Pembrolizumab/Bevacizumab Improves Efficacy in Nasopharyngeal Carcinoma

Pembrolizumab and bevacizumab yielded an ORR of 58.3% vs 12.5% with pembrolizumab monotherapy in patients with platinum-resistant nasopharyngeal carcinoma.

Data from a randomized, open-label phase 2 trial (NCT03813394) showed that pembrolizumab (Keytruda) in combination with bevacizumab (Avastin) elicited favorable clinical efficacy compared with pembrolizumab monotherapy in patients with platinum-resistant nasopharyngeal carcinoma, according to a study published in Lancet Oncology.

At a medium follow-up of 28.3 months (IQR, 15.1-55.9), the objective response rate (ORR) was 58.3% (95% CI, 36.6%-77.9%) with 1 complete response (CR) and 13 partial responses (PRs) in the pembrolizumab and bevacizumab arm vs 12.5% (95% CI, 2.7%-32.4%) with 1 CR and 2 PRs in the pembrolizumab arm (unadjusted risk ratio, 4.67; 95% CI, 1.54-14.18; P = .0010).

The median progression-free survival (PFS) was 13.8 months (95% CI, 4.2-29.5) in the combination arm compared with 1.6 months (95% CI, 1.3-2.7) in the monotherapy arm (HR, 0.25; 95% CI, 0.13-0.50; P <.0001). In the combination arm, progression or death occurred in 79% with 14 patients progressing and 5 patients dying, and 100% of patients with all 24 patients experiencing progression in the monotherapy arm. Median overall survival (OS) was 18.5 months (95% CI, 9.1-not reached [NR]) vs 11.7 months (95% CI, 7.0-16.1); 54% and 67% of patients in each respective group died.

A post-hoc analysis showed the median duration of response to be 16.4 months (95% CI, 11.7-29.5) in the combination arm and 8.8 months (95% CI, 7.1-22.6) in the monotherapy arm.

“To our knowledge, this is the first randomized study in recurrent or metastatic nasopharyngeal carcinoma comparing anti–PD-1 therapy with or without anti-VEGF treatment,” senior study author Boon-Cher Goh, professor in the Department of Pharmacology and Department of Medicine at National University of Singapore, and senior consultant in the Department of Hematology-Oncology and deputy director of the National University Cancer Center, Singapore, wrote in the paper with coauthors. “[T]his trial confirms the effectiveness of bevacizumab and pembrolizumab as a chemotherapy-free regimen for recurrent or metastatic nasopharyngeal carcinoma and warrants further evaluation against the standard of care.”

A total of 48 patients were randomly assigned, in a 1:1 ratio, to receive either 200 mg of intravenous pembrolizumab and 7.5 mg/kg of intravenous bevacizumab administered 1 week before pembrolizumab (n = 24) or 200 mg of pembrolizumab monotherapy (n = 24).

Eligible candidates were 21 years or older with recurrent or metastatic histologically confirmed Epstein-Barr encoding region–in situ hybridization-positive nasopharyngeal carcinoma who have received at least 1 prior line of platinum-based chemotherapy and exhibited tumor progression after previous treatment. Additional criteria included an ECOG performance status of 0 or 1; adequate bone marrow, renal, and hepatic functions; evaluable disease per RECIST v1.1 guidelines; and tumors amenable for repeat biopsy either by core needles or punch biopsy with forceps.

Disease amenable to curative radiotherapy or surgery; uncontrolled hypertension; active coronary artery disease; clinically significant bleeding in the past 30 days; previous treatment with an anti–PD-1, anti–PD-L1, or anti–CTLA4 antibody; active autoimmune disease requiring systemic steroid therapy; any form of immunosuppressive therapy within 14 days of first trial dose; and New York Heart Association congestive heart failure are among criteria that prevented patients from being eligible.

The primary trial end point was ORR. Key secondary end points were PFS and safety.

Regarding safety, treatment-related adverse events (TRAEs) of any grade occurred in 83% of patients in the combination arm and 50% of patients in the monotherapy arm. The most common TRAEs were fatigue (25% vs 21%), dermatological toxicities (33% vs 21%), and arthralgia or arthritis (8% vs 17%). AEs of grade 3 occurred in 29% and 8% of patients.

Treatment was delayed in 50% and 33% of patients, respectively. In the combination group, 6 patients discontinued bevacizumab, including 4 due to grade 3 TRAEs, and 13% discontinued pembrolizumab and bevacizumab due to severe TRAEs including colitis, bullous pemphigoid, and cerebrovascular thrombosis. In the monotherapy group, 0 patients discontinued pembrolizumab due to toxicities.

Reference

Chong WQ, Low JL, Tay JK, et al. Pembrolizumab with or without bevacizumab in platinum-resistant recurrent or metastatic nasopharyngeal carcinoma: a randomised, open-label, phase 2 trial. Lancet Oncol. 2025;26(2):175-186. doi:10.1016/S1470-2045(24)00677-6