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20-05-2022 | Oncology | News | Article

First-line tiragolumab–atezolizumab promising for PD-L1-positive advanced NSCLC

Author: Shreeya Nanda

medwireNews: Previously untreated patients with PD-L1-positive advanced non-small-cell lung cancer (NSCLC) could benefit from the combination of tiragolumab plus atezolizumab, indicate phase 2 trial data.

The combination “showed a clinically meaningful improvement in objective response rate [ORR] and progression-free survival [PFS] compared with placebo plus atezolizumab” in this patient population, report Byoung Chul Cho (Yonsei University College of Medicine, Seoul, South Korea) and fellow CITYSCAPE investigators.

The benefit was “more pronounced” in the subgroup of participants with high PD-L1 levels, defined as a tumor proportion score (TPS) of at least 50%, they write in The Lancet Oncology.

The team continues: “The preliminary efficacy and safety of tiragolumab plus atezolizumab as a first-line treatment in patients with PD-L1 high (TPS ≥50%) NSCLC observed in this phase 2 study is being confirmed in an ongoing phase 3 study (SKYSCRAPER-01; NCT04294810).”

In the double-blind trial, 135 patients with locally advanced or metastatic NSCLC lacking EGFR or ALK alterations were randomly assigned to receive either the anti-TIGIT antibody tiragolumab at a dose of 600 mg or placebo on day 1 of each 3-weekly cycle alongside atezolizumab 1200 mg also given on day 1.

The primary analysis – conducted at a median follow-up of 5.9 months – showed a significant improvement in both ORR and PFS, as assessed by investigators, in the tiragolumab plus atezolizumab group relative to the placebo plus atezolizumab group, at rates of 31.3% versus 16.2% and median PFS times of 5.4 versus 3.6 months (hazard ratio [HR] for progression or death=0.57).

The ORR and PFS results were similar in an updated analysis at a median follow-up of 30.4 months, and at this timepoint there was also a numerical improvement in overall survival with the addition of tiragolumab to atezolizumab, at a median of 23.2 months versus 14.5 months with placebo plus atezolizumab (nonsignificant HR for death=0.69).

Cho and colleagues also analyzed outcomes by PD-L1 expression, assessed using the 22C3 immunohistochemistry pharmDx assay (Agilent Technologies, Santa Clara, California, USA), and found that the benefit afforded by tiragolumab addition was driven primarily by patients with PD-L1 levels of at least 50%.

For instance, in this subgroup, the ORRs with the combination and atezolizumab alone were 69.0% and 24.1%, respectively, while the corresponding rates in the subgroup with PD-L1 levels of 1–49% were 16% and 18%.

Similarly, the median overall survival times were unreached with tiragolumab and 12.8 months with placebo among patients with PD-L1 levels of 50% or more, and were a respective 13.3 and 14.5 months among those with levels of 1–49%.

“The overall safety profile of tiragolumab plus atezolizumab observed in this study was generally similar to that of placebo plus atezolizumab and was consistent with phase 1 data,” say the researchers.

Treatment-related adverse events (TRAEs) of any grade occurred in 82% of tiragolumab-treated patients and 71% of those given placebo. The most frequent TRAE of grade 3 or higher was lipase elevation, observed in 9% of the tiragolumab group and 3% of the placebo group. Two deaths in the tiragolumab plus atezolizumab study arm were attributed to treatment; one case each of pyrexia and infection.

The incidence of immune-mediated AEs was higher in the tiragolumab than placebo group, at 76% versus 47%, but these “were generally low-grade and manageable, mostly consisting of infusion-related reactions and rash, in line with previous findings for immunotherapies,” note Cho et al.

And they conclude: “These findings demonstrate that tiragolumab plus atezolizumab is a promising immunotherapy combination for the treatment of previously untreated, locally advanced unresectable or metastatic NSCLC.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Lancet Oncol 2022; doi:10.1016/S1470-2045(22)00226-1

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