Clinical study results indicate pembrolizumab monotherapy improves response rate in patients with advanced refractory esophageal cancer.
Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide, with a median overall survival (OS) rate of <12 months for patients with advanced disease. Immune checkpoint inhibitors have demonstrated some efficacy in patients with advanced esophageal cancer, including pembrolizumab, a monoclonal antibody that binds to T-cell PD-1 receptors to inhibit T-cell proliferation. Pembrolizumab monotherapy use in adult patients with advanced chemotherapy-refractory esophageal cancer who had ≥1 prior therapies was studied in an open-label, multicenter phase 2 clinical trial. The study participants had confirmed unresectable or metastatic esophageal squamous-cell carcinoma (SCC) or esophageal or gastroesophageal junction adenocarcinoma. There were 49 patients in the trial; 39 were diagnosed with adenocarcinoma and 10 were diagnosed with esophageal SCC. Most patients had ≥3 lines of systemic therapy before enrollment in the trial. Patient tumor samples and blood samples were evaluated for tumor mutational burden, PD-L1 expression, immune commixture, mononuclear cells, and chemokines.
Treatment consisted of 200 mg pembrolizumab intravenously every 3 weeks, which was continued until cancer progressed, the patient experienced unacceptable adverse events (AEs), or the patient withdrew consent for treatment. All patients received ≥1 treatment cycles during the study period. To assess response, tumor imaging was performed prior to treatment and then every 9 weeks. The study primary end point was overall response rate (ORR), determined by a complete or partial response to therapy. Secondary end points were OS, progression-free survival (PFS), duration of response, safety, and tolerability. PD-L1 status was determined in the analysis but was not a criterion for study eligibility.
The ORR was 8% (4/49 patients) and the median OS was 5.8 months. Median OS in patients with adenocarcinoma was 4.8 months and median PFS was 1.8 months. Analysis of PD-L1–positive patients found the ORR for this patient subgroup was 13.3% and median OS was 7.9 months. Tumor mutational burden was estimated for 27 patients. Tumor mutational status ≥10 mutations/megabase was found in 7 patients who also demonstrated a trend toward improved OS. Partial response occurred in 8% of patients, stable disease in 22%, and 67% had progressive disease, with 6 patients having rapid clinical progression. Cytokine/chemokine analysis determined that baseline CXCL10 had a favorable association with survival, whereas interleukin-2 receptor α and interleukin-6 had an unfavorable association with survival.
Treatment-related AEs occurred in 38 patients. Fatigue, dyspnea, rash, anorexia, arthralgia, and pruritus were the most common AEs. Grade 3 to 4 treatment-related AEs occurred in 6 patients and 3 discontinued treatment due to treatment-related AEs.
Pembrolizumab monotherapy demonstrated a modest response for patients with refractory esophageal cancer.
Source: de Klerk LK, Patel AK, Derks S, et al. Phase 2 study of pembrolizumab in refractory esophageal cancer with correlates of response and survival. J Immunother Cancer. 2021;9:e002472.