Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer

Mirza, Mansoor Raza; Chase, Dana M.; Slomovitz, Brian M.; Christensen, René dePont; Novàk, Zoltán; Black, Destin; Gilbert, Lucy; Sharma, Sudarshan; Valabrega, Giorgio; Landrum, Lisa M.; Hanker, Lars; Stuckey, Ashley; Boere, Ingrid; Gold, Michael A.; Auranen, Annika; Pothuri, Bhavana; Cibula, David; McCourt, Carolyn K.; Raspagliesi, Francesco; Shahin, Mark S.; Gill, Sarah; Monk, Bradley J.; Buscema, Joseph; Herzog, Thomas J.; Copeland, Larry J.; Tian, Mei; He, Z.C.; Stevens, Shadi; Zografos, Eleftherios; Coleman, Robert L.; Powell, Matthew A.

doi:10.1056/nejmoa2216334

Cited by 277 publications

(197 citation statements)

References 37 publications

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“…The phase 3 results build on and confirm the prior benefit of MIRV in this setting, as shown in the single-arm SORAYA trial, 2 which led to its accelerated approval by the US Food and Drug Administration. 3 That trial showed consistently clinically meaningful antitumor activity with an ORR of 32.4% at a median follow-up of 13.4 months in all 105 patients and a median duration of response of 6.9 months.…”

Section: New Standard Of Care For Platinum-resistant Ovarian Cancermentioning

confidence: 53%

“…The study found an ORR of 35.3% in patients with one to two prior therapies and an ORR of 30.2% in patients with three prior therapies as well as an ORR of 38% in patients with prior PARP inhibitor exposure and an ORR of 27.5% in patients without exposure. 2 The MIRASOL study was designed to support approval of MIRV worldwide and included 453 patients randomized 1:1 to MIRV or the investigator's choice of chemotherapy. The baseline characteristics of the treatment arms were similar, with 14% of the patients receiving one line of prior therapy, 30% receiving two lines, and 47% receiving three lines.…”

Section: New Standard Of Care For Platinum-resistant Ovarian Cancermentioning

confidence: 99%

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Combination therapy may create a practice change for advanced or recurrent endometrial cancer

Nierengarten¹

2023

Cancer

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This news section offers Cancer readers timely information on events, public policy analysis, topical issues, and personalities. In this issue, two new studies show the value of adding immunotherapy to standard‐of‐care chemotherapy to improve progression‐free survival in endometrial cancer. In addition, mirvetuximab soravtansine is confirmed as a new standard of care for platinum‐resistant ovarian cancer, and leaving ovaries during benign hysterectomies may have benefits that outweigh the potential risks of removing them.

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Section: New Standard Of Care For Platinum-resistant Ovarian Cancermentioning

confidence: 53%

Section: New Standard Of Care For Platinum-resistant Ovarian Cancermentioning

confidence: 99%

Combination therapy may create a practice change for advanced or recurrent endometrial cancer

Nierengarten¹

2023

Cancer

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“…In addition to these tumor-agnostic indications, lenvatinib (a multi-tyrosine kinase inhibitor) plus pembrolizumab was approved in Japan for advanced/recurrent endometrial cancer since December 2021, regardless of the MSI status 15 . Recently, two phase III, randomized, clinical trials showed statistically significant benefits of overall survival and/or progression-free survival in primary advanced or recurrent endometrial cancer, regardless of the status of mismatch-repair deficiency (dMMR) 16,17 . In advanced/recurrent cervical cancer, pembrolizumab in combination with platinum-based chemotherapy (with or without bevacizumab) was approved in Japan since September 2022, regardless of the PD-L1 combined positive score (CPS), based on the phase III KEYNOTE-826 trial with a statistically significant overall survival (OS) benefit 18 .…”

Section: Introductionmentioning

confidence: 99%

Genomic landscape of endometrial, ovarian and cervical cancers in Japan from database in the Center for Cancer Genomics and Advanced Therapeutics

Xi,

Kage,

Ogawa

et al. 2023

Preprint

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ObjectiveThis study aimed to comprehensively clarify genomic landscape, and its association with tumor mutation burden-high (TMB-H, ≧10 mut/Mb) and microsatellite instability-high (MSI-H) in endometrial, cervical, and ovarian cancers.MethodsWe obtained genomic datasets of a comprehensive genomic profiling test, FoundationOne® CDx, with clinical information by using the “Center for Cancer Genomics and Advanced Therapeutics” (C-CAT) database in Japan. The patients could take the tests only after the standardized treatments under universal health insurance coverage.ResultsEndometrial cancers (n=561) were characterized by high frequency of tumor mutational burden-high (TMB-H) (13.9%) and MSI-high (MSI-H) (10.8%), especially in endometrioid carcinomas. The lower ratio ofPOLEexonuclease mutations (1.4%) and higher ratio ofTP53mutations (54.4%) than previous reports suggested the prognostic impact of the molecular subtypes. Among 839 cervical cancers, frequent mutations ofKRAS(32.2%),TP53(29.4%),PIK3CA(22.2%),STK11(22.2%),CDKN2A(18.3%), andERBB2(16.7%) were observed in adenocarcinomas, while the ratio of TMB-H was significantly higher in squamous cells carcinomas (20.6%). Among 1,606 ovarian cancers, genomic profiling of serous (n=784), clear cell (n=333), endometrioid (n=92), and mucinous carcinomas (n=91) was characterized. Pathogenic mutations in thePOLEexonuclease domain were linked to high TMB (TMB >100 mut/Mb), and the mutation ratio was low in both cervical (0.0%) and ovarian cancer (0.19%).ConclusionThe C-CAT database is useful to provide mutational landscape of each cancer type and each histological subtype. As the dataset is collected exclusively from patients after the standardized treatments, the information of “druggable” alterations highlights the unmet needs for drug development in major gynecological cancers.

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“…In two randomized trials, the ICIs dostarlimab and pembrolizumab both improved progression-free survival (PFS) when added individually to carboplatin and paclitaxel; the addition of dostarlimab also demonstrated an overall survival (OS) benefit. 2,3 Greatest PFS benefits were observed in both trials among those with mismatch repair-deficiency (dMMR), and the addition of dostarlimab also demonstrated an improvement in OS rates in this subset (83 versus 59 percent at 24 months). For advanced endometrial cancer with dMMR, we now suggest the addition of either dostarlimab or pembrolizumab to chemotherapy.…”

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confidence: 99%

UpToDate®

2023

Oncology Times

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Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer

Cited by 277 publications

References 37 publications

Combination therapy may create a practice change for advanced or recurrent endometrial cancer

Combination therapy may create a practice change for advanced or recurrent endometrial cancer

Genomic landscape of endometrial, ovarian and cervical cancers in Japan from database in the Center for Cancer Genomics and Advanced Therapeutics

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