Tislelizumab benefit demonstrated in advanced nonsquamous NSCLC
medwireNews: The addition of tislelizumab to first-line chemotherapy significantly improves the progression-free survival (PFS) of patients with locally advanced or metastatic nonsquamous non-small-cell lung cancer (NSCLC), indicate phase 3 trial results.
The risk for disease progression or death was reduced by around 35% among patients who did versus did not receive the novel PD-1 inhibitor alongside chemotherapy, report Shun Lu, from Shanghai Chest Hospital in China, and team in the Journal of Thoracic Oncology.
They note, however, that “RATIONALE 304 was conducted entirely in China and the percentage of nonsmokers was much higher than what is typical in clinical trials of Western patient populations,” and the results may therefore not translate to a more heterogeneous patient population.
Nevertheless, the researchers believe that “the homogeneous nature of the patient population in RATIONALE 304 suggests that Asian patients, particularly those expressing high levels of PD-L1, could benefit from treatment with tislelizumab.”
The study investigators enrolled 334 treatment-naïve patients with stage IIIB–IV nonsquamous disease lacking sensitizing EGFR or ALK alterations, and randomly assigned them to receive four to six cycles of carboplatin AUC 5 or cisplatin 75 mg/m2 plus pemetrexed 500 mg/m2 every 3 weeks either with or without tislelizumab 200 mg, followed by maintenance with tislelizumab plus pemetrexed and pemetrexed alone, respectively.
After a median follow-up of 9.8 months, median PFS as assessed by independent review was 9.7 months in the tislelizumab plus chemotherapy group (n=223) and 7.6 months in the chemotherapy alone group (n=111), a significant difference giving a hazard ratio (HR) for progression or death of 0.645 in favor of the combination.
The PFS rates at 12 months were 31.3% and 16.7%, respectively.
When stratified by tumor cell PD-L1 expression, the PFS benefit afforded by the addition of tislelizumab was significant among patients with expression levels of at least 50%, with an HR of 0.308, but not among those with levels of 1–49% (nonsignificant HR=1.058).
And a post-hoc exploratory interaction analysis suggested that PD-L1 levels of 50% or more “may be a possible predictor of PFS benefit,” say Lu and colleagues.
The objective response rate was also higher in the tislelizumab–chemotherapy arm than in the chemotherapy alone arm, at 57.4% versus 36.9%, and the median duration of response was also longer, at 8.5 versus 6.0 months.
Median overall survival was not reached at the time of data cutoff for this interim analysis, note the researchers.
Reporting on the safety, they say that adverse events (AEs) in the tislelizumab group “were consistent with the known tolerability profile of PD-1 inhibitors in combination with chemotherapy and were also consistent with previous reports of tislelizumab combination therapy.”
The most common AEs of grade 3–5 in the tislelizumab and control groups were neutropenia (44.6 vs 35.5%), leukopenia (21.6 vs 14.5%), thrombocytopenia (19.4 vs 13.6%), and anemia (14.9 vs 11.8%).
A total of 25.7% of tislelizumab-treated patients and 9.1% of those given chemotherapy alone discontinued any treatment component due to treatment-emergent AEs. Dose modifications of tislelizumab were needed by 59.9% of patients and 11.3% discontinued the drug.
There were three deaths due to treatment-related AEs in the tislelizumab arm and one in the control arm; all four deaths were due to pneumonitis.
The team concludes that tislelizumab plus chemotherapy could be “a new potential option for first-line treatment of advanced [nonsquamous]-NSCLC irrespective of disease stage.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group