Nasopharyngeal cancer (NPC) is a rare disease in Western countries, while in Southeast Asia the incidence is high. Most patients are diagnosed at an advanced stage, which is usually treated with platinum-based chemotherapy, e.g. cisplatin-gemcitabine. However, despite treatment, the prognosis remains poor, revealing a persistent unmet need for more effective treatment options. Fortunately, the addition of immunotherapy to chemotherapy has recently showed promising efficacy in this disease space.

During the April ASCO Plenary Series, Dr Li Zhang (Sun Yat-sen University Cancer Center in Guangzhou, China) presented updated results from the randomized, double-blind, phase III RATIONALE-309 trial. The trial, which was conducted in China, evaluated the efficacy and safety of PD-1 inhibitor tislelizumab in combination with standard gemcitabine-cisplatin chemotherapy as first-line treatment for patients with advanced NPC. In total, 263 treatment-naïve patients with recurrent/metastatic (R/M) NPC were randomized to receive either tislelizumab or placebo, in combination with gemcitabine-cisplatin for up to 6 cycles, followed by maintenance tislelizumab monotherapy or placebo until disease progression or intolerable toxicity. At the interim analysis (median follow-up of 10 months), the primary endpoint was met with a median PFS of 9.2 months for tislelizumab plus chemotherapy compared with 7.4 months for placebo plus chemotherapy (hazard ratio [HR], 0.52; P < 0.0001), as assessed by independent review committee (IRC). The updated analysis at a median follow-up of 15.5 months, showed a consistent benefit in median PFS with tislelizumab plus chemotherapy (9.6 vs. 7.4 months; HR, 0.50). Despite a crossover rate of around 40% and immature overall survival (OS) data at the time of this analysis, tislelizumab plus chemotherapy indicated a favorable OS benefit (not reached [NR] vs. 23 months; HR, 0.60). Additionally, tislelizumab plus chemotherapy demonstrated a substantial improvement in median PFS2 (PFS after the subsequent line of therapy; NR vs. 13.9 months; HR, 0.38).

The benefit in PFS was seen regardless of PD-L1 expression; however, results of gene expression profiling indicated that patients with a ‘’hot’’ tumor microenvironment, characterized by a high expression of immune cells, may derive the greatest PFS benefit. The safety profile of tislelizumab plus chemotherapy was consistent with previous experience, with no new safety signals identified. Based on the results of this analysis, Dr Zhang concluded that tislelizumab plus chemotherapy may become a standard of care first-line therapy for patients with R/M NPC. In his excellent discussion of the study, Dr Robert Haddad, (Dana-Farber Cancer Institute, Boston, US) praised the RATIONALE-309 trial, noting that it is the third phase III trial to compare a PD-1 inhibitor plus chemotherapy with standard chemotherapy as first-line treatment of advanced NPC. Previously, the JUPITER-02 trial assessed toripalimab, while the CAPTAIN-1st trial evaluated camrelizumab. All three PD-1 inhibitors in these important trials resulted in robust improvements in PFS, with HRs ranging from 0.50 to 0.54. He also noted that, based on these results, the NCCN recently adapted its head and neck cancer guidelines to include gemcitabine-cisplatin plus a PD-1 inhibitor as one of the “Other Recommended Regimens” for the first-line treatment of advanced NPC. Although, as none of the three PD-1 inhibitors used in the NPC trials are available in the US, the NCCN currently recommends combination with either pembrolizumab or nivolumab.

Reference:
Zhang L, et al. J Clin Oncol. 2022;40 (no.36_suppl); Abstract 384950.