Adjuvant everolimus is not associated with improved disease-free survival (DFS) among patients with diffuse large B-cell lymphoma (DLBCL) who are already in complete response (CR), according to results from a randomized phase III trial (PILLAR-2).
Patients with high-risk DLBCL (International Prognostic Index [IPI] of at least 3) have an increased risk for relapse following CR to first-line rituximab-based chemotherapy.
To determine whether 1 year of adjuvant everolimus could improve DFS in this patient population, Thomas E Witzig, MD, Mayo Clinic (Rochester, MN), and colleagues assessed 742 patients with high-risk DLBCL and positron emission tomography/computed tomography (PET/CT)-confirmed CR to first-line rituximab-based chemotherapy. Median follow-up lasted 50.4 months.
Between August 2009 and December 2013, patients were randomly assigned to receive 1 year of either 10 mg/day everolimus (n = 372) or placebo (n = 370). The primary endpoint was DFS, and secondary endpoints included overall survival (OS), lymphoma-specific survival (LSS), and safety.
Results of the study were published in Annals of Oncology (online December 15, 2017; doi:10.1093/annonc/mdx764).
Ultimately, 48% of patients completed everolimus, and 67% completed placebo. Primary reasons for discontinuation of everolimus vs placebo included adverse events (30% vs 12%), and relapsed disease (6% vs 13%).
The researchers did not observe significant improvements in DFS with everolimus vs placebo (hazard ratio [HR] 0.92). Two-year DFS rates for everolimus and placebo were 77.8% and 77.0%, respectively.
The most commonly reported grade 3/4 adverse events with everolimus included neutropenia, stomatitis, and decreased cluster of differentiation 4 (CD4) lymphocytes.
“Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR,” the researchers concluded. “Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained.”—Christina Vogt