Adding tislelizumab to chemotherapy can improve outcomes in patients with recurrent or metastatic nasopharyngeal cancer (NPC), according to an updated analysis of the phase 3 RATIONALE-309 study.

Tislelizumab plus chemotherapy significantly improved both progression-free survival (PFS) and second PFS (PFS2), when compared with chemotherapy alone. 

Patients derived a benefit from tislelizumab regardless of PD-L1 expression, but researchers found that an activated dendritic cell (DC) signature may predict benefit.

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These findings were presented as an ASCO Plenary Series presentation by Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China.

The RATIONALE-309 trial ( Identifier: NCT03924986) enrolled 263 patients with recurrent or metastatic NPC. Patients were randomly assigned to receive tislelizumab (n=131) or placebo (n=132), each in combination with chemotherapy.

For chemotherapy, all patients received cisplatin (80 mg/m2 on day 1) and gemcitabine (1 g/m2 on days 1 and 8) every 3 weeks for 4-6 cycles. Patients also received tislelizumab (200 mg on day 1) or placebo every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or death. Patients in the placebo arm were allowed to cross over to the tislelizumab arm after disease progression.

At a median follow-up of 15.5 months, the median PFS was significantly longer in the tislelizumab arm than in the placebo arm — 9.6 months and 7.4 months, respectively (hazard ratio [HR], 0.50; 95% CI, 0.37-0.68). 

Tislelizumab also significantly improved PFS2. The median PFS2 was not reached in the tislelizumab arm and was 13.9 months in the placebo arm (HR, 0.38; 95% CI, 0.25-0.58).

Although the final overall survival (OS) data are not mature, there was a numeric OS benefit in the tislelizumab arm. The median OS was not reached in the tislelizumab arm and was 23.0 months in the placebo arm (HR, 0.60; 95% CI, 0.35-1.01).

In an exploratory analysis, researchers identified 3 gene expression clusters — “cold,” “medium,” and “hot” — as potential biomarkers for efficacy. 

A greater PFS benefit was observed with tislelizumab in patients with a hot tumor microenvironment, which was characterized by the highest expression of DCs, T cells, natural killer cells, and major histocompatibility complex and interferon-gamma signatures.

Dr Zhang noted that the greatest PFS benefit with tislelizumab was seen in patients with an activated DC signature. He said this supports the use of a DC signature as a potential biomarker for predicting efficacy.

Dr Zhang added that the safety profile of tislelizumab plus chemotherapy was consistent with previous reports. The most common grade 3 or higher adverse events in both treatment arms were hematologic toxicities. 

Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 80.9% of patients in the tislelizumab arm and 81.8% of those in the placebo arm. There were 5 fatal TEAEs in the tislelizumab arm and 2 fatal TEAEs in the placebo arm.

“The current data analysis indicated that tislelizumab plus chemotherapy may become a standard of care first-line therapy for patients with recurrent or metastatic nasopharyngeal carcinoma,” Dr Zhang concluded.

Disclosures: This research is supported by BeiGene, Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Zhang L, Yang Y, Pan J, et al. RATIONALE-309: Updated progression-free survival (PFS), PFS after next line of treatment (PFS2), and overall survival (OS) from a phase 3 double-blind trial of tislelizumab versus placebo, plus chemotherapy, as first-line treatment for recurrent/metastatic nasopharyngeal cancer (RM NPC). ASCO Plenary Series; April 19, 2022. Abstract 384950.