Frontline tislelizumab plus chemo shows sustained survival advantage in NPC

In the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC), the combination of tislelizumab plus chemotherapy confers sustained survival benefit, according to 3-year data from the RATIONALE-309 trial.

RATIONALE-309 included 263 treatment-naïve adults (median age 50 years, 78.3 percent male) with histologically or cytologically confirmed recurrent or metastatic NPC. These participants were randomly assigned to receive tislelizumab 200 mg (n=131) or placebo (n=132) intravenously every 3 weeks, both in combination with gemcitabine and cisplatin for 4 to 6 cycles. Participants in the placebo arm could cross over to tislelizumab monotherapy upon disease progression.

Progression-free survival (PFS), the primary endpoint, was assessed by an independent review committee. Secondary endpoints included overall survival (OS), PFS after next-line therapy, and safety.

The median PFS was 9.6 months in the tislelizumab arm vs 7.4 months in the placebo arm. The addition of tislelizumab to chemotherapy was associated with a 47-percent reduction in the risk of progression or death (hazard ratio [HR], 0.53, 95 percent CI, 0.39–0.71).

Similarly, the median OS was higher in the tislelizumab vs the placebo arm, at 45.3 vs 31.8 months (HR, 0.73, 95 percent CI, 0.51–1.05). Tislelizumab plus chemotherapy was associated with greater OS benefit than chemotherapy alone both in rank-preserving structural failure time analysis (HR, 0.56, 95 percent CI, 0.27–1.19) and two-stage crossover-adjusted analysis (HR, 0.62, 95 percent CI, 0.40–0.97).

In terms of safety, treatment-emergent adverse events (AEs) occurred in 100 percent of participants in the tislelizumab arm and 99.2 percent in the placebo arm. The frequency of grade 3 or higher AEs were similar between the two arms.

More participants in the tislelizumab arm than in the placebo arm had immune-mediated AEs (53.4 percent vs 37.7 percent), although these events were mostly of grades 1 or 2.

Notably, high B-cell gene expression was associated with greater OS benefit (HR, 0.41, 95 percent CI, 0.23–0.74).