BEAT-SC Trial: Phase 3 Study of Bevacizumab or Placebo With Atezolizumab and Platinum-Based Chemotherapy in ES-SCLC

Atezolizumab, in combination with carboplatin and etoposide, has received approval as the first-line therapy for patients diagnosed with extensive-stage small cell lung cancer (ES-SCLC), following the findings from the phase 1/3 IMpower133 trial (NCT02763579). Additionally, the VEGF inhibitor bevacizumab is authorized for use in various tumor types and exhibits synergistic effects when paired with atezolizumab, as evidenced by the phase 3 IMpower150 study (NCT02366143) conducted in non-small cell lung cancer. BEAT-SC (jRCT2080224946) is assessing the effectiveness and safety of bevacizumab in combination with atezolizumab and platinum-based chemotherapy for patients diagnosed with ES-SCLC in Japan and China. The primary analysis revealed that the inclusion of bevacizumab resulted in improved progression-free survival (PFS) when combined with atezolizumab and either cisplatin or carboplatin plus etoposide (ACE). The initial interim data on overall survival (OS) were deemed immature.1 At ESMO 2024, the findings from the second interim analysis of OS data were presented.2

Patients eligible for the study had measurable ES-SCLC, were aged ≥20 years (or ≥18 years for participants in China), had an ECOG performance status of 0 or 1, and had not received any prior systemic treatment for ES-SCLC. Participants were randomly assigned 1:1 to undergo 4 cycles of induction therapy, each lasting 21 days, with either bevacizumab combined with ACE or a placebo combined with ACE. This was followed by maintenance therapy consisting of bevacizumab plus atezolizumab or a placebo plus atezolizumab, respectively. The primary end point of the study was PFS as assessed by investigators (INV-PFS), while key secondary end points included OS, safety, and subgroup analysis.

At the data cutoff of January 10, 2024, with a median follow-up period of 12.42 months, the median INV-PFS was 5.7 months for the combination of bevacizumab and ACE, compared with 4.4 months for the placebo plus ACE group. Additionally, the median OS was 13.9 months for the bevacizumab plus ACE cohort, in contrast to 16.4 months for the placebo plus ACE cohort (P=.3995). The safety analysis population comprised 166 patients in the bevacizumab plus ACE arm and 164 patients in the placebo plus ACE arm. Serious treatment-related adverse events (TRAEs) and grade 5 TRAEs had similar frequency between the bevacizumab plus ACE versus the placebo plus ACE arms (35.5% vs 36.6% and 3.0% vs 4.9%). The most common reasons for early discontinuation of all treatments were withdrawal by the patient (6.0% vs 2.4%) and death (4.8% vs 3.0%). Two patients in each arm discontinued treatment due to an adverse event.

This analysis indicates that the inclusion of bevacizumab with ACE resulted in a favorable PFS compared with the combination of placebo and ACE, aligning with the findings of the primary analysis. At the time of the second interim OS analysis, the OS data remained immature, and a numerical improvement in OS for the bevacizumab plus ACE combination was not observed when compared with placebo plus ACE. There will be continued follow-up for OS. No new safety concerns were identified.

Sources:

  1. Ohe Y, Han B, Nishio M, et al. BEAT-SC: a randomized phase III study of bevacizumab or placebo in combination with atezolizumab and platinum-based chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). J Clin Oncol. 2024;42:8001-8001.
  2. Han B, Ohe Y, Nishio M, et al. Second OS interim analysis from BEAT-SC: a randomized phase III study of bevacizumab (bev) or placebo in combination with atezolizumab and platinum-based chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). Barcelona, Spain, & online: presented at ESMO Congress 2024; abstract 1789P.

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