Reference Detail

Ref Type

Journal Article

PMID

(30943124)

Authors

Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, Manzuk L, Piha-Paul SA, Xu L, Zeigenfuss S, Pruitt SK, Leary A

Title

Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology	37	17	2019 06 10	1470-1478	J Clin Oncol

URL

Abstract Text

KEYNOTE-158 ( ClinicalTrials.gov identifier: NCT02628067) is a phase II basket study investigating the antitumor activity and safety of pembrolizumab in multiple cancer types. We present interim results from patients with previously treated advanced cervical cancer.Patients received pembrolizumab 200 mg every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision. Tumor imaging was performed every 9 weeks for the first 12 months and every 12 weeks thereafter. The primary end point was objective response rate (ORR), assessed per Response Evaluation Criteria in Solid Tumors (version 1.1) by independent central radiologic review. Safety was a secondary end point.Ninety-eight patients were treated. Median age was 46.0 years (range, 24 to 75 years), and 65.3% of patients had Eastern Cooperative Oncology Group performance status of 1. Eighty-two patients (83.7%) had programmed death-ligand 1 (PD-L1)-positive tumors (combined positive score ≥ 1), 77 having previously received one or more lines of chemotherapy for recurrent or metastatic disease. Median follow-up was 10.2 months (range, 0.6 to 22.7 months). ORR was 12.2% (95% CI, 6.5% to 20.4%), with three complete and nine partial responses. All 12 responses were in patients with PD-L1-positive tumors, for an ORR of 14.6% (95% CI, 7.8% to 24.2%); 14.3% (95% CI, 7.4% to 24.1%) of these responses were in those who had received one or more lines of chemotherapy for recurrent or metastatic disease. Median duration of response was not reached (range, ≥ 3.7 to ≥ 18.6 months). Treatment-related adverse events occurred in 65.3% of patients, and the most common were hypothyroidism (10.2%), decreased appetite (9.2%), and fatigue (9.2%). Treatment-related grade 3 to 4 adverse events occurred in 12.2% of patients.Pembrolizumab monotherapy demonstrated durable antitumor activity and manageable safety in patients with advanced cervical cancer. On the basis of these results, the US Food and Drug Administration granted accelerated approval of pembrolizumab for patients with advanced PD-L1-positive cervical cancer who experienced progression during or after chemotherapy.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CD274 positive	cervical cancer	sensitive	Pembrolizumab	FDA approved - On Companion Diagnostic	Actionable	In a Phase II trial (KEYNOTE-158) that supported FDA approval, treatment with Keytruda (pembrolizumab) resulted in an objective response rate of 14.6% (12/82) in patients with CD274 (PD-L1)-positive (CPS >=1) advanced cervical cancer, including 3 with a complete response and 9 with a partial response (PMID: 30943124; NCT02628067).	30943124 detail... detail...