KEYNOTE-158: Pembrolizumab in Previously Treated Advanced Cervical Cancer


Key Points

  • Pembrolizumab was associated with an objective response rate of 14.6% among patients with PD-L1–positive disease.
  • Responses were observed only in patients with PD-L1–positive disease.

As reported in the Journal of Clinical Oncology by Chung et al, the phase II KEYNOTE-158 trial showed activity of pembrolizumab in previously treated programmed cell death ligand 1 (PD-L1)-positive advanced cervical cancer. The study supported the 2018 accelerated approval of pembrolizumab in this setting.

Study Details

KEYNOTE-158 is a basket trial in multiple cancer types. The current report is an interim report on the cohort of 98 patients with previously treated advanced cervical cancer.

These 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 then every 12 weeks thereafter. The primary endpoint was objective response rate on RECIST v1.1 assessed by independent central radiologic review.

Patients had a median age of 46 years (range = 24–75 years). Eighty-two patients (83.7%) had PD-L1–positive tumors (combined positive score ≥ 1), and 77 in the PD-L1–positive group had previously received ≥ 1 line of chemotherapy for recurrent or metastatic disease.

Response Rates

Median follow-up was 10.2 months. Objective response was observed in 12 patients (12.2%), including 3 with complete response. All responses occurred among the 82 patients with PD-L1–positive tumors (response rate = 14.6%), and 11 responses occurred among the 77 of these patients (14.3%) who had received ≥ 1 line of chemotherapy for recurrent or metastatic disease. In the PD-L1–positive group, median time to response was 2.1 months. Median duration of response was not reached (range = ≥ 3.7 to ≥ 18.6 months), with response in 7 patients lasting ≥ 12 months at time of analysis.  Median progression-free survival was 2.1 months in both the entire population and the PD-L1–positive population. Median overall survival was 9.4 in the total population vs 11.0 months in the PD-L1–positive population.

Adverse Events

Treatment-related adverse events of any grade occurred in 65.3% of patients, with the most common being hypothyroidism (10.2%), decreased appetite (9.2%), and fatigue (9.2%). Treatment-related grade 3 or 4 adverse events occurred in 12.2% of patients, with the most common being increased alanine transaminase (3.1%). Treatment-related adverse events led to discontinuation of treatment in 4 patients (4.1%).

Immune-mediated adverse events occurred in 25.5% of patients, with grade 3 or 4 events occurring in 5.1% (hepatitis in 2 patients, severe skin reaction in 2 patients, and adrenal insufficiency in 1 patient). The most common immune-mediated adverse events of any grade were hypothyroidism (11.2%) and hyperthyroidism (9.2%). No treatment-related deaths were reported.

The investigators concluded, “Pembrolizumab monotherapy demonstrated durable antitumor activity and manageable safety in patients with advanced cervical cancer. On the basis of these results, the U.S. 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.”

Hyun Cheol Chung, MD, PhD, of the Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Merck Sharp & Dohme, a subsidiary of Merck & Co. The study authors’ full disclosures can be found at

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