Tiragolumab and atezolizumab in patients with PD-L1 positive non-small-cell lung cancer

Anti-PD-1 and anti-PD-L1 antibodies, alone or in combination with chemotherapy or anti-CTLA-4 antibodies, are standard therapeutic options for patients with advanced non-small-cell lung cancer (NSCLC). In patients with NSCLC with high PD-L1 expression (ie, with more than 50% of cancer cells staining positive for PD-L1 on immunohistochemistry), pembrolizumab or atezolizumab monotherapy can substantially improve objective response rates, progression-free survival, and overall survival compared with chemotherapy, sparing selected patients from chemotherapy. 1 Jassem J de Marinis F Giaccone G et al. Updated overall survival analysis from IMpower110: atezolizumab versus platinum-based chemotherapy in treatment-naive programmed death-ligand 1-selected NSCLC. J Thorac Oncol. 2021; 16: 1872-1882 Summary Full Text Full Text PDF PubMed Scopus (15) Google Scholar , 2 Reck M Rodríguez-Abreu D Robinson AG et al. Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score ≥ 50. J Clin Oncol. 2021; 39: 2339-2349 Crossref PubMed Scopus (114) Google Scholar Combining anti-PD-1 and anti-PD-L1 antibodies with chemotherapy for patients with non-squamous NSCLC with a high PD-L1 expression can push the median overall survival to 27·7–30·0 months (up from 20·2–26·3 months with pembrolizumab or atezolizumab monotherapy), although the combination can have higher adverse events. 3 Gray J Rodríguez-Abreu D Powell SF et al. FP13.02 Pembrolizumab + pemetrexed-platinum vs pemetrexed-platinum for metastatic NSCLC: 4-year follow-up from KEYNOTE-189. J Thorac Oncol. 2021; 16: S224 Summary Full Text Full Text PDF Google Scholar , 4 Socinski MA Nishio M Jotte RM et al. IMpower150 final overall survival analyses for atezolizumab plus bevacizumab and chemotherapy in first-line metastatic nonsquamous NSCLC. J Thorac Oncol. 2021; 16: 1909-1924 Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar Immunotherapy combinations such as nivolumab plus ipilimumab (with or without chemotherapy) are also standard regimens, but do not appear to add benefit versus single agents, as shown by a median overall survival of 21·2 months reported in a high-PD-L1 population. 5 Paz-Ares LG Ramalingam SS Ciuleanu T-E et al. First-line nivolumab plus ipilimumab in advanced NSCLC: 4-year outcomes from the randomized, open-label, phase 3 CheckMate 227 part 1 trial. J Thorac Oncol. 2022; 17: 289-308 Summary Full Text Full Text PDF PubMed Scopus (25) Google Scholar Therefore, there is an unmet need to improve outcomes for patients with NSCLC with a high expression of PD-L1, by use of immunotherapy combinations that dispense with the need for upfront chemotherapy. Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 studyTiragolumab plus atezolizumab showed a clinically meaningful improvement in objective response rate and progression-free survival compared with placebo plus atezolizumab in patients with chemotherapy-naive, PD-L1-positive, recurrent or metastatic NSCLC. Tiragolumab plus atezolizumab was well tolerated, with a safety profile generally similar to that of atezolizumab alone. These findings demonstrate that tiragolumab plus atezolizumab is a promising immunotherapy combination for the treatment of previously untreated, locally advanced unresectable or metastatic NSCLC. Full-Text PDF