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Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings.

ABSTRACT: : Level I evidence exists for use of adjuvant chemotherapy in stage IIIC endometrial cancer (positive lymph nodes), although results of randomized trials have varied. Chemotherapy is also often recommended for high-risk subsets of stage I disease, such as serous carcinomas, although prospective trial data to validate this practice are lacking. Carboplatin plus paclitaxel is the current standard regimen, based on extrapolation of data from the metastatic setting. Several clinical trials have compared adjuvant pelvic radiotherapy alone to a combination of radiotherapy and chemotherapy with mixed results. One of the largest of these trials, Postoperative Radiation Therapy in Endometrial Carcinoma 3 (PORTEC-3), has completed accrual and is awaiting data maturation. Metastatic disease is not curable. For tumors of low-grade endometrioid histology with a prolonged time to recurrence, endocrine therapy with a progestin-based regimen is appropriate. Chemotherapy will be used in most other cases, and the standard first-line regimen is carboplatin and paclitaxel. Few chemotherapy agents have been shown to produce meaningful response rates in the second-line setting. Molecularly targeted therapies such as mTOR inhibitors and antiangiogenic agents including bevacizumab have been studied but their role in the armamentarium remains uncertain.Following surgical resection and staging for endometrial cancer, adjuvant chemotherapy with carboplatin and paclitaxel can be administered to patients with a high risk for recurrence. This includes patients with stage IIIC disease with positive lymph nodes, and high-risk subsets of stage I disease such as serous carcinomas. In the metastatic setting, endocrine therapy can be considered, particularly for patients with lower-grade disease and a prolonged time to recurrence. Combined therapy with carboplatin and paclitaxel is the standard of care used for front-line chemotherapy. Antiangiogenic agents are clearly active, but how they should be integrated into treatment is not yet determined. Immunotherapy is a promising direction for patients with mismatch repair-deficient or polymerase ?-mutated tumors.

SUBMITTER: Bestvina CM

PROVIDER: S-EPMC5061541 | biostudies-other | 2016 Oct

REPOSITORIES: biostudies-other

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Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings.

Bestvina Christine M CM Fleming Gini F GF

The oncologist 20160713 10

: Level I evidence exists for use of adjuvant chemotherapy in stage IIIC endometrial cancer (positive lymph nodes), although results of randomized trials have varied. Chemotherapy is also often recommended for high-risk subsets of stage I disease, such as serous carcinomas, although prospective trial data to validate this practice are lacking. Carboplatin plus paclitaxel is the current standard regimen, based on extrapolation of data from the metastatic setting. Several clinical trials have comp ...[more]

PMID: 27412393

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Project description:Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer.To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer.We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment.We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse.Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly favouring the addition of postoperative platinum based chemotherapy. The HR for progression-free survival is 0.75 (0.64 to 0.89). This means that chemotherapy reduces the risk of being dead at any censorship by a quarter. Chemotherapy reduces the risk of developing the first recurrence outside the pelvis (RR = 0.79 (0.68 to 0.92), 5% absolute risk reduction; NNT = 20). The analysis of pelvic recurrence rates is underpowered but the trend suggests that chemotherapy may be less effective than radiotherapy in a direct comparison (RR = 1.28 (0.97 to 1.68)) but it may have added value when used with radiotherapy (RR = 0.48 (0.20 to 1.18)).Postoperative platinum based chemotherapy is associated with a small benefit in progression-free survival and overall survival irrespective of radiotherapy treatment. It reduces the risk of developing a metastasis, could be an alternative to radiotherapy and has added value when used with radiotherapy.

Project description:BackgroundStandard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear.MethodsIn this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort.ResultsIn the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy.ConclusionsIn patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).

Project description:Highlights • Among subjects who underwent hysterectomy for endometrial cancer, 19% received adjuvant chemotherapy.• Platinum and taxane based chemotherapy is the most commonly used adjuvant chemotherapy.• Platinum and taxane combination therapy was used in 48% of patients at first recurrence. Objective The objective of this study was to describe patterns of utilization of cytotoxic, hormonal, and immunotherapy in patients with endometrial cancer in the adjuvant setting and at the time of first recurrence. Methods We identified patients in the IBM MarketScan database with endometrial cancer who underwent hysterectomy from 2011 to 2019. The use of clinically relevant therapeutic agents and combination regimens was determined in the adjuvant setting and at the time of first recurrence. Results A total of 22,632 patients were identified. Of these, 7,147 patients (31.6%) received adjuvant radiation and 4,381 (19.4%) received adjuvant chemotherapy following surgery. Of those who received adjuvant chemotherapy, the most commonly utilized agents were carboplatin (90.3%), paclitaxel (85.8%), cisplatin (9.4%), docetaxel (9.3%), gemcitabine (3.8%), and doxorubicin (2.0%), while bevacizumab was utilized in 1.5% of patients. A combination of platinum and a taxane were utilized as adjuvant therapy in 88.8% of women. Of the cohort, 1,825 patients (8.1%) recurred, of whom 1,017 patients had already received adjuvant chemotherapy. The median time from hysterectomy to initiation of chemotherapy for recurrence was 13.3 months (IQR: 7.6–23.1 months). Overall, platinum and taxane combination therapy was used in 788 (46.8%) of patients with recurrent disease, platinum alone or with other drugs in 194 (11.5%), taxanes alone or with other drugs in 145 (8.6%), and non-platinum and non-taxane based therapy in 31.3%. Conclusions Among patients with endometrial cancer who underwent hysterectomy, platinum-taxane combination chemotherapy was used in almost 90% of patients who received adjuvant chemotherapy while nearly 70% of patients who recurred were treated with platinum or taxane based therapy at first recurrence.

Project description:ObjectiveWhile primary cytoreductive surgery (PCS) is considered the standard of care for women who present with stage IV endometrial cancer, neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) has emerged as an alternative treatment strategy. We summarized the literature and compared outcomes of PCS compared to NACT and ICS.MethodsWe conducted a systematic search on PubMed, Embase, Web of Science, and Scopus for articles published from January 1, 1990 to December 31, 2020. Key search terms included multiple descriptors of advanced disease status in combination with "endometrial cancer" and "neoadjuvant chemotherapy". Our review included studies that examined survival and surgical outcomes of patients with stage III or IV endometrial cancer treated with neoadjuvant chemotherapy followed by interval cytoreductive surgery versus those who received primary cytoreductive surgery. We excluded studies examining only patients with leiomyosarcomas, carcinosarcomas, and stromal sarcomas due to the biologic heterogeneity of these malignancies.ResultsThe nine included studies encompassed 5,844 patients, of which 1,317 (22.5%) received NACT and 4,527 received PCS (77.5%). With the exception of a single study, all were retrospective observational studies or case series. Use of NACT in patients with stage IV EC increased from 16.0% in 2010 to 23.9% in 2015. Five studies analyzed median overall survival and all but one reported no significant difference between NACT + ICS vs. PCS. Optimal cytoreduction (<1 cm of residual disease) rates were similar across both treatment groups in three separate analyses, however pooled data suggest improved rates of optimal cytoreduction for NACT + ICS vs. PCS patients (81.9% vs. 51.5% respectively). Patients receiving NACT experienced significantly shorter hospital admissions and lower operative times compared to PCS counterparts.ConclusionsNACT followed by ICS reduces perioperative morbidity while offering similar overall survival.

Dataset Information

Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings.

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Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings.

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