity scores (Gynecologic Oncology Group) were similar for all arms, but the mean Trial Outcome Index of the Functional Assessment of Cancer Therapy-Ovary scores during chemotherapy were statistically worse in the IP cisplatin arm.
Compared with the IV carboplatin reference arm, the duration of PFS was not significantly increased with either IP regimen when combined with bevacizumab and was better tolerated than IP cisplatin.
•Treatment options are limited for recurrent ovarian carcinosarcoma (OCS).•A patient with HER2 1 + IHC and negative FISH amplification was treated with trastuzumab deruxtecan.•A durable partial ...response was achieved, suggesting a possible treatment option for OCS patients with HER2 expression.
To identify factors predictive of poor prognosis in a similarly treated population of women with stage IV epithelial ovarian cancer (EOC).
A retrospective review of 360 patients with International ...Federation of Gynecology and Obstetrics stage IV EOC who underwent primary surgery followed by six cycles of intravenous platinum/paclitaxel was performed. A proportional hazards model was used to assess the association of potential prognostic factors with progression-free survival (PFS) and overall survival (OS).
The median PFS and OS for this group of stage IV ovarian cancer patients was 12 and 29 months, respectively. Multivariate regression analysis revealed that histology, malignant pleural effusion, intraparenchymal liver metastasis, and residual tumor size were significant prognostic variables. Whereas patients with microscopic residual disease had the best outcome, patients with 0.1 to 1.0 cm residual disease and patients with 1.1 to 5.0 cm residual disease had similar PFS and OS. Patients with a residual size more than 5 cm had a diminished PFS and OS when compared with all other groups. Median OS for microscopic, 0.1 to 5.0 cm, and more than 5.0 cm residual disease was 64, 30, and 19 months, respectively.
Patients with more than 5 cm residual disease have the shortest PFS and OS, whereas patients with 0.1 to 1.0 and 1.1 to 5.0 cm have similar outcome. These findings suggest that ultraradical cytoreductive procedures might be targeted for selected patients in whom microscopic residual disease is achievable. Patients with less than 5.0 cm of disease initially and significant disease and/or comorbidities precluding microscopic cytoreduction may be considered for alternative therapeutic options other than primary cytoreduction.
To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic ...recurrence.
We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration.
Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated.
Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes.
Previous studies have shown that this vaccine can cause significant regression of cervical intraepithelial neoplasia 3.2 The concept of using a combination of a therapeutic antigen-specific vaccine ...against HPV (ISA 101) and an immune checkpoint inhibitor (nivolumab) previously showed a 33% objective response rate in patients with HPV-positive head and neck cancer.3 Vaccination with GDX-188E combined with pembrolizumab was well tolerated and resulted in an overall response rate of 42% (95% CI 23–63), which was higher than the response rate of 14·6% with pembrolizumab alone in PD-L1 positive cervical cancer.4 As ten (91%) of 11 responders were PD-L1-positive, the overall response rate among these patients was 50% (95% CI 27–73). An alternative approach could be to treat patients with small tumour burden in first-line settings, such as those in complete clinical remission. 30–70% of patients in complete clinical remission have persistent disease.6 These patients are destined to have disease recurrence and are most likely to benefit from active maintenance therapy, where the immune system is less compromised compared with a later recurrent tumour setting. ...previous immunotherapies against CA-125 and NY-ESO-1 antigens at the time of complete response after primary chemotherapy did not show clear clinical benefit despite producing serological responses.7,8 In a large randomised trial of abagovomab in 888 patients with epithelial ovarian cancer, no survival benefit was seen.7 Rodney Rocconi and colleagues9 report an alternative vaccine strategy.
Introduction: Endometrial cancer is the most common gynecologic malignancy in the developed world, and its incidence is increasing. Mortality from this cancer has not improved in recent decades and ...is primarily driven by high-grade carcinomas that are more likely to present at an advanced stage and ultimately are more likely to recur. The prognosis for recurrent endometrial cancer is poor, especially for the 50% of these women that present with extrapelvic disease recurrence. As a standard of care, recurrent disease has been treated with platinum-based chemotherapy; however, new therapies are emerging as we identify drivers of proliferation and metastasis at the cellular and molecular levels.
Areas Covered: We review currently available data for the management of recurrent endometrial cancer, with a focus on systemic treatment of recurrent disease. We discuss the available evidence for first-line, second-line, and subsequent systemic therapy and discuss emerging therapeutic targets including their biologic plausibility and early clinical data.
Expert Commentary: Endometrial cancer, though prevalent, remains underfunded and understudied. Recurrent and metastatic disease remains difficult to treat, and prospective randomized data are limited. Our ability to reduce mortality due to this cancer is dependent on identifying new and effective therapeutic strategies for recurrent disease.
Role of Surgery in Ovarian Carcinoma Fader, Amanda Nickles; Rose, Peter G
Journal of clinical oncology,
07/2007, Letnik:
25, Številka:
20
Journal Article
Recenzirano
Surgery plays a critical role in the optimal management of all stages of ovarian carcinoma. In apparent early-stage ovarian cancer, a comprehensive surgical evaluation allows stratification of ...patients into low- and high-risk categories. Low-risk patients may be candidates for fertility-sparing surgery and can safely avoid chemotherapy and be observed. Treatment of patients with high-risk early- or advanced-stage ovarian cancer usually requires a combined modality approach. Although it is well known that epithelial ovarian cancer is moderately chemosensitive, what distinguishes it most from other metastatic solid tumors is that surgical cytoreduction of tumor volume is highly correlated with prolongation of patient survival. Procedures such as radical pelvic surgery, bowel resection, and aggressive upper abdominal surgery are commonly required to achieve optimal cytoreduction. Women who develop recurrent disease may be eligible for a secondary cytoreductive surgery or may require a surgical intervention to palliate disease-related symptoms. For women at high risk of ovarian cancer, prophylactic bilateral salpingo-oophorectomy significantly reduces the incidence of this disease. The purpose of this article is to provide a comprehensive review of the surgical management of ovarian carcinoma. The roles of primary, interval, and secondary cytoreductive surgeries; second-look procedures; and palliative surgery are reviewed. The indications for fertility-sparing and minimally invasive surgery as well as the current guidelines for prophylactic surgery in high-risk mutation carriers are also discussed.
Conflicting results on prognostic factors for advanced epithelial ovarian cancer (EOC) have been reported because of small sample size and heterogeneity of study population. The purpose of this study ...was to identify factors predictive of poor prognosis in a similarly treated population of women with advanced EOC.
A retrospective review of demographic, pathologic, treatment, and outcome data from 1,895 patients with International Federation of Gynecology and Obstetrics stage III EOC who had undergone primary surgery followed by six cycles of intravenous platinum/paclitaxel was conducted. A proportional hazards model was used to assess the association of prognostic factors with progression-free survival (PFS) and overall survival (OS).
Increasing age was associated with increased risks for disease progression (HR = 1.06; 95% CI, 1.02 to 1.11 for an increase every 10 years) and death (HR = 1.12; 95% CI, 1.06 to 1.18). Mucinous or clear-cell histology was associated with a worse PFS and OS compared with serous carcinomas. Patients with performance status (PS) 1 or 2 were at an increased risk for recurrence compared with PS 0 (HR = 1.12; 95% CI, 1.01 to 1.24). Compared with patients with microscopic residual disease, patients with 0.1 to 1.0 cm and > 1.0 cm residual disease had an increased risk of recurrence (HR = 1.96; 95% CI, 1.70 to 2.26; and HR = 2.36; 95% CI, 2.04 to 2.73, respectively) and death (HR = 2.11; 95% CI, 1.78 to 2.49; P < .001; and HR = 2.47; 95% CI, 2.09 to 2.92, respectively).
Age, PS, tumor histology, and residual tumor volume were independent predictors of prognosis in patients with stage III EOC. These data can be used to identify patients with poor prognosis and to design future tailored randomized clinical trials.
In view of the high risk of recurrent disease in stage III and IV ovarian cancer following primary first-line chemotherapy, a variety of maintenance and consolidation treatment strategies have been ...developed. These have included: radiation, intravenous or intraperitoneal chemotherapy, targeted therapies, and immunotherapy. Popular at this time is the use of Poly-adenosine ribose polymerase (PARP) inhibitors and bevacizumab as maintenance therapy. What effect these maintenance or consolidation therapies have on subsequent response to therapy, specifically platinum-based chemotherapy, is only beginning to be studied. In this manuscript, we review the impact of PARP inhibitors and bevacizumab as well as radiation and maintenance chemotherapy on subsequent response to treatment. Prior use of bevacizumab does not appear to adversely affect subsequent response to platinum-based chemotherapy or platinum-based chemotherapy with bevacizumab. Prior therapy with PARP inhibitors induces platinum resistance to subsequent platinum-based therapy and negates classic predictors of response such as platinum-free interval and breast cancer susceptibility gene (BRCA) mutational status.
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