Pembrolizumab safe and effective for heavily pretreated advanced oesophageal cancer
Pembrolizumab has demonstrated durable antitumour activity with manageable safety in patients with heavily pretreated oesophageal cancer in the phase II KEYNOTE-180 study.
The open-label, multicentre, international study conducted from January 2016 to March 2017 included 121 patients (83 percent male; median age, 65 years) with advanced, metastatic oesophageal cancer (oesophageal squamous cell carcinoma [ESCC], 52.1 percent; adenocarcinoma, 47.9 percent) that progressed after two or more lines of therapy. [JAMA Oncol 2018, doi: 10.1001/jamaoncol.2018.5441]
Results from the study showed that the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST, version 1.1) was 9.9 percent (95 percent confidence interval [CI], 5.2 to 16.7 percent) among all patients.
The ORR was higher among patients positive for programmed death ligand-1 (PD-L1) vs those who were PD-L1 negative (13.8 percent [95 percent CI, 6.1 to 25.4 percent] vs 6.3 percent [95 percent CI, 1.8 to 15.5 percent]), and also higher among patients with ESCC vs adenocarcinoma (14.3 percent [95 percent CI, 6.7 to 25.4 percent] vs 5.2 percent [95 percent CI, 1.1 to 14.4 percent]).
“After a median follow-up period of 13.3 months among responders, the median duration of response was not reached [ESCC range, 1.9−14.4 months; adenocarcinoma range, 2.1−5.4 months], suggesting durability of the response,” the authors of the study commented.
“Survival outcomes were also encouraging, with a median overall survival [OS] of 5.8 months [95 percent CI, 4.5 to 7.2 months]. The 6-month and 12-month OS rates were 49 percent [95 percent CI, 40 to 57 percent] and 28 percent [95 percent CI, 20 to 37 percent], respectively,” they added.
Median OS was also shown to be higher among patients with ESCC vs adenocarcinoma (6.8 months [95 percent CI, 5.4 to 8.9 months] vs 3.9 months [95 percent CI, 3.2 to 6.3 months]).
Median overall progression-free survival (PFS) was 2 months (95 percent CI, 1.9 to 2.1 months), with a 6-month PFS rate of 16 percent (95 percent CI, 10 to 23 percent) and a 9-month PFS rate of 9 percent (95 percent CI, 5 to 16 percent).
Treatment-related adverse effects (AEs) were experienced by 57.9 percent of the patients. The most common AEs reported were fatigue (10.7 percent), rash (7.4 percent), pruritus (6.6 percent), hypothyroidism (5.8 percent) and diarrhoea (5 percent).
Immune-mediated AEs occurred in 20.7 percent of patients and included hypothyroidism (7.4 percent) and pneumonitis (7.4 percent).
In the study, pembrolizumab 200 mg was administered intravenously every 3 weeks until disease progression, unacceptable toxic effects or study withdrawal for up to 2 years.
Phase III studies are ongoing to evaluate pembrolizumab vs standard therapy for patients with oesophageal cancer progressing after first-line therapy or pembrolizumab in combination with chemotherapy as first-line therapy for patients with locally advanced, unresectable or metastatic oesophageal cancer.
Pembrolizumab is a high-affinity, humanized monoclonal antibody against programmed cell death protein 1 (PD-1) that blocks interaction between PD-1 and PD-L1 or programmed death-ligand 2. [N Engl J Med 2013;369:134-144] The phase Ib KEYNOTE-028 study demonstrated durable responses to pembrolizumab in patients with PD-L1–positive advanced and metastatic oesophageal cancer. [Clin Oncol 2018;36:61-67]