Tislelizumab plus chemotherapy vs. pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials

Background: Pembrolizumab (PEM) and tislelizumab (TIS), in combination with chemotherapy, have demonstrated significant clinical benefits in first-line treatment of advanced non-small cell lung cancer (NSCLC). However, no head-to-head clinical trial has yet compared these two treatments. Methods: We conducted a literature search of randomized trials, in which TIS plus chemotherapy or PEM plus chemotherapy were studied for the first-line treatment of NSCLC. Randomized design and the endpoint of progression-free survival (PFS) were the inclusion criteria for our analysis. Adjusted indirect comparison between TIS and PEM was performed by application of the IPDfromKM-Shiny method. This method is based on the reconstruction of individual patient data from Kaplan-Meier curves. Outcomes in terms of PFS were expressed as hazard ratio (HR) with 95% and 90% confidence interval (CI). Results: Data were extracted from five randomized trials involving nearly2,000 participants. In comparing PEM plus chemotherapy (n=748) or TIS plus chemotherapy (n=462) vs. chemotherapy alone (n=782), the Shiny method found a significant advantage in terms of PFS (HR =0.5856, 95% CI: 0.4986-0.6876 for TIS; HR =0.5573, 95% CI: 0.4969-0.6251 for PEM), thus confirming the results of the original trials. The indirect comparison of PEM plus chemotherapy vs. TIS plus chemotherapy showed a substantial equivalence between these two regimens (HR =0.952; 95% CI: 0.775-1.168; 90% CI: 0.801-1.130) suggesting an acceptable degree of equivalence according to regulatory criteria. Medians were 8.89 months for PEM combination, 7.97 months for TIS combination, and 5.69 for the controls. Conclusions: The PFS of TIS combined with chemotherapy was similar to that of PEM combined with chemotherapy. Based on the HR with 90% CI, these two agents met an equivalence criterion for PEM vs. TIS ranging from -19.9% to +13.0%.