#VisualAbstract: Tislelizumab plus chemotherapy improves outcomes for advanced squamous non small cell lung cancer over chemotherapy alone

1. Tislelizumab, a monoclonal antibody and PD1/L1 inhibitor, when combined with chemotherapy, showed significantly prolonged progression free survival and higher objective response rate, compared with chemotherapy alone.

Evidence Rating Level: 1 (Excellent)

Squamous non-small-cell lung cancers (sq-NSCLCs) are often diagnosed at a later stage, leading to poor prognosis and difficult disease management. However, there has been promise shown when combining chemotherapy with monoclonal antibody treatments that block programmed cell death receptor 1 and its ligand (PD-1/L1 inhibitors). The sole approved treatment for advanced sq-NSCLC is a PD-1/L1 inhibitor (pembrolizumab) and standard chemo. This led to research into the potential of tislelizumab, a monoclonal antibody of the same class. Early trials showed that combining tislelizumab with platinum-based therapy was well tolerated, demonstrated antitumour activity, and had an 80% or 67% objective response rate, depending on the chemo regimen used. This current study was a phase 3 trial examining the efficacy and safety of tislelizumab plus chemotherapy for advanced sq-NSCLC.  The study population consisted of 360 patients (median [range] age of 62 [34-74] years; 91.7% male) with stage IIIb or IV sq-NSCLC. They were randomized roughly equally into 3 arms: Arm A consisted of tislelizumab plus paclitaxel and carboplatin, Arm B consisted of tislelizumab plus nab-paclitaxel and carboplatin, and Arm C consisted of paclitaxel and carboplatin (no tislelizumab). These regimens were administered intravenously every 3 weeks, and the outcomes investigated were progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR), all assessed by an independent review committee. After a median follow-up of 8.6 months, the PFS was 7.6 months in Arms A and B, compared to 5.5 months in Arm C (hazard ratio 0.524, 95% CI 0.370-0.742, p < 0.001 for Arm A vs C; HR 0.478, 95% CI 0.336-0.679, p < 0.001 for Arm B vs C). The arms with tislelizumab experienced higher ORRs and longer DOR, which were 72.5% and 8.2 months in Arm A, 74.8% and 8.6 months in Arm B, and 49.% and 4.2 months in Arm C. In terms of adverse events, discontinuation due to treatment was found in 12.5% of Arm A, 29.7% of Arm B, and 15.4% of Arm C. The adverse events found were consistent with known adverse events of chemotherapy. Overall, this study demonstrated that tislelizumab combined with chemotherapy significantly reduced the risk for progression or death in advanced squamous non-small-cell lung cancer patients.

Click to read the study in JAMA Oncology

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