First-line tislelizumab plus chemo shows benefit in nsq-NSCLC with high PD-L1 expression

First-line treatment with tislelizumab plus chemotherapy showed better survival outcomes and response among patients with locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC), particularly those with high PD-L1 expression, compared with chemotherapy alone, according to a subgroup analysis of the phase III RATIONALE-304 trial presented at ELCC 2025.

This subgroup analysis included 110 patients (median age 62 years, 71.8 percent male) with advanced or metastatic nsq-NSCLC who had PD-L1 expression of ≥50 percent and were not amenable to curative surgery or radiotherapy.

Participants were randomized in a 2:1 ratio to receive intravenous tislelizumab 200 mg Q3W for 4–6 cycles plus platinum-based chemotherapy Q3W, followed by maintenance tislelizumab plus pemetrexed (tislelizumab plus chemotherapy arm; n=74) or platinum-based chemotherapy and pemetrexed Q3W, followed by maintenance pemetrexed (chemotherapy alone arm; n=36).

At a median follow-up of 16.5 months, patients who received tislelizumab plus chemotherapy had a longer median progression-free survival (PFS), as assessed by an independent review committee (ICR), than those who received chemotherapy alone (14.6 vs 4.6 months; stratified hazard ratio [HR], 0.31). [ELCC 2025, abstract P37P]

The PFS benefit of tislelizumab plus chemotherapy vs chemotherapy alone was also observed across all subgroups, noted the researchers.

The ICR-assessed objective response rate (ORR) was higher in the tislelizumab plus chemotherapy arm than the chemotherapy alone arm (70.3 percent vs 30.6 percent), as was the complete response (9.5 percent vs 0 percent).

Moreover, the median duration of response (DoR) was not estimable with tislelizumab plus chemotherapy vs 8.5 months with chemotherapy alone.

There was also a trend toward improved overall survival (OS) among patients on tislelizumab plus chemotherapy vs those on chemotherapy only (median OS, not estimable vs 13.1 months; HR, 0.39).

In an updated analysis, with an additional follow-up of 6.9 months, treatment with the combination regimen led to longer median OS compared with chemotherapy alone (41.9 vs 13.1 months; HR, 0.38).

As a result of long-term treatment with tislelizumab plus chemotherapy (≥35 cycles), 22 patients achieved a 4-year OS rate of 90.5 percent, an ORR of 100 percent, and the median DOR was not reached.

Among the 22 patients who received long-term treatment with tislelizumab plus chemotherapy (≥35 cycles), the 4-year OS rate was 90.5 percent, the ORR was 100 percent, and the median DoR was not reached.

Safety

The rates of grade ≥3 treatment-emergent adverse events (TEAEs) and serious TEAEs were higher in the tislelizumab plus chemotherapy arm than the chemotherapy alone arm (75.7 percent vs 48.6 percent and 43.2 percent vs 28.6 percent, respectively).

Neutropenia, thrombocytopenia, leukopenia, and anaemia were the most common grade ≥3 TEAs reported in both arms.

Immune-mediated AEs of any grade also occurred in 39.2 percent of patients in the tislelizumab plus chemotherapy arm, whereas only 5.7 percent were observed in the chemotherapy alone arm.

Nevertheless, the overall safety profile of tislelizumab plus chemotherapy was manageable and consistent with previous analyses, said the researchers.

“Overall, in patients with advanced nsq-NSCLC and tumour PD-L1 expression ≥50 percent, first-line tislelizumab plus chemotherapy demonstrated clinically meaningful improvements in PFS, OS, ORR, and DoR and a manageable safety profile compared with chemotherapy alone,” said the researchers.

“Long-term follow-up data demonstrated durable clinical improvement with tislelizumab plus chemotherapy,” the researchers noted.

“These findings support tislelizumab plus chemotherapy as a first-line treatment option for patients with locally advanced or metastatic nsq-NSCLC whose tumours exhibit high PD-L1 expression (≥50 percent),” they added.