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First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. Horn Leora,Mansfield Aaron S,Szczęsna Aleksandra,Havel Libor,Krzakowski Maciej,Hochmair Maximilian J,Huemer Florian,Losonczy György,Johnson Melissa L,Nishio Makoto,Reck Martin,Mok Tony,Lam Sivuonthanh,Shames David S,Liu Juan,Ding Beiying,Lopez-Chavez Ariel,Kabbinavar Fairooz,Lin Wei,Sandler Alan,Liu Stephen V, The New England journal of medicine BACKGROUND:Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy. METHODS:We conducted this double-blind, placebo-controlled, phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive-stage small-cell lung cancer who had not previously received treatment. Patients were randomly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21-day cycles (induction phase), followed by a maintenance phase during which they received either atezolizumab or placebo (according to the previous random assignment) until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical benefit. The two primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat population. RESULTS:A total of 201 patients were randomly assigned to the atezolizumab group, and 202 patients to the placebo group. At a median follow-up of 13.9 months, the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio for death, 0.70; 95% confidence interval [CI], 0.54 to 0.91; P=0.007). The median progression-free survival was 5.2 months and 4.3 months, respectively (hazard ratio for disease progression or death, 0.77; 95% CI, 0.62 to 0.96; P=0.02). The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents, with no new findings observed. CONCLUSIONS:The addition of atezolizumab to chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by F. Hoffmann-La Roche/Genentech; IMpower133 ClinicalTrials.gov number, NCT02763579 .). 10.1056/NEJMoa1809064
[Immunotherapy of lung cancer]. Ostoros Gyula Magyar onkologia Immune checkpoint inhibitor therapy in lung cancer is a new effective treatment as part of a complex treatment strategy. In the advanced stage of non-small cell non-squamous lung cancer, without actionable mutation, the immune monotherapy or combination treatment with platinum based chemotherapy is a new standard of care depending on PD-L1 status. In case of advanced squamous cell lung cancer the situation is similar. The exact role of combination PD-1 axis and CTLA-4 inhibitor treatment with or without chemotherapy is not exactly defined. Immune checkpoint inhibitor therapy can be used in second or more line treatment as well. After exhaustion of targeted treatment the efficacy of the combination of immunotherapy with angiogenesis inhibitor and platinum based chemotherapy is promising. In locally advanced non-small cell lung cancer after radiochemotherapy the consolidation PD-L1 inhibitor treatment is a new standard of care in case of PD-L1 positivity. There are Phase III trials in neoadjuvant and adjuvant setting as well. In extensive stage small cell lung cancer the platinum-etoposide treatment with PD-L1 inhibitor is a new standard, but we do not have any effective biomarkers yet.