A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer

Aghajanian, Carol; Filiaci, Virginia L.; Dizon, Don S.; Carlson, Jay W.; Powell, Matthew A.; Secord, Angeles Alvarez; Tewari, Krishnansu S.; Bender, David; O’Malley, David M.; Stuckey, Ashley; Gao, Jianjiong; Dao, Fanny; Soslow, Robert A.; Lankes, Heather A.; Moore, Kathleen N.; Levine, Douglas A.

doi:10.1016/j.ygyno.2018.05.018

Cited by 122 publications

(88 citation statements)

References 27 publications

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“…Bevacizumab yielded a response rate of 14% and a 6‐month PFS rate of 40% in women who received 1 to 2 prior cytotoxic regimens for endometrial cancer, which compares favorably with any other second‐line regimen . In the randomized phase 2 GOG 86P trial, the addition of bevacizumab to front‐line carboplatin and paclitaxel therapy did not improve PFS compared with historical controls, although it did increase OS (HR, 0.71 [95% CI, 0.55‐0.91]) . Conversely, a randomized phase 2 Italian trial (MITO END‐2) reported a significant increase in PFS from 8.7 to 13 months with the addition of bevacizumab to upfront carboplatin and paclitaxel chemotherapy, although these results have not been published in full .…”

Section: Future Directionsmentioning

confidence: 99%

“…Median survival for metastatic/recurrent endometrial cancer is short, on the order of 12 to 15 months for women with measurable disease (Table ) . For the majority of women, initial therapy for unresectable recurrent/metastatic disease will be chemotherapy with carboplatin and paclitaxel.…”

Section: Therapy For Recurrent or Metastatic Diseasementioning

confidence: 99%

“…However, no advantage was found from the addition of the mTOR inhibitor temsirolimus to standard carboplatin and paclitaxel chemotherapy, and multiple trials of single‐agent rapamycin‐analog mTOR inhibitors in advanced or recurrent disease have shown only modest activity (<25% response rates even in the setting of chemotherapy‐naive disease), and no association between activity and PTEN or PIK3CA alterations has been observed. One report noted significantly increased PFS and response rates in 3 patients whose tumors had AKT1 mutations …”

Section: Future Directionsmentioning

confidence: 99%

“…Median survival for metastatic/recurrent endometrial cancer is short, on the order of 12 to 15 months for women with measurable disease (Table 4). [112][113][114][115][116] For the majority of women, initial therapy for unresectable recurrent/metastatic disease will be chemotherapy with carboplatin and paclitaxel. For those with potentially endocrine-sensitive tumors, a trial of endocrine therapy, usually progestin-based, is appropriate.…”

Section: Therapy For Recurrent or Metastatic Diseasementioning

confidence: 99%

“…133 In the randomized phase 2 GOG 86P trial, the addition of bevacizumab to front-line carboplatin and paclitaxel therapy did not improve PFS compared with historical controls, although it did increase OS (HR, 0.71 [95% CI, 0.55-0.91]). 116 Conversely, a randomized phase 2 Italian trial (MITO END-2) reported a significant increase in PFS from 8.7 to 13 months with the addition of bevacizumab to upfront carboplatin and paclitaxel chemotherapy, although these results have not been published in full. 134 However, at this time, no antiangiogenic agents are FDA-approved for endometrial cancer.…”

Section: Antiangiogenic Therapymentioning

confidence: 99%

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Current recommendations and recent progress in endometrial cancer

Brooks

Fleming

Lastra

et al. 2019

CA A Cancer J Clinicians

463

372

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Endometrial cancer is the most common gynecologic cancer in the United States, and its incidence is rising. Although there have been significant recent advances in our understanding of endometrial cancer biology, many aspects of treatment remain mired in controversy, including the role of surgical lymph node assessment and the selection of patients for adjuvant radiation or chemotherapy. For the subset of women with microsatellite‐instable, metastatic disease, anti– programmed cell death protein 1 immunotherapy (pembrolizumab) is now approved by the US Food and Drug Administration, and numerous trials are attempting to build on this early success.

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Section: Future Directionsmentioning

confidence: 99%

Section: Therapy For Recurrent or Metastatic Diseasementioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

Section: Therapy For Recurrent or Metastatic Diseasementioning

confidence: 99%

Section: Antiangiogenic Therapymentioning

confidence: 99%

See 3 more Smart Citations

Current recommendations and recent progress in endometrial cancer

Brooks

Fleming

Lastra

et al. 2019

CA A Cancer J Clinicians

463

372

View full text Add to dashboard Cite

show abstract

PI3K/AKT/mTOR inhibitors for advanced or recurrent endometrial cancer

Roncolato

Lindemann

Willson

et al. 2019

Cochrane Database of Systematic Reviews

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Endometrial Cancer

Westin¹,

Lu²,

Rahaman³

2022

Holland‐Frei Cancer Medicine

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Overview Endometrial carcinoma is the most frequent gynecologic cancer in the United States with over 65,000 new cases diagnosed per year. Over 80% have the classic estrogen‐dependent endometrioid histology with a favorable prognosis. Nonendometrioid histology types, including uterine serous carcinomas (USC), carcinosarcomas, and clear cell carcinomas, have a different molecular profile associated with more virulent disease and diminished survival. The Cancer Genome Atlas (TCGA) has defined four molecular subtypes of endometrial cancer, based on somatic mutations, copy number alterations, and microsatellite instability status. Over 75% of patients present with irregular or post‐menopausal bleeding. Surgical staging includes a hysterectomy, bilateral salpingo‐oophorectomy, with or without pelvic and para‐aortic lymph node sampling done via a laparotomy, laparoscopy, or robotic surgery. Surgery, where possible, constitutes the definitive primary treatment for most patients with endometrial carcinoma. Primary radiation therapy and primary hormonal therapy are alternatives for inoperable patients. Adjuvant therapy for stage I disease is determined by age, depth of myometrial invasion, lymph‐vascular space invasion, and tumor grade. For patients with advanced and recurrent disease radiation therapy, chemotherapy, and hormonal therapy are utilized. The combination of paclitaxel and carboplatin is the most effective and tolerable chemotherapy combination and currently serves as the backbone for a number of investigational strategies. Immune check‐point inhibitors are FDA approved for the treatment of metastatic endometrial cancer, including pembrolizumab alone for microsatellite instability‐high (MSI‐H) cancers and pembrolizumab and lenvatinib for microsatellite stable (MSS) disease. The growing understanding of the molecular aberrations common in endometrial cancer has led to exploration of a number of therapies, targeting angiogenesis and the PI3K/AKT, HER2, RAS/RAF, and DNA damage repair pathways.

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A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer

Abstract: PFS was not significantly increased in any experimental arm compared to historical controls. NRG Oncology/Gynecologic Oncology Group Study GOG-86P.

Cited by 122 publications

References 27 publications

Current recommendations and recent progress in endometrial cancer

Current recommendations and recent progress in endometrial cancer

PI3K/AKT/mTOR inhibitors for advanced or recurrent endometrial cancer

Endometrial Cancer

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