Pembrolizumab Effective for Platinum-Refractory Cervical Cancer

Patients with advanced cervical cancer face a poor prognosis. Paclitaxel and cisplatin combined with bevacizumab is the recommended first-line treatment regimen for patients with recurrent or metastatic cervical cancer. Treatment for patients progressing following first-line therapy is a high, unmet need.  Single-agent chemotherapies are commonly used in this setting, but response rates are low and of short duration. Immunotherapy with PD-1 targeting antibodies has been a highly effective treatment approach for many cancers, and in , the PD-1 inhibitor pembrolizumab was found to be active in PD-L1-positive advanced cervical cancer. The ongoing Keynote-158 trial, a phase II basket study, is evaluating the safety and clinical activity of pembrolizumab in multiple tumor types, including patients with cervical cancer. Results from an interim analysis of a cohort of 98 patients with previously treated advanced cervical cancer who were treated with pembrolizumab monotherapy (200 mg intravenously every 3 weeks) were recently published in the Journal of Clinical Oncology.

At a median follow-up of 10.2 months, the objective response rate (ORR) among the entire trial population was 12.2%, including 3 complete responses. The majority of patients (82 of 98; 83.7%) had PD-L1-positive tumors (combined positive score of ³1), and for these patients the ORR was 14.6%. All but one of the responses occurred in patients who had been previously treated with one or more lines of chemotherapy, and the ORR in this population was 14.3%. The median duration of response was not reached. The majority (90.9%) of responses lasted at least six months, and 6 responses were ongoing at data cut-off.

The median progression-free survival (PFS) was 2.1 months, with an estimated 6-month PFS rate of 25.0%. There was no difference in PFS between PD-L1-positive and PD-L1-negative patients. However, the overall survival (OS) was longer in PD-L1-positive patients than PD-L1-negative patients (11 months vs 9.4 months). Similarly, the estimated 6-month OS rate was 80.2% in PD-L1-positive patients, compared to 75.2% in PD-L1-negative patients.

The adverse event (AE) profile was consistent with the known safety of pembrolizumab. A total of 65.3% of patients experienced a treatment-related AE, and grade 3/4 treatment-related AEs occurred in 12.2% of patients. The most common treatment-related AEs of any grade were hypothyroidism (10.2%), decreased appetite (9.2%), fatigue (9.2%), and diarrhea (8.2%). Only 4 patients (4.1%) discontinued treatment because treatment-related AEs, and there were no treatment-related deaths.

The investigators concluded that these results are clinically meaningful and support pembrolizumab as a therapeutic option for a subset of patients with previously treated advanced cervical cancer. Based on these results, pembrolizumab monotherapy has been granted accelerated approval in the United States for patients with PD-L1-positive advanced cervical cancer who have progressed on prior chemotherapy. Ongoing trials are currently investigating pembrolizumab in combination with other treatments, including combination with chemotherapy plus bevacizumab for patients with recurrent or metastatic cervical cancer and with concurrent or sequential chemoradation for locally advanced cervical cancer.

J Clin Oncol. 2019 April 3. [Epub ahead of print.]

Clinical Opinion Poll

When would you recommend dabrafenib + trametinib combo for a patient with advanced, symptomatic, PD-L1–low, lung adenocarcinoma and BRAF V600 mutation?