Pembrolizumab Produces Promising Antitumor Activity in Cervical Cancer Study

According to results from a phase Ib study, pembrolizumab (Keytruda) was well tolerated and demonstrated promising antitumor activity in patients with PD-L1–positive advanced cervical squamous cell cancer.

Jean-Sebastien Frenel, MD

Jean-Sebastien Frenel, MD

According to results from a phase Ib study, pembrolizumab (Keytruda) was well tolerated and demonstrated promising antitumor activity in patients with PD-L1—positive advanced cervical squamous cell cancer.

The cervical cancer cohort from the KEYNOTE-028 study, presented earlier this year at the 2016 ASCO Annual Meeting, included 24 patients, 23 of whom were evaluable. The overall response rate (ORR) was 12.5% in these patients, with a median duration of response of 19.3 weeks, and a median time to response of 8 weeks. The stable disease rate was 12.5%, and the median duration of stable disease was 19.6 weeks.

Thirty-eight percent of patients had a decrease in target lesions. By the time of the data cutoff, all patients in the study had progressed and discontinued treatment.

In order to be eligible for enrollment in KEYNOTE-028, patients had to have unresectable or metastatic cervical cancer, and they had to have failed or been unable to receive standard therapy. Patients were required to have an ECOG PS of 0 or 1, measurable disease per RECIST 1.1, and PD-L1—positive tumors.

Sixty-three percent of patients had metastatic disease, while the remaining had locally advanced disease. Most patients in the study had received some form of prior therapy.

“About 96% of patients received prior radiotherapy, and this was quite a heavily pretreated population, as most of the patients had received at least 2 lines of chemotherapy for advanced disease,” lead study author Jean-Sebastien Frenel, MD, of Institut de Cancérologie de l’Ouest, said when presenting the data at ASCO.

Eligible patients received 10 mg/kg of pembrolizumab intravenously every 2 weeks during the study, until disease progression or unacceptable toxicity. Responses were assessed every 8 weeks for the first 6 months, and every 12 weeks thereafter.

The primary endpoints of this study were ORR per RECIST 1.1 and safety. The secondary endpoints of the study included progression-free survival (PFS), overall survival (OS), and duration of response.

The 6-month PFS rate was 13%, and the 6-month OS rate was 66.7%. The median OS was 9 months.

The safety profile observed in this study was consistent with adverse-event data reported for pembrolizumab in other tumor types. Eighteen patients (75%) experienced a treatment-related adverse event, with pyrexia and rash occurring in more than 10% of patients.

Five patients (20.8%) had grade 3 treatment-related adverse events, and 2 of those patients discontinued their use of pembrolizumab. No grade 4 or 5 treatment-related adverse events occurred.

Bevacizumab, in combination with chemotherapy, is approved as a first-line therapy for advanced cervical cancer. However, there is still a large, unmet need for effective treatments.

“There are limited treatment options after progression on first-line therapy, and many of these patients are platinum-resistant. Patients are encouraged to enroll in clinical trials,” Frenel noted.

Currently, despite the available treatments, the median survival for patients with metastatic or recurrent cervical cancer is approximately 7 months.

Both the safety profile and the clinical benefit of pembrolizumab in advanced cervical cancer are currently being investigated further in the phase II, multicohort KEYNOTE-158 trial (NCT02628067).

Pembrolizumab, as an anti—PD-1 antibody, can block the interaction between PD-1 and its ligands. The agent has demonstrated antitumor activity in a wide range of advanced cancers, and currently has FDA-approved indications for non-–small cell lung cancer, head and neck cancer, and melanoma.


Frenel JS, Le Tourneau C, O’Neil BH, et al. Pembrolizumab in patients with advanced cervical squamous cell cancer: preliminary results from the phase Ib KEYNOTE-028 study.J Clin Oncol34, 2016 (suppl; abstr 5515).

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