Response to pembrolizumab in a heavily treated patient with metastatic ovarian carcinosarcoma

Molin, Graziela Zibetti Dal; Abrahão, Carina Meira; Coleman, Robert L.; Maluf, Fernando C.

doi:10.1186/s40661-018-0063-3

Cited by 16 publications

(9 citation statements)

References 22 publications

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“…While there have been no large clinical trials investigating response to immunotherapy in gynecologic carcinosarcomas, rare cases demonstrating good clinical response to pembrolizumab have been documented (38,39). Interestingly, one of these cases was found to have a POLE mutation which likely explains the clinical success with pembrolizumab therapy (39).…”

Section: Discussionmentioning

confidence: 99%

PD-L1 and Mismatch Repair Status in Uterine Carcinosarcomas

Jenkins

Cantrell

Stoler

et al. 2020

International Journal of Gynecological Pathology

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Uterine carcinosarcomas have few adjuvant treatment options. Programmed cell death ligand-1 (PD-L1) expression in these tumors may predict response to checkpoint inhibitor therapies. An increase in PD-L1 expression has been shown in endometrial carcinomas with mismatch repair (MMR) deficiencies; however, few studies have evaluated PD-L1 expression in uterine carcinosarcomas. We examined PD-L1 expression in 41 cases of uterine carcinosarcoma using combined positive scores (CPS) and tumor proportion scores (TPS), and correlated with MMR status, p53 expression, and epithelial histotype. In addition to confirming the diagnosis of carcinosarcoma, the epithelial components were stratified based on endometrioid versus serous histology. Thirty-three cases (80%) were positive for PD-L1, defined as a CPS score of ≥ 1 or a TPS score of ≥ 1%. Twelve cases (29%) showed high expression of PD-L1, defined as a CPS score of ≥ 10 or a TPS score of ≥ 10%. The majority of the morphologically adjudicated carcinosarcomas had a serous epithelial component (83%) rather than endometrioid (17%), which was reinforced by aberrant p53 staining predominantly within cases with serous morphology. The majority of carcinosarcomas showed at least focal PD-L1 expression, predominantly in tumor-associated immune cells. Carcinosarcomas with endometrioid morphology were significantly more likely to have high-level PD-L1 (5/7 vs. 7/34; P = 0.015). MMR-deficient carcinosarcomas were also more likely to have high-level PD-L1 (2/3 vs. 10/28); however, this did not reach statistical significance (P = 0.2) and overall MMR-deficiency was uncommon (3 cases, 7%). These findings suggest that PD-L1 may be additive to MMR testing as a predictive biomarker for checkpoint inhibitor vulnerability in carcinosarcomas.

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Section: Discussionmentioning

confidence: 99%

PD-L1 and Mismatch Repair Status in Uterine Carcinosarcomas

Jenkins

Cantrell

Stoler

et al. 2020

International Journal of Gynecological Pathology

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“…Targeting VEGF to inhibit angiogenesis could be a potential treatment strategy for OCS. Multiple case reports cite the use of bevacizumab as a treatment for OCS 51–53 . One study analyzed retrospective data for patients with a gynecologic carcinosarcoma treated with Pazopanib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and receptor tyrosine kinase c-KIT.…”

Section: Discussionmentioning

confidence: 99%

“…Positron emission tomography /computed tomography showed partial response in affected lymph nodes after multiple cycles of pembrolizumab, with only thyroiditis grade 1 reported as an adverse event. Of note, this patient was not tested for microsatellite instability, mutational load, or PD-L1 expression 51 . Another female with Lynch syndrome and stage III OCS was started on pembrolizumab after previously showing disease progression on chemotherapy and bevacizumab.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple case reports cite the use of bevacizumab as a treatment for OCS. [51][52][53] One study analyzed retrospective data for patients with a gynecologic carcinosarcoma treated with Pazopanib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and receptor tyrosine kinase c-KIT. Of the 2 patients included with OCS, 1 patient had progression-free survival (PFS) of 11 months and an overall survival of 12.4 months, similar to prognosis for OCS patients treated with chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

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Genomic and Molecular Characteristics of Ovarian Carcinosarcoma

Ramphal,

Hadfield,

Bandera

et al. 2023

American Journal of Clinical Oncology

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Ovarian carcinosarcoma (OCS) is a rare malignancy with a poor prognosis. It is a biphasic tumor with malignant epithelial and mesenchymal components. A few mutations commonly seen in cancer have been identified in OCS, including TP53, PIK3CA, c-myc, ZNF217, ARID1A, and CTNNB1. Some OCS tumors have shown vascular endothelial growth factor positivity and limited HER2 expression. There is evidence of homologous recombination deficiency in OCS. This malignancy can be categorized as copy number high but has not been shown to have a high tumor mutational burden. There are mixed findings regarding the presence of biomarkers targeted by immune checkpoint inhibitors in OCS. For treatments other than systemic chemotherapy, the data available are largely based on in vitro and in vivo studies. In addition, there are case reports citing the use of poly-ADP ribose polymerase inhibitors, vascular endothelial growth factor inhibitors, and immunotherapy with varying degrees of success. This review paper will discuss the molecular and genomic characteristics of OCS, which can guide future treatment strategies.

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“…[ 20 ] Recently, 2 case reports have demonstrated that pembrolizumab monotherapy or combination therapy is effective to control the progress of disease including metastatic ovarian carcinosarcoma and ovarian adenosquamous carcinoma. [ 21 , 22 ] Additionally, some clinical trials have shown that pembrolizumab therapy is effective for other gynecologic cancers, including cervical and endometrial cancer. [ 23 , 24 ] In May 2017, the FDA has approved pembrolizumab for patients with unresectable or MSI-H or mismatch repair gene defects (dMMR) solid tumors that progressed following prior treatment.…”

Section: Discussionmentioning

confidence: 99%

Responses of metastatic primary fallopian tube carcinoma to pembrolizumab and nab-paclitaxel

Jiang

Chen²,

Zhu³

et al. 2020

Medicine

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Rationale: Primary fallopian tube carcinoma (PFTC) is an extremely rare but invasive malignancy with a dismal prognosis. Very few data exist on the salvage treatment for patients with PFTC. Here we report a case showing an impressive response to immunotherapy combined with chemotherapy, which have never been reported before on patients with metastatic PFTC. Patient concerns: A 42-year-old woman, who was diagnosed with PFTC in 2010, had been failed of multiple systemic therapies and antiangiogenic therapy because of the disease recurrence and progression. Diagnosis: Metastatic primary fallopian tube carcinoma. Interventions: The patient underwent surgery in May 2010 and had multi-line chemotherapies plus an anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody for about 9 years. Due to treatment failure the patient accepted the immunotherapy with the checkpoint inhibitor, pembrolizumab, combined with nab-paclitaxel from December 2018 to April 2019. Outcomes: The patient showed a complete response after 6 cycles , treatment. Thus far, the patient is taking pembrolizumab as maintenance and remains in good health. Lessons: Pembrolizumab combined with chemotherapy for treatment of PFTC may provide a positive antitumor effect in multiple metastatic lesions, but more clinical evidence is needed to confirm the efficacy and safety.

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Response to pembrolizumab in a heavily treated patient with metastatic ovarian carcinosarcoma

Cited by 16 publications

References 22 publications

PD-L1 and Mismatch Repair Status in Uterine Carcinosarcomas

PD-L1 and Mismatch Repair Status in Uterine Carcinosarcomas

Genomic and Molecular Characteristics of Ovarian Carcinosarcoma

Responses of metastatic primary fallopian tube carcinoma to pembrolizumab and nab-paclitaxel

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