Pembrolizumab Shows Response in Metastatic Nasopharyngeal Carcinoma

Over a fifth of patients with previously treated advanced nasopharyngeal carcinoma showed a measureable response, when treated with pembrolizumab, an immune checkpoint inhibitor.

Chiun Hsu, MD

Chiun Hsu, MD

Over a fifth of patients with previously treated advanced nasopharyngeal carcinoma showed a measurable response, when treated with pembrolizumab, an immune checkpoint inhibitor, according to a study that was reported at this year’s European Cancer Congress.

Two-thirds of patients in the study had some degree of reduction in target lesion size. The median duration of response was 10.8 months. The objective response rate with pembrolizumab in nasopharyngeal carcinoma was 22.2%, which consisted of all partial responses. Another 15 patients had stable disease, resulting in a disease control rate of 77.8%.

“This is the first demonstration of robust clinical activity of a PD-1 inhibitor in patients with recurrent metastatic nasopharyngeal carcinoma,” said lead investigator Chiun Hsu, MD, a head and neck cancer specialist at National Taiwan University Hospital in Taipei. “Pembrolizumab showed a manageable safety profile, and further investigation of advanced nasopharyngeal carcinoma is planned.”

Nasopharyngeal carcinoma is uncommon in the United States and Europe, but it is a major cancer problem in certain parts of Asia. For example, Southern China has an incidence of 26.9 cases per 100,000, compared with less than 1/100,000 in the United States and 0.1-2.2/100,000 in Europe.

Options for frontline curative therapy consist of radiation therapy for patients with stage I disease and chemoradiation for stages IIa to IVa/b. Patients who have recurrent or metastatic disease have limited options, consisting primarily of palliative chemotherapy, mostly with platinum-based combinations. Patients with advanced nasopharyngeal carcinoma have a median survival of 5 to 11 months, Hsu said.

Elevated PD-L1 expression is common in cancers associated with Epstein-Barr virus (EBV) infection, such as nasopharyngeal carcinoma. PD-L1 expression in nasopharyngeal carcinoma is upregulated by EBV-induced activation of the LMP1 and interferon-gamma pathways, Hsu continued. As such, PD-1 and PD-L1 expression might correlate with poor prognosis in patients with nasopharyngeal carcinoma.

Investigators evaluated pembrolizumab activity in a phase Ib multi-cohort study involving patients with PD-L1 positive advanced solid tumors, which includes 44 patients with recurrent or metastatic nasopharyngeal carcinoma. All but three of the patients tested positive for PD-L1 expression.

Subsequently, 27 patients with advanced nasopharyngeal carcinoma were enrolled in the trial. The patients received pembrolizumab 10 mg/kg IV every 2 weeks. Patients who achieved complete or partial response continued at the same dose until disease progression or development of intolerable toxicity. Patients with confirmed disease progression discontinued pembrolizumab.

All but 2 of the patients had received at least 1 prior line of therapy for advanced disease, and a third of the patients had received 5 or more prior regimens.

The cohort had a median follow-up of 12.9 months and a median time to response of 1.8 months. In patients with stable disease, the median duration was 5.6 months. Median progression-free survival (PFS) was 5.6 months. PFS was 49.7% at 6 months and 28.9% at 12 months.

The most frequent all-grade adverse events (AEs) with pembrolizumab were pruritus (25.9%), fatigue (18.5%), hypothyroidism (18.5%), hepatitis (11.1%), hepatitis (11.1%), herpes zoster (11.1%), pneumonitis (11.1%), rash (11.1%), and maculo-papular rash (11.1%). The most common grade 3-5 AEs were hepatitis (7.4%) and pneumonitis (7.4%). There was one treatment-associated death related to bacterial sepsis.

“Advanced nasopharyngeal carcinoma is a severe form of head and neck cancer often associated with a poor prognosis,” Hsu said in a statement. “These data presented at ECC represent the potential for new approaches to treat this type of cancer, for which there are currently limited treatment options, and further support the need for additional research into how Keytruda may work for certain types of head and neck cancer.”

Approved in the United States and Europe for use in treatment-refractory metastatic melanoma, pembrolizumab has been evaluated as monotherapy and in combinations for more than 30 different types of tumors, Hsu noted. The drug has demonstrated substantial antitumor activity in multiple cancers.

Hsu C, Lee S, Ejadi S, et al. Antitumor activity and safety of pembrolizumab in patients with PD-L1-positive nasopharyngeal carcinoma: Interim results from a phase 1b study. Presented at: 2015 European Cancer Congress; September 25-29; Vienna, Austria. Abstract 2801.

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