Pattern of disease and response to pembrolizumab in recurrent cervical cancer.

Cervical cancer Immune checkpoint blockade PD-1 resistance Tumor microenvironment

Journal

Gynecologic oncology reports
ISSN: 2352-5789
Titre abrégé: Gynecol Oncol Rep
Pays: Netherlands
ID NLM: 101652231

Informations de publication

Date de publication:
Aug 2021
Historique:
received: 21 05 2021
revised: 28 06 2021
accepted: 06 07 2021
entrez: 4 8 2021
pubmed: 5 8 2021
medline: 5 8 2021
Statut: epublish

Résumé

Since the approval of pembrolizumab for advanced or recurrent PD-L1 positive (CPS > 1%) cervical cancer, the clinical characteristics associated with response have remained undefined. We sought to characterize the clinicopathologic features of patients with advanced cervical cancer at our institution who derived durable clinical benefit from treatment with pembrolizumab. We conducted a retrospective cohort study of 14 patients with recurrent or metastatic cervical cancer who received pembrolizumab monotherapy from August 2017 to November 2019 and were followed until November 1, 2020. Reviewed clinical data included age, histology, tumor molecular profiling results, stage at diagnosis, treatment history, baseline pattern of metastatic disease at initiation of anti-PD-1 therapy, and outcomes. Treatment response was evaluated by computed tomography using RECIST v1.1 criteria. The objective response rate was 21% (n = 3), including two partial responses and one complete response. Two patients (14%) had stable disease of six months or greater, for an observed durable clinical benefit rate of 36%. When stratified by those who derived clinical benefit, metastatic spread to lung and/or lymph node only at baseline was associated with improved response to pembrolizumab (n = 7, p = 0.02) and associated with significantly improved PFS and OS. Tumor mutational burden was higher in those with durable clinical benefit compared to non-responders (median 12.7 vs. 3.5 mutations/megabase, p = 0.03). Our findings highlight clinical features that may select for a population most likely to benefit from pembrolizumab monotherapy and underscores the need for identification of additional biomarkers of response.

Identifiants

pubmed: 34345644
doi: 10.1016/j.gore.2021.100831
pii: S2352-5789(21)00135-1
pmc: PMC8319446
doi:

Types de publication

Journal Article

Langues

eng

Pagination

100831

Subventions

Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States

Informations de copyright

© 2021 The Authors. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Auteurs

Kathryn M Miller (KM)

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Olga T Filippova (OT)

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Sara A Hayes (SA)

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Nadeem R Abu-Rustum (NR)

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Surgery, Weill Cornell Medical College, New York, NY, United States.

Carol Aghajanian (C)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Medicine, Weill Cornell Medical College, New York, NY, United States.

Vance Broach (V)

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Surgery, Weill Cornell Medical College, New York, NY, United States.

Lora H Ellenson (LH)

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Pier Selenica (P)

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Elizabeth L Jewell (EL)

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Surgery, Weill Cornell Medical College, New York, NY, United States.

Chrisann Kyi (C)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Medicine, Weill Cornell Medical College, New York, NY, United States.

Yuliya Lakhman (Y)

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Jennifer J Mueller (JJ)

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Surgery, Weill Cornell Medical College, New York, NY, United States.

Roisin E O'Cearbhaill (RE)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Medicine, Weill Cornell Medical College, New York, NY, United States.

Kay J Park (KJ)

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Yukio Sonoda (Y)

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Surgery, Weill Cornell Medical College, New York, NY, United States.

Dmitriy Zamarin (D)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Medicine, Weill Cornell Medical College, New York, NY, United States.

Britta Weigelt (B)

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Mario M Leitao (MM)

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Surgery, Weill Cornell Medical College, New York, NY, United States.

Claire F Friedman (CF)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Medicine, Weill Cornell Medical College, New York, NY, United States.

Classifications MeSH