Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer

Colombo, Nicoletta; Dubot, Coraline; Lorusso, Domenica; Caceres, M. Valeria; Shapira-Frommer, Ronnie; Tewari, Krishnansu S.; Salman, Pamela; Usta, Edwin Hoyos; Yáñez, Eduardo; Gümüş, Mahmut; Mendoza, Mivael Olivera Hurtado de; Samouëlian, Vanessa; Castonguay, Vincent; Архипов, А. В.; Toker, Sarper; Li, Kan; Keefe, Stephen Michael; Monk, Bradley J.

doi:10.1097/01.ogx.0000805152.09501.f1

Cited by 3 publications

(2 citation statements)

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“…Given the current situation, many patients are expected to undergo multigene panel testing for recurrence after the standard treatment around the second-line. Recently, following the results of KEYNOTE-826 [17], treatment with additional ICIs and cytotoxic chemotherapeutic agents for patients with advanced or relapsed cervical cancer has been covered by insurance in Japan. In addition to pembrolizumab, ICIs such as cemiplimab [18][19] and dual checkpoint blockades such as balstilimab plus zalifrelimab [20] and the human anti-tissue factor antibody of tisotumab vedotin [21] are gaining attention.…”

Section: Discussionmentioning

confidence: 99%

Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer

Kitazawa,

Chiyoda,

Nakamura

et al. 2023

Int J Clin Oncol

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BackgroundJapan's health insurance covers multigene panel testing. This study aimed to determine the potential availability and utility of gene panel testing clinically in gynecologic oncology. MethodsWe analyzed the characteristics of patients with gynecologic cancer who underwent gene panel testing using FoundationOne® CDx or OncoGuide™ NCC Oncopanel between November 2019 and October 2022. ResultsOut of 102 patients analyzed, 32, 18, 43, 8, and 1 had cervical, endometrial, ovarian cancers, sarcoma, and vaginal cancer, respectively. Druggable gene alteration was found in 70 patients (68.6%; 21 with cervical cancer, 15 with endometrial cancer, 28 with ovarian cancer, 5 with sarcoma, and 1 with others). The most common druggable gene alteration was PIK3CA mutation (n = 21), followed by PTEN mutation (n = 12) and high tumor mutation burden (TMB-H) (n = 11). TMB-H was detected in 5 patients with cervical cancer, 5 with endometrial cancer, and 1 with endometrial stromal sarcoma. Eleven patients (10.8%) received molecularly targeted therapy according to their gene aberrations. Gene panel testing was mostly performed when the second-line treatment was ineffective. Of all 102 patients, 60 did not have recommended treatment, and 15 died or had worsened conditions before obtaining the test results. ConclusionThrough multigene panel testing, although many patients had druggable gene alterations, 10.8% of them received the recommended treatment. TMB-H was mainly observed in cervical/endometrial cancer, suggesting its potential as a therapeutic biomarker of immune checkpoint inhibitors. Furthermore, patients' prognosis and performance status should be considered before performing the test.

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Section: Discussionmentioning

confidence: 99%

Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer

Kitazawa,

Chiyoda,

Nakamura

et al. 2023

Int J Clin Oncol

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“…Nivolumab is an anti-PD1 monoclonal antibody, first approved by FDA in 2014 for treatment of melanoma patients, and later shown in clinical trials to benefit patients with different cancer types, including malignant melanoma, non-small cell lung cancer, renal cancer, gastric cancer, cervical cancer, hepatocellular carcinoma, and MSI positive colorectal cancer [266,267]. Pembrolizumb is another anti-PD1 monoclonal antibody approved for treatment of cervical cancer [268], esophageal cancer [269], gastric cancer [270], non-small cell lung cancer [271], colorectal cancer [272] and other types of cancer [273]. Recently, a novel anti-PD1 antibody, cemiplimab, was approved for treatment of metastatic cutaneous squamous cell carcinoma in 2018 [274].…”

Section: Immune Checkpoint Activation In the Tmementioning

confidence: 99%

Immunoregulatory signal networks and tumor immune evasion mechanisms: insights into therapeutic targets and agents in clinical development

Qian

Taskén

2022

Biochemical Journal

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Through activation of immune cells, the immune system is responsible for identifying and destroying infected or otherwise damaged cells including tumorigenic cells that can be recognized as foreign, thus maintaining homeostasis. However, tumor cells have evolved several mechanisms to avoid immune cell detection and killing, resulting in tumor growth and progression. In the tumor microenvironment, tumor infiltrating immune cells are inactivated by soluble factors or tumor promoting conditions and lose their effects on tumor cells. Analysis of signaling and crosstalk between immune cells and tumor cells have helped us to understand in more detail the mechanisms of tumor immune evasion and this forms basis for drug development strategies in the area of cancer immunotherapy. In this review, we will summarize the dominant signaling networks involved in immune escape and describe the status of development of therapeutic strategies to target tumor immune evasion mechanisms with focus on how the tumor microenvironment interacts with T cells.

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Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer

Kitazawa

Chiyoda

Nakamura

et al. 2023

Preprint

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Background Japan’s health insurance covers multigene panel testing. This study aimed to determine the potential availability and utility of gene panel testing clinically in gynecologic oncology.Methods We analyzed the characteristics of patients with gynecologic cancer who underwent gene panel testing using FoundationOne® CDx or OncoGuide™ NCC Oncopanel between November 2019 and October 2022.Results Out of 102 patients analyzed, 32, 18, 43, 8, and 1 had cervical, endometrial, ovarian cancers, sarcoma, and vaginal cancer, respectively. Druggable gene alteration was found in 70 patients (68.6%; 21 with cervical cancer, 15 with endometrial cancer, 28 with ovarian cancer, 5 with sarcoma, and 1 with others). The most common druggable gene alteration was PIK3CA mutation (n = 21), followed by PTEN mutation (n = 12) and high tumor mutation burden (TMB-H) (n = 11). TMB-H was detected in 5 patients with cervical cancer, 5 with endometrial cancer, and 1 with endometrial stromal sarcoma. Eleven patients (10.8%) received molecularly targeted therapy according to their gene aberrations. Gene panel testing was mostly performed when the second-line treatment was ineffective. Of all 102 patients, 60 did not have recommended treatment, and 15 died or had worsened conditions before obtaining the test results.Conclusion Through multigene panel testing, although many patients had druggable gene alterations, 10.8% of them received the recommended treatment. TMB-H was mainly observed in cervical/endometrial cancer, suggesting its potential as a therapeutic biomarker of immune checkpoint inhibitors. Furthermore, patients’ prognosis and performance status should be considered before performing the test.

show abstract

Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer

Cited by 3 publications

References 0 publications

Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer

Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer

Immunoregulatory signal networks and tumor immune evasion mechanisms: insights into therapeutic targets and agents in clinical development

Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer

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