Search

Lay abstract Extended-stage small-cell lung cancer (ES-SCLC) is a highly aggressive lung cancer subtype, accounting for 13-15% of all lung cancers. For several years, the standard treatment for this disease was based on polychemotherapy, with a rapid disease response but with an equally rapid disease progression. The new standard treatment has recently been changed, based on the results of two large clinical trials, which showed the efficacy and safety of the combination of chemotherapy with immunotherapy compared to chemotherapy alone. Nevertheless, prognosis of ES-SCLC remains poor, and new treatment strategies are urgently needed. Therefore, we designed the CeLEBrATE trial to investigate whether the combination of chemotherapy with antiangiogenetic therapy and immunotherapy is safe and could improve survival in patients with ES-SCLC.Based on improved survival from the addition of PD-L1 inhibitors in phase III trials, the combination of immunotherapy and platinum-doublet chemotherapy has become the new standard treatment for extended-stage small-cell lung cancer (ES-SCLC). Furthermore, the antiangiogenetic agent bevacizumab showed a longer progression-free survival by targeting VEGF that has pleiotropic effects, including immunosuppressive ones. We, therefore, hypothesized that targeting angiogenesis would improve the efficacy of chemoimmunotherapy. The CeLEBrATE trial is an open-label, multicenter, phase II study designed to assess the efficacy and safety of the combination of carboplatin and etoposide plus bevacizumab and atezolizumab in treatment-naive patients with ES-SCLC. The primary end point is overall survival rate at 1 year, while secondary end points include overall response rate, progression-free survival and toxicity.

Purpose Considering promising results in phase II studies, a randomized phase III trial was designed to assess the efficacy of adding bevacizumab to first-line cisplatin plus etoposide for treatment of extensive-disease (ED) small-cell lung cancer (SCLC). Patients and Methods Treatment-naive patients with ED-SCLC were randomly assigned to receive either cisplatin plus etoposide (arm A) or the same regimen with bevacizumab (arm B) for a maximum of six courses. In the absence of progression, patients in arm B continued bevacizumab alone until disease progression or for a maximum of 18 courses. The primary end point was overall survival (OS). Results Two hundred four patients were randomly assigned and considered in intent-to-treat analyses (103 patients in arm A and 101 patients in arm B). At a median follow-up of 34.9 months in arm A and arm B, median OS times were 8.9 and 9.8 months, and 1-year survival rates were 25% and 37% (hazard ratio, 0.78; 95% CI, 0.58 to 1.06; P = .113), respectively. A statistically significant effect of bevacizumab on OS in patients who received maintenance was seen (hazard ratio, 0.60; 95% CI, 0.40 to 0.91; P = .011). Median progression-free survival times were 5.7 and 6.7 months in arm A and arm B, respectively ( P = .030). Regarding hematologic toxicity, no statistically significant differences were observed; for nonhematologic toxicity, only hypertension was more frequent in arm B (grade 3 or 4, 1.0% v 6.3% in arms A v B, respectively; P = .057). Conclusion The addition of bevacizumab to cisplatin and etoposide in the first-line treatment of ED-SCLC had an acceptable toxicity profile and led to a statistically significant improvement in progression-free survival, which, however, did not translate into a statistically significant increase in OS. Further research with novel antiangiogenic agents, particularly in the maintenance setting, is warranted.