Association of progression-free or event-free survival with overall survival in diffuse large B-cell lymphoma after immunochemotherapy: a systematic review

Abstract

To investigate progression-free survival (PFS) and event-free survival (EFS) as early efficacy endpoints in diffuse large B-cell lymphoma (DLBCL), this systematic review included phase III randomized controlled trials (RCTs), phase II trials, and retrospective studies in newly diagnosed DLBCL receiving rituximab-containing chemotherapy through databases search up to 2019. Quality control was performed, where studies with high risk of bias were excluded. Prediction models were first established using the RCTs, and then externally validated in the phase II and retrospective populations. Trial-level surrogacy analysis was conducted by correlating the logarithmic (log) hazard ratio (HR) for PFS or EFS and log HR for OS. Correlation analysis at treatment arm-level was performed between 1-, 2-, 3-, and 5-year PFS or EFS rates and 5-year OS. The correlation was evaluated using the Pearson correlation coefficient r in weighted linear regression, with weight equal to patient size. Sensitivity analyses were performed to assess the consistency of predictive model by leaving one subgroup of trials out at a time. Twenty-six phase III RCTs, 4 phase II trials and 47 retrospective studies were included. In trial-level surrogacy, PFS (r, 0.772; 95% confidence interval [CI], 0.471–0.913) or EFS (r, 0.838; 95% CI, 0.625–0.938) were associated with OS. For rituximab immunochemotherapy treatment arms in RCTs, there was a linear correlation between 1 and 5-year PFS (r, 0.813–0.873) or EFS (r, 0.853–0.931) and 5-year OS. Sensitivity analysis demonstrated reasonable overall consistency. The correlation between PFS and OS was externally validated using independent phase II, and retrospective data (r, 0.795–0.897). We recommend PFS and EFS as earlier efficacy endpoints in patients with DLBCL primarily treated with rituximab-containing immunochemotherapy.

Progression-free survival at 24 months and subsequent survival of patients with extranodal NK/T-cell lymphoma: a China Lymphoma Collaborative Group (CLCG) study

“…Consistent with the present finding, the subsequent survival of patients with DLBCL or PTCL who achieved EFS24 or PFS24 is almost equal to that of the age-, sex-, and country-matched general population [26][27][28][29]32]. Furthermore, we have confirmed the association of PFS24 with OS in trial-and treatment armlevel in RCTs on DLBCL patients treated with immunochemotherapy; its association has been externally validated using the literature-based data from high-quality phase II and retrospective studies [40]. Similarly, in patients with follicular lymphoma and marginal zone lymphomas [39,41], early progression of disease within 24 months after initial treatment stratified subsequent OS and identifies a high-risk population.…”

Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma

“…Event-free survival is a widely accepted, robust early efficacy end point in clinical trials involving patients with large B-cell lymphoma, on the basis of retrospective analyses of randomized trials that have shown a correlation between improvements in event-free survival and overall survival. [19][20][21] Patients with relapsed or refractory large B-cell lymphoma who do not have a response to salvage chemotherapy (i.e., who have progressive or stable disease) will not benefit from high-dose chemotherapy with autologous stem-cell transplantation. 22 In this scenario, a change to third-line therapy is indicated, sometimes in the absence of progressive disease.…”

Progression-Free Survival and Time to Progression as Potential Surrogate Endpoints for Overall Survival in Chemoradiotherapy Trials in Limited-Stage Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…There has been debate on how a surrogate endpoint should be considered as valid. We employed the correlation approach which has been used to assess the possibility of PFS or TTP as a surrogate endpoint for OS in locally advanced NSCLC (11), nasopharyngeal carcinoma (8), and diffuse large B-cell lymphoma (10). Candidate surrogate endpoints could be valid only if the correlation coefficient was greater than 0.75 (55).…”

“…For example, crizotinib was approved for anaplastic lymphoma kinasepositive non-small-cell lung cancer on the basis of PFS (6) and sunitinib for gastrointestinal stromal tumor and renal cell carcinoma on the basis of TTP (7). PFS and TTP have also been demonstrated to be valid surrogate endpoints for OS in some malignancies (8)(9)(10)(11)(12). However, an early valid surrogate endpoint has never been reported in LS-SCLC patients.…”