Lenvatinib plus pembrolizumab in patients with advanced or recurrent uterine carcinosarcoma

Hunt, Jonathan; Chambers, Laura M.; Yao, Meng; Joehlin‐Price, Amy; Debernardo, Robert; Rose, Peter G.

doi:10.1016/j.gore.2021.100840

Cited by 6 publications

(6 citation statements)

References 24 publications

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“…The ORR for the 20 patients was 60.0%, and 2 of 6 patients with UCS exhibited a response. An initial small retrospective case series by Hunt et al [24] that included 7 UCS patients with UCS treated with LEN/PEM found no partial or complete response. However, that study did not include patients who had received only one line of prior therapy.…”

Section: Discussionmentioning

confidence: 99%

High Effectiveness of Lenvatinib Plus Pembrolizumab in the NSMP/MMRd Molecular Subtype of Endometrial Cancer: A Real-World Data Analysis

Chiba

Kagabu

Osakabe

et al. 2023

Preprint

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Background: The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) has identified four risk groups for the prognosis of endometrial cancer (EC). However, the prognostic impact of these subgroups on lenvatinib (LEN) plus pembrolizumab (PEM) administered as subsequent therapy after relapse is unknown. This study aimed to explore the effectiveness and safety of LEN/PEM therapy for recurrent EC using the ProMisE molecular classification. Methods:This single-center retrospective study included patients who underwent LEN/PEM therapy at Iwate Medical University Hospital between January 2022 and March 2023. Formalin-fixed paraffin-embedded specimens obtained from patients before treatment were collected and classified into the mismatch repair-deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP) subtypes using immunohistochemistry (IHC). The response rate, progression-free survival (PFS), and adverse events were evaluated using electronic medical records. The study was approved by the hospital’s ethics committee (approval number: MH2022-093). Results: This study enrolled 20 patients, who underwent a median follow-up of 10.7 months [95% confidence interval (CI): 8.9-12.4]. The best overall response rate was 60.0% (36.1–80.9) and the median PFS was 9.3 months (4.4-14.3). The median PFS in the p53abn group (n=8) was 3.2 months (2.3-4.2); however, PFS did not reach the median (p = 0.001) in the MMRd/NSMP group (n=12). Symptomatic immune-related adverse events (except hypothyroidism) occurred in 4/20 (25.0%) patients, and a response was observed in all cases, irrespective of the molecular subtype. No treatment-related deaths occurred. Conclusion: The IHC-based ProMisE molecular classification system provides useful information for patient selection for LEN/PEM therapy.

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Section: Discussionmentioning

confidence: 99%

High Effectiveness of Lenvatinib Plus Pembrolizumab in the NSMP/MMRd Molecular Subtype of Endometrial Cancer: A Real-World Data Analysis

Chiba

Kagabu

Osakabe

et al. 2023

Preprint

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“…Unfortunately, no UCS was included in KEYNOTE-775. Hunt et al presented a small retrospective series with pembrolizumab and lenvatinib in seven patients of advanced or recurrent UCS as ≥ third-line, which observed no partial or complete response [ 40 ], while it was unknown if used earlier at first relapse. A ROCSAN trial with an anti-PD1 (dostarlimab) and a PARPi (niraparib) is now recruiting [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Management and Prognosis of Patients with Recurrent or Persistent/Progressive Uterine Carcinosarcoma

et al. 2022

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Uterine carcinosarcoma (UCS) is a highly aggressive gynecologic malignancy. Recurrent or persistent/progressive disease is usually fatal. We aimed to investigate the management and prognosis of these patients. Clinical records of UCS patients from June 1987 to April 2020 were retrospectively reviewed. The stage was re-assigned with the FIGO 2009 staging system. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). Of the 168 patients, 98 experienced treatment failure. The median time to treatment failure (TTF) was 8.1 months (range: 0.0–89.1). The median follow-up time of censored patients was 32.0 months (range: 16.8–170.7). The 5-year SAR rates of those with recurrent or persistent/progressive disease were 7.6%. On multivariate analysis, salvage therapy mainly using radiotherapy (HR 0.27, 95% CI: 0.10–0.71) or chemotherapy (HR 0.41, 95% CI: 0.24–0.72) or chemoradiotherapy (CRT) (HR 0.33, 95% CI: 0.15–0.75) were associated with improved SAR, whereas disseminated recurrence was associated with significantly worse SAR (HR 3.94, 95% CI: 1.67–9.31, p = 0.002). Salvage therapy using radiotherapy or chemotherapy or CRT significantly improved SAR. Surgery significantly improved CSS but not SAR, adjusting for confounding factors.

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“…Moreover, around 10% of endometrial carcinosarcomas are MSI-H, ~5% are POLE mutated, and~60% show PD-1/PD-L1 immunohistochemical expression; immunotherapy (alone or in combination with tyrosine kinase inihibitor) may be particularly promising in these molecular subgroups 3 4 21–27. Nevertheless, to date, only anecdotal evidence exists 108 109…”

Section: Novel Therapeutic Agents and Future Perspectivesmentioning

confidence: 99%

“…108 109 A small retrospective series including seven patients (14% MSI-H/MMRd) tested the efficacy of the pembrolizumab/lenvatinib doublet in endometrial carcinosarcoma and showed no partial or complete responses. 109 One case report described a partial response with pembrolizumab used in a heavily pretreated patient with POLE mutated endometrial carcinosarcoma. 110 Another case of a patient with platinum-refractory, PD-L1-positive, MSI-H endometrial carcinosarcoma is described.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Endometrial carcinosarcoma

Bogani

Ray‐Coquard

Concin

et al. 2022

Int J Gynecol Cancer

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Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion ofPOLEand microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.

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Lenvatinib plus pembrolizumab in patients with advanced or recurrent uterine carcinosarcoma

Cited by 6 publications

References 24 publications

High Effectiveness of Lenvatinib Plus Pembrolizumab in the NSMP/MMRd Molecular Subtype of Endometrial Cancer: A Real-World Data Analysis

High Effectiveness of Lenvatinib Plus Pembrolizumab in the NSMP/MMRd Molecular Subtype of Endometrial Cancer: A Real-World Data Analysis

Management and Prognosis of Patients with Recurrent or Persistent/Progressive Uterine Carcinosarcoma

Endometrial carcinosarcoma

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