A phase II study of pembrolizumab in combination with doxorubicin in advanced, recurrent or metastatic endometrial cancer

Oaknin, Ana; Pérez, María Jesús Rubio; Madrid, L. Fariñas; Redondo, Andrés; Esteban, Alfonso Yubero; Martin, M.; Martín, Antonio González; Romero, Ignacio; García-Donás, Jesús; Serrano, Raquel; Martínez, Antonio; Diez, M Ocariz; Lorenzo, Maria Luisa Sanchez; Olmedo, M D Fenor De La Maza Lopez; Freixinós, V. Rodriguez; Rodriguez, J.M. Piulats

doi:10.1093/annonc/mdz250.070

Cited by 2 publications

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“…The standard first‐line treatment for endometrial cancer is currently under evaluation in randomized Phase 3 trials in combination with different anti‐PD‐1/PD‐L1 ICIs, such as pembrolizumab (NCT03914612), atezolizumab (NCT03603184), or dostarlimab (NCT03981796). Pembrolizumab in combination with the second‐line chemotherapy doxorubicin has already shown a 31.3% ORR and a manageable safety profile 151 . Similarly, the ADELE trial (adjuvant tislelizumab [Baizean, BeiGen] plus chemotherapy after chemoradiation) plans to assess the efficacy of an ICI used in addition to standard chemoradiation and chemotherapy in patients with high‐risk MMRd endometrial cancer.…”

Section: Resultsmentioning

confidence: 99%

“…According to the TCGA study, there are significant genomic similarities between p53 abn endometrial cancer and high‐grade serous tubo‐ovarian cancer. Both types of cancer are characterized by high genomic instability, low mutation loads, and almost universal TP53 mutations 151 . These similarities suggest the hope for treating MMRp endometrial cancer with other rational combinations, such as the use of PARP inhibitors.…”

Section: Resultsmentioning

confidence: 99%

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Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies

Yang

Bao

2023

Intl J Gynecology & Obste

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BackgroundWhen determining adjuvant treatment for endometrial cancer, the decision typically relies on factors such as cancer stage, histologic grade, subtype, and a few histopathologic markers. The Cancer Genome Atlas revealed molecular subtyping of endometrial cancer, which can provide more accurate prognostic information and guide personalized treatment plans.ObjectiveTo summarize the expression and molecular basis of the main biomarkers of endometrial cancer.Search StrategyPubMed was searched from January 2000 to March 2023.Selection CriteriaStudies evaluating molecular subtypes of endometrial cancer and implications for adjuvant treatment strategies.Data Collection and AnalysisThree authors independently performed a comprehensive literature search, collected and extracted data, and assessed the methodological quality of the included studies.Main ResultsWe summarized the molecular subtyping of endometrial cancer, including mismatch repair deficient, high microsatellite instability, polymerase epsilon (POLE) exonuclease domain mutated, TP53 gene mutation, and non‐specific molecular spectrum. We also summarized planned and ongoing clinical trials and common therapy methods in endometrial cancer. POLE mutated endometrial cancer consistently exhibits favorable patient outcomes, regardless of adjuvant therapy. Genomic similarities between p53 abnormality endometrial cancer and high‐grade serous ovarian cancer suggested possible overlapping treatment strategies. High levels of immune checkpoint molecules, such as programmed cell death 1 and programmed cell death 1 ligand 1 can counterbalance mismatch repair deficient endometrial cancer immune phenotype. Hormonal treatment is an appealing option for high‐risk non‐specific molecular spectrum endometrial cancers, which are typically endometrioid and hormone receptor positive. Combining clinical and pathologic characteristics to guide treatment decisions for patients, including concurrent radiochemotherapy, chemotherapy, inhibitor therapy, endocrine therapy, and immunotherapy, might improve the management of endometrial cancer and provide more effective treatment options for patients.ConclusionsWe have characterized the molecular subtypes of endometrial cancer and discuss their value in terms of a patient‐tailored therapy in order to prevent significant under‐ or overtreatment.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies

Yang

Bao

2023

Intl J Gynecology & Obste

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“…Ongoing research and clinical trials are crucial to improve outcomes and patient care in EC by optimizing the selection of appropriate combination therapies, identifying predictive biomarkers, and developing personalized treatment strategies (Table 1) [174]. Immunotherapy + Radiotherapy Pembrolizumab after radiotherapy [175] Immunotherapy + Chemotherapy Pembrolizumab + Doxorubicin [176] Pembrolizumab + Paclitaxel + Carboplatin [177] Radiotherapy + Chemotherapy + Immunotherapy Radiotherapy + Carboplatin or Paclitaxel + Bevacizumab [138,178] Immunotherapy + Anti-angiogenic therapy Pembrolizumab + Lenvatinib [179,180] Chemotherapy + Immunotherapy + Anti-angiogenic therapy Cisplatin + Pembrolizumab + Lenvatinib [152] Immunotherapy + PAPP inhibitors Olaparib + Durvalumab [181,182] Anti-Her2 Therapy + Chemotherapy Trastuzumab + Carboplatin + Paclitaxel [183] With increased clinical experience and supported by advanced scientific research, tumor immunotherapy can be better understood, leading to an innovative and safe approach to treating cancer patients.…”

Section: Immunotherapymentioning

confidence: 99%

Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy

Bostan,

Mihaila,

Roman

et al. 2024

Cancers

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Endometrial cancer is one the most prevalent gynecological cancers and, unfortunately, has a poor prognosis due to low response rates to traditional treatments. However, the progress in molecular biology and understanding the genetic mechanisms involved in tumor processes offers valuable information that has led to the current classification that describes four molecular subtypes of endometrial cancer. This review focuses on the molecular mechanisms involved in the pathogenesis of endometrial cancers, such as genetic mutations, defects in the DNA mismatch repair pathway, epigenetic changes, or dysregulation in angiogenic or hormonal signaling pathways. The preclinical genomic and molecular investigations presented allowed for the identification of some molecules that could be used as biomarkers to diagnose, predict, and monitor the progression of endometrial cancer. Besides the therapies known in clinical practice, targeted therapy is described as a new cancer treatment that involves identifying specific molecular targets in tumor cells. By selectively inhibiting these targets, key signaling pathways involved in cancer progression can be disrupted while normal cells are protected. The connection between molecular biomarkers and targeted therapy is vital in the fight against cancer. Ongoing research and clinical trials are exploring the use of standard therapy agents in combination with other treatment strategies like immunotherapy and anti-angiogenesis therapy to improve outcomes and personalize treatment for patients with endometrial cancer. This approach has the potential to transform the management of cancer patients. In conclusion, enhancing molecular tools is essential for stratifying the risk and guiding surgery, adjuvant therapy, and cancer treatment for women with endometrial cancer. In addition, the information from this review may have an essential value in the personalized therapy approach for endometrial cancer to improve the patient’s life.

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A phase II study of pembrolizumab in combination with doxorubicin in advanced, recurrent or metastatic endometrial cancer

Cited by 2 publications

References 0 publications

Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies

Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies

Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy

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