Tislelizumab outclasses docetaxel in previously treated advanced/metastatic NSCLC

Treatment with tislelizumab results in longer overall survival (OS), prolonged progression-free survival (PFS), higher objective response rates (ORRs), more durable responses, and fewer grade ≥3 treatment-emergent (TEAEs) and treatment-related adverse events (TRAEs) compared with docetaxel, according to the RATIONALE-303 study.

“After an additional 30 months of follow-up since the final analysis, patients with previously treated locally advanced or metastatic nonsmall cell lung cancer (NSCLC) continued to experience clinically meaningful and durable survival benefits with tislelizumab compared with docetaxel,” said study co-author Dr Kirsha Naicker, BeOne Medicines, Ltd, London, UK.

RATIONALE-303 was a phase III trial comparing tislelizumab with docetaxel in NSCLC patients who were previously treated with platinum-based chemotherapy. Naicker and her team estimated time-to-event endpoints using Kaplan–Meier methodology, with the Brookmeyer and Crowley method used to estimate 95 percent confidence intervals (CIs) for median PFS, OS, and duration of response (DoR).

The research team used the Cochran‒Mantel‒Haenszel chi-square test to calculate ORR differences and odds ratios between arms and Cox models (histology, prior lines of therapy, and PD-L1 tumour cell [TC] expression) to calculate the hazard ratios (HRs).

Of the 805 eligible patients, 535 (66.5 percent) were randomized to tislelizumab and 270 (33.5 percent) to docetaxel. Baseline characteristics were balanced between the two groups, with a median age of 61.0 years and predominantly male patients (77.8 percent tislelizumab; 76.3 percent docetaxel).

A total of 343 patients (42.6 percent) had PD-L1 TC expression ≥25 percent (42.4 percent tislelizumab; 43.0 percent docetaxel), while 13 patients were included in the intent-to-treat (ITT) population (one on tislelizumab and 12 on docetaxel). This analysis reported an additional 30 months of follow-up since the final analysis. [WCLC 2025, abstract P1.11.35]

Efficacy

“The OS benefit of tislelizumab compared with docetaxel was maintained relative to the final analysis in both the ITT population and the PD-L1 TC expression ≥25-percent subgroup,” Naicker said.

The median OS in the ITT population was 16.9 months with tislelizumab vs 11.9 months with docetaxel (HR, 0.67, 95 percent CI, 0.57‒0.79). In the PD-L1 TC expression ≥25-percent subgroup, the corresponding OS was 19.3 vs 11.5 months (HR, 0.52, 95 percent CI, 0.50‒0.68).

“In both populations, OS rates at 12, 24, 36, and 48 months were consistently higher in the tislelizumab arm compared with the docetaxel arm,” Naicker said.

The median PFS was also longer with tislelizumab than with docetaxel (4.2 vs 2.6 months; HR, 0.64, 95 percent CI, 0.54‒0.76) in the ITT population. Similarly, PFS rates were higher with tislelizumab at 12, 14, and 36 months.

Other relevant outcomes, such as ORR (22.6 percent vs 7.8 percent), DCR (55.7 percent vs 42.2 percent), and DoR (13.5 vs 6.1 months), were also significantly higher in the tislelizumab arm than the docetaxel arm in both the ITT population and the PD-L1 TC expression ≥25-percent subgroup.

Safety profile

Patients treated with tislelizumab had a lower rate of grade ≥3 TEAEs than those treated with docetaxel (43.6 percent vs 74.8 percent) despite having a longer treatment duration (~5.5 vs ~2.1 months).

Likewise, the incidence of any-grade, grade ≥3, and serious TRAEs (75.7 percent vs 93.8 percent) and discontinuations (7.1 percent vs 10.1 percent) due to TRAEs was lower in the tislelizumab group than the docetaxel group.

“Our findings continue to demonstrate tislelizumab as a treatment option for previously treated patients with locally advanced or metastatic NSCLC,” Naicker said.