PD-1 Inhibitor Boosts PFS in Metastatic Nasopharyngeal Carcinoma

The addition of the investigational PD-1 inhibitor camrelizumab to first-line therapy significantly improved progression-free survival (PFS) in patients with recurrent or metastatic nasopharyngeal carcinoma, a phase III trial found.

Over a median follow-up of 15.6 months, patients treated with camrelizumab plus gemcitabine and cisplatin achieved a median PFS, the primary endpoint, of 10.8 months, compared with 6.9 months for patients who received the chemotherapy regimen plus placebo (HR 0.51, 95% CI 0.37-0.69, P<0.0001), reported Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China.

“These data suggest that first-line treatment with camrelizumab plus gemcitabine/cisplatin could be a standard of care for refractory/metastatic nasopharyngeal carcinoma,” Zhang said in an oral presentation at the virtual American Society of Clinical Oncology (ASCO) annual meeting.

Of note, there was no difference in objective response rate (ORR), which was 88% for patients on camrelizumab, with seven patients achieving a complete response, compared with 80% for patients on placebo (P=0.1063).

“Metastatic nasopharyngeal carcinoma is one of the most aggressive head and neck cancers that frequently metastasizes to distant organs. The current first-line standard of care is gemcitabine/cisplatin, which is associated with a response rate of 64%, but the median progression-free survival is only about 7 months,” commented ASCO discussant Nicole Chau, MD, of the University of British Columbia/BC Cancer Agency in Vancouver.

“No standard second-line therapy exists,” she added. “In phase I trials, treatment with camrelizumab plus chemotherapy exhibited a 91% response rate. Dr. Zhang and colleagues built upon this finding. They should be congratulated for being the first to complete a randomized phase III trial evaluating a PD-1 inhibitor with gemcitabine/cisplatin in metastatic nasopharyngeal cancer.”

She suggested that the positive finding of a longer PFS was encouraging. There were similar findings for investigator-assessed PFS. While there was no difference in ORR between the two groups, Chau noted there was a difference in duration of response — 9.9 months on camrelizumab and 5.7 months on chemotherapy alone (P<0.0001). She said that overall survival (OS) data were immature, although there was a trend in favor of patients treated with camrelizumab.

Study Details

From November 2018 to November 2019, Zhang and colleagues enrolled 263 patients from 28 centers; 134 patients were randomized to receive camrelizumab plus gemcitabine and cisplatin and 129 patients were randomized to placebo and the chemotherapy regimen. More than two-thirds of patients in both study arms were able to complete 6 cycles of therapy.

Patients were eligible for the study if they were age 75 or younger, had pathologically confirmed recurrent or metastatic nasopharyngeal carcinoma, had not received systemic therapy for the metastatic disease, had good performance status, and had tumors that could be measured by RECIST criteria.

Patients were treated with camrelizumab 200 mg on the first day of a 21-day cycle, gemcitabine 1,000 mg/m² on days 1 and 8, and cisplatin 80 mg/m² on day 1. They were maintained on that regimen for 4 to 6 cycles. The placebo patients received the same chemotherapy regimen.

The primary endpoint was PFS per independent review committee. Secondary endpoints included investigator-assessed PFS, ORR, duration of response, OS, and tolerability.

Zhang said that adverse events with both regimens were common and similar; however, the safety profile was as expected, with no new signals observed. Grade 3 or higher treatment-related adverse events occurred in 93% of patients in the camrelizumab arm and 90% in the placebo arm.

The most common treatment-related adverse events were decreased white blood cell count, decreased neutrophil count, decreased platelet count, and anemia.

Chau suggested that the study’s results raise questions about whether treatment of metastatic nasopharyngeal carcinoma can be personalized if researchers explore levels of PD-L1 expression, tumor mutation burden, Epstein-Barr virus DNA, and other genetic aberrations.

“It will be important to see if this study’s findings can be confirmed in a more diverse population of patients,” said Chau.