A phase II clinical trial conducted in Singapore has revealed promising results for patients with platinum-resistant recurrent or metastatic nasopharyngeal carcinoma, showing significant benefits from combining bevacizumab with pembrolizumab immunotherapy.
The randomized, open-label study enrolled 48 patients across two Singaporean sites between May 2019 and December 2023. Patients received either pembrolizumab (200 mg every 21 days) plus bevacizumab (7.5 mg/kg one week before each pembrolizumab dose) or pembrolizumab alone, continuing treatment until disease progression, unacceptable toxicity, or completion of 32 cycles.
Significant Improvement in Response Rates
The combination therapy demonstrated remarkable efficacy, achieving an objective response rate of 58.3% (95% CI: 36.6%-77.9%) compared to 12.5% (95% CI: 2.7%-32.4%) with pembrolizumab monotherapy. This represents a relative risk of 4.67 (95% CI: 1.54-14.18, P = .0010). Complete responses were observed in one patient from each treatment arm, with an additional 25% and 21% of patients achieving stable disease in the combination and monotherapy arms, respectively.
Enhanced Survival Outcomes
The durability of response proved superior with the combination approach. Median response duration reached 16.4 months (95% CI: 11.7-29.5 months) for bevacizumab plus pembrolizumab, compared to 8.8 months (95% CI: 7.1-22.6 months) for pembrolizumab alone. More strikingly, median progression-free survival showed a dramatic improvement: 13.8 months (95% CI: 4.2-29.5 months) with the combination versus 1.6 months (95% CI: 1.3-2.7 months) with monotherapy (HR = 0.25, 95% CI: 0.13-0.50, P < .0001).
Safety and Tolerability Profile
The safety profile, while showing increased adverse events with the combination therapy, remained within manageable limits. Grade 3 treatment-related adverse events occurred in 29% of patients receiving the combination therapy compared to 8% in the monotherapy group. The most common significant adverse event in the combination arm was thrombosis/bleeding, affecting 17% of patients. Importantly, no grade 4 or 5 treatment-related adverse events were reported in either group.
Clinical Implications
"Pembrolizumab in combination with bevacizumab was more efficacious than pembrolizumab monotherapy, with manageable toxicities in platinum-resistant nasopharyngeal carcinoma," stated the research team led by Dr. Boon-Cher Goh from the Cancer Science Institute of Singapore, National University of Singapore. They emphasized that if these results are validated in a phase III trial, this combination therapy could establish a new standard of care for this patient population.
With median follow-up reaching 28.3 months (interquartile range: 15.1-55.9 months), these findings represent a significant step forward in addressing the therapeutic challenges faced by patients with platinum-resistant nasopharyngeal carcinoma, a condition with historically limited treatment options.
