1. Progression-free survival was longer for patients receiving tiragolumab with atezolizumab as compared to placebo

2. The combination arm had a signal of inducing increase lipase compared to atezolizumab alone

Evidence Rating Level: 2 (Good)

Study Rundown: This study explored the impact of tiragolumab with atezolizumab as compared to placebo with atezolizumab a first-line treatment for non-small-cell lung cancer (NSCLC) that is unresectable or metastatic. Atezolizumab is indicated in the first line setting for NSCLC and this study investigated the addition tiragolumab, a new antibody directed against TIGT, a new target for immune blockade to promote anti-tumour activity. Prior dual blockade with CTLA-4 and PD-1/PD-L1 improved survival over chemotherapy but were not definitively compared against single agent immunotherapy alone. Primary outcomes included progression-free survival (PFS) and objective response rate (ORR). Secondary outcomes included safety, as measured by adverse events. In the tiragolumab plus atezolizumab group, median PFS was 5.4 months as compared to 3.6 months in the placebo with atezolizumab group. ORR was higher in the treatment group compared to the placebo group. Serious treatment-related adverse events (AEs) were noted in both groups (14 patients from the test group and 12 from the placebo group). An increase in lipase was the most commonly reported severe treatment-related AE in both groups. The test group population had 2 treatment-related deaths. Limitations to this study include inadequate power regarding ORR and PFS as this was a phase 2 trial and the lack of mature data. Overall, tiragolumab with atezolizumab presents a possible first-line treatment option for PD-L1 positive advanced or metastatic NSCLC which is being confirmed in a phase 3 study and highlights the potential of TIGT inhibition as a new clinically important pathway for cancer immunotherapy.

Click to read the study in The Lancet Oncology

Relevant Reading: Nivolumab plus ipilimumab in advanced non–small-cell lung cancer.

In-Depth [randomized controlled trial]: This international, randomized, phase 2, double-blinded study conducted in centres from the USA, Asia, and Europe randomly assigned 135 adult patients with advanced unresectable or metastatic NSCLC on a 1:1 basis into two groups. Every three weeks, patients received either 600mg of tiragolumab with 1200mg of atezolizumab or placebo plus atezolizumab by intravenous. In the tiragolumab plus atezolizumab group, median PFS was 5.4 months (95% confidence interval (CI), 4.2 – not estimable), whereas in the placebo with atezolizumab group it was 3.6 months (95% CI, 2.7 – 4.4 months). In the treatment group, 21 patients (31.3%, 95 CI, 19.5-43.2%) had an objective response, as compared to 11 patients (16.2%, 95% CI, 6.7-25.7%) in the placebo group. At a median duration of follow-up of 30.4 months, the median OS in the combination therapy arm was 23.2 months vs. 14.5 months in the single agent and placebo arm (HR 0.69, 95% CI, 0.44 – 1.07, p = 0.093). Tumour proportion score (TPS) was used to subdivide the treatment response. There was improved OS in the TPS ≥50% but not in the 1-49% group. Treatment-related AEs were common in both the combination arm and comparator arms (82% vs. 71%). There was some increased grade 1-2 rash and pruritis in the combination group and some signal of increased lipase levels as well but the phase 3 study will help elucidate whether there is a higher immune-related pancreatitis adverse event in the dual blockade arm.

Image: PD

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