Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First-line Treatment for Advanced Squamous Non–Small-Cell Lung Cancer

Abstract

IMPORTANCE This study demonstrates that tislelizumab in combination with chemotherapy is associated with improved progression-free survival (PFS) in patients with advanced squamous non-small-cell lung cancer (sq-NSCLC).OBJECTIVE To assess the efficacy and safety/tolerability of tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for patients with advanced sq-NSCLC. DESIGN, SETTING, AND PARTICIPANTSThis open-label, randomized phase 3 clinical trial was conducted at 46 sites in China between July 2018 and June 2019 and included patients with treatment-naive, histologically confirmed stage IIIB/IV sq-NSCLC. The data cutoff for these analyses was December 6, 2019; data extraction occurred on January 7, 2020.INTERVENTIONS Patients were randomized (1:1:1) to receive 1 of the following regimens intravenously on a 21-day cycle: tislelizumab (200 mg, day 1) plus paclitaxel (175 mg/m 2 , day 1) and carboplatin (area under the concentration of 5, day 1) (arm A); tislelizumab plus nab-paclitaxel (100 mg/m 2 , days 1, 8, and 15) and carboplatin (arm B); and paclitaxel and carboplatin (arm C). Patients were stratified by disease stage and tumor programmed cell death 1 ligand 1 (PD-L1) expression (<1% vs 1%-49% vs Ն50%). MAIN OUTCOMES AND MEASURESThe primary end point was progression-free survival (PFS) assessed by an independent review committee (IRC). Secondary end points included overall survival, investigator-assessed (INV) PFS, IRC-assessed objective response rate (ORR), and IRC-assessed duration of response, as well as the incidence and severity of adverse events (AEs). RESULTSOverall, 355 patients (median [range] age, 62 [34-74] years; 330 men [91.7%]) with sq-NSCLC received treatment. After a median study follow-up of 8.6 months (95% CI, 8.1-9.0 months), IRC-assessed PFS was significantly improved with tislelizumab plus chemotherapy (arm A, 7.6 months; arm B, 7.6 months) vs chemotherapy alone (arm C, 5.5 months; hazard ratios were 0.524 (95% CI, 0.370-0.742; P < .001 [A vs C]) and 0.478 (95% CI, 0.336-0.679; P < .001 [B vs C]). Higher IRC-assessed ORR and longer IRC-assessed duration of response were observed in arms A (72.5%; 8.2 months) and B (74.8%; 8.6 months) vs C (49.6%; 4.2 months). No association was observed between PD-L1 expression and IRC-assessed PFS or ORR. Discontinuation of any treatment because of AEs was reported in 15 (12.5%; arm A), 35 (29.7%; arm B), and 18 (15.4%; arm C) patients. In each arm, the most common grade of 3 or greater AE was decreased neutrophil levels, which aligned with known chemotherapy toxic effects. Six treatment-related AEs leading to death occurred; however, no deaths were solely attributed to tislelizumab. CONCLUSIONS AND RELEVANCEIn this phase 3 randomized clinical trial, adding tislelizumab to chemotherapy was associated with significantly prolonged IRC-assessed PFS, higher IRC-assessed ORRs, and a manageable safety/tolerability profile in patients with advanced sq-NSCLC, regardless of PD-L1 expression.TRIAL REGISTRATION ClinicalTrials.gov Identifier:...

The effect of smoking status on efficacy of immune checkpoint inhibitors in metastatic non-small cell lung cancer: A systematic review and meta-analysis

“…1 . Finally, 28 eligible articles reporting 24 RCTs (23 phase 3 and 1 phase 2 trials) with 13918 patients (11698 of smokers and 2220 of never smokers) were eligible for inclusion [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] . Because one studies [10] provided pooled OS data of CheckMate-017 [9] , and -057 [11] , the pooled data were used instead of data from the individual trials in this meta-analysis.…”

“…Therefore, never smokers should obtain less benefit from ICIs compared to smokers theoretically. However, this hypothesis has not been confirmed by current ICIs trials, in which inconsistent results were observed [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] . Some previous meta-analyses [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] have attempted to clarify the relationship between smoking and the efficacy of ICIs in NSCLC, while the lack of statistical power due to limitations such as small number of studies, small sample size, and few subgroup analysis prevents a final conclusion.…”

The landscape of immune checkpoint inhibitor therapy in advanced lung cancer

“…1 ). In total, 38 RCTs, including 41 studies with 20,173 patients with lung cancer, were included for quantitative analyses [ 6 – 8 , 14 – 48 ]. Eight studies explored the efficacy of ICI versus SOC in patients with SCLC (three studies on ipilimumab, two on atezolizumab, one on nivolumab, one about durvalumab, and one assessing tremelimumab plus durvalumab).…”

Research progress in immune checkpoint inhibitors for lung cancer in China

“…44 One study assessing the efficacy activity and safety of camrelizumab in patients with previously treated, advanced NSCLC negative for oncogenic drivers reported trAEs (all grades) in 69.0% of the 25 enrolled patients. 45 The phase III study 39 of tislelizumab plus chemotherapy versus chemotherapy alone as a first-line treatment for advanced squamous NSCLC demonstrated trAEs in 12.5%, 29.7%, and 15.4% of patients in the tislelizumab + paclitaxel + carboplatin, tislelizumab + nab-paclitaxel + carboplatin, and paclitaxel + carboplatin arms, respectively. No new safety signals were identified upon addition of tislelizumab to chemotherapy.…”