Pembrolizumab (Keytruda) induced an overall response rate of 25.9% and was well tolerated in patients with PD-L1–positive recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), according to findings from the KEYNOTE-028 study published online in the Journal of Clinical Oncology
The international, nonrandomized, multi-arm, phase Ib KEYNOTE-028 trial (NCT02054806) explored the safety and activity of pembrolizumab in patients with advanced solid tumors. Key eligibility criteria for the NPC cohort included unresectable or metastatic disease, failure on prior standard therapy, and PD-L1 expression in 1% or more of tumor cells or tumor-infiltrating lymphocytes.
Forty-one patients with NPC in Canada, France, Italy, Japan, South Korea, the Netherlands, Spain, the Republic of China (Taiwan), the United Kingdom, and the United States were found to have PD-L1–positive tumors. Fourteen did not meet inclusion criteria and 27 were treated with pembrolizumab. The reasons for exclusion included no informed consent (n = 4); inadequate organ function (n = 4); no measurable disease (n = 3); ECOG PS ineligible (n = 2); and previously received anti–PD-1, anti–PD-L1, and/or anti–PD-L2 therapy (n = 1).
All 27 treated patients had received prior therapy, most (92.6%) for recurrent or metastatic disease. Nineteen patients (70.4%) had received at least 3 prior lines of therapy for advanced disease. The most common prior therapies were cisplatin (92.6%) and fluorouracil (81.5%). Metastases in bone were the most common site (59.3%), followed by liver and lung (both 51.9%), and the lymph nodes (48.1%).
NPC is more common in Southeast Asia, the predominant histologic subtypes are nonkeratinizing differentiated or undifferentiated carcinoma (WHO classes II and III), with a crude incidence of 4.3 per 100,000 persons per year compared with a crude incidence of <1% in the West. Accordingly, 63% of the cohort was Asian.
Patients were assigned to 10 mg/kg IV of pembrolizumab once every 2 weeks for 24 months, or until confirmed progressive disease, unacceptable adverse events (AEs), patient refusal, or investigator decision. Three patients had completed the 2-year pembrolizumab treatment and 2 remained on study at the June 20, 2016, cutoff. Twenty-two patients discontinued for several reasons, including progressive disease (13), AEs (5), physician decision (2), and patient withdrawal (2).
The 25.9% investigator-assessed ORR, comprised 7 partial responses; no complete responses were observed. Fourteen patients (51.9%) experienced stable disease and 6 patients (22.2%) had progressive disease as their best response. One additional patient experienced an unconfirmed partial response.
A central review of 19 cases identified 5 partial responses and no complete responses for an ORR of 26.3%.
Eighteen of 27 patients (66.7%) experienced decreases in target lesion size. These reductions were durable in the 7 patients with a partial response, with a median duration of 17.0 months (range, 4.8 to ≥22.1). After a median follow-up of 20 months (range, 2.2 to 26.8), median time to response was 1.9 months (range, 1.4 to 16.4), median duration of response was 17.1 months (range, 4.8 to ≥22.1), and duration of stable disease was 5.6 months (range, ≥1.7 to ≥12.9+).
All patients experienced at least 1 AE, and 55.6% experienced at least 1 grade ≥3 AE. Twenty patients (74.1%) experienced drug-related AEs, most commonly rash (25.9%), pruritus (25.9%), pain (22.2%), fatigue (18.5%), and hypothyroidism (18.5%). Eight patients (29.6%) experienced grade ≥3 treatment-related AEs, including grade 3 pneumonitis, proteinuria, anemia, hepatitis, and facial pain. Investigators noted 1 instance of grade 4 hepatitis and increased blood creatine phosphokinase level, and 1 instance of grade 5 sepsis.
NPC is annually responsible for about 50,000 deaths worldwide. Standard-of-care treatment for recurrent or metastatic disease consists of platinum-containing multiagent chemotherapy, but there are no standard treatment options beyond the first-line setting for patients with platinum-refractory RM-NPC. Furthermore, despite numerous clinical trials, development of new systemic therapies for RM-NPC has stagnated over the past 20 years.
Hsu C, Lee S, Ejadi S, et al. Safety and antitumor activity of pembrolizumab in patients with programmed death-ligand 1–positive nasopharyngeal carcinoma: Results of the KEYNOTE-028 study [published online August 24, 2017]. J Clin Oncol. doi: 10.1200/JCO.2017.73.3675.