Tislelizumab add-on to chemo sustains PFS in nasopharyngeal cancer

Adding tislelizumab to chemotherapy in the first-line setting sustains progression-free survival (PFS) benefit in patients with recurrent/metastatic nasopharyngeal cancer (R/M NPC), according to updated results of the RATIONALE-309* trial presented at the ASCO Plenary 2022.

This phase III, double-blind trial involved 263 patients with R/M NPC who were randomly assigned to receive either intravenous tislelizumab 200 mg (n=131) or placebo (n=132) on day 1 Q3W in addition to standard chemotherapy (gemcitabine 1 g/m² on days 1 and 8 plus cisplatin 80 mg/m² on day 1 Q3W for up to 4–6 cycles). Patients continued treatment until disease progression, intolerable toxicity, death, or withdrawal of consent. A total of 65 placebo recipients were crossed over to receive tislelizumab monotherapy after IRC**-confirmed disease progression. [ASCO Plenary 2022, abstract 384950]

At an extended median follow-up of 15.5 months, PFS, as assessed by IRC, was greater in the tislelizumab + chemo arm compared with the placebo + chemo arm (median 9.6 vs 7.4 months; stratified hazard ratio [HR], 0.50).

The median overall survival (OS) was not reached in the tislelizumab + chemo arm and was 23.0 months in the placebo arm (stratified HR, 0.60). However, final OS data are still immature, noted lead investigator Dr Li Zhang from the Sun Yat-sen University Cancer Centre in Guangzhou, China. 

Patients treated with tislelizumab + chemo also demonstrated a substantial improvement in PFS after next line of treatment (PFS2) than those treated with placebo + chemo (median PFS2 not reached vs 13.9 months; unstratified HR, 0.38).

“This result indicates that tislelizumab + chemo should be used in the first line to deliver the maximum clinical benefit,” Zhang noted.

Gene expression profiling, which identified three gene expression clusters as potential biomarkers for efficacy (ie, ‘cold’, ‘medium’, and ‘hot’ tumour microenvironment), showed that patients with a ‘hot’ tumour immune profile achieved a greater PFS benefit with tislelizumab + chemo vs those with ‘medium’ or ‘cold’ tumours.

In addition, a high level of activated dendritic cell (DC) signature was associated with an enhanced PFS benefit with tislelizumab + chemo compared with a low level of DC signature. “This result advocates the use of a DC signature as a potential biomarker tool. [However,] further research is warranted,” said Zhang.

Leukopenia, neutropenia, anaemia, and thrombocytopenia were the most commonly reported adverse events for both treatment arms. Tislelizumab + chemo showed a manageable safety profile with no new safety signals observed.

“[Overall, the results] showed that PFS remained consistent with the interim analysis and demonstrated a clinically meaningful improvement for tislelizumab + chemo vs placebo + chemo,” said Zhang.

“These findings [also] support the use of tislelizumab in combination with chemotherapy as a potential standard-of-care as first-line therapy in R/M NPC,” he added. 

*RATIONALE-309: Tislelizumab combined with chemotherapy versus chemotherapy alone in recurrent or metastatic nasopharyngeal cancer