Relationship between response rates and median progression‐free survival in non‐Hodgkin's lymphoma: A meta‐analysis of published clinical trials

Abstract

Demonstration of clinical effectiveness of a non-Hodgkin's lymphoma (NHL) treatment generally involves determination of progression-free survival (PFS). However, the long evaluation time of PFS limits its utility to make timely decisions in drug development. Therefore, the objective of this analysis was to determine the relationship between response rates and median PFS in NHL. A database was systematically developed from 513 identified NHL trials reported from 1996 to 2015. Potential predictors of the relationship between response rates and PFS were evaluated, including age, sex, treatment, percentage of treatment-naïve patients, and subtype of NHL. Seventy-three trials involving 86 cohorts were included in the meta-analysis. Linear regression analysis using logit of response rates and logarithm of median PFS indicated that the correlation between overall response rate (ORR) and median PFS was higher (R = 0.70) when compared to that of complete response (CR) rate and median PFS (R = 0.57). Furthermore, the correlation was improved with the addition of percentage of treatment-naïve patients and percentage of patients with follicular lymphoma (FL) (P < .005) between ORR and median PFS (R = 0.78), and between CR rate and median PFS relationship (R = 0.74). Treatment was not found to alter this relationship. In summary, ORR is as good as CR rate in predicting median PFS. Moreover, longer median PFS is expected in the trials including treatment-naïve and/or FL patients at a given ORR/CR rate. The determined relationship can be used to project the median PFS based on ORR or CR rate.

Pixantrone plus rituximab versus gemcitabine plus rituximab in patients with relapsed aggressive B‐cell non‐Hodgkin lymphoma not eligible for stem cell transplantation: a phase 3, randomized, multicentre trial (PIX306)

“…The CR rate was 35·5% (95% CI 28·0–43·6) with pixantrone + rituximab and 21·7% (95% CI 15·5–28·9) with gemcitabine + rituximab. However, response and survival outcomes do not always correlate in NHL (Lee et al , ; Zhu et al , ; Mangal et al , ).…”

Characterizing Exposure–Response Relationship for Therapeutic Monoclonal Antibodies in Immuno‐Oncology and Beyond: Challenges, Perspectives, and Prospects

“…For example, tumor size end points from tumor growth inhibition (TGI) model was used to link exposure and OS in exposure‐TGI‐OS models in an attempt to resolve the confounding effect by baseline prognostic disease marker 56–58 . The association between survival and a short‐term end point such as response rate 59–61 or TGI 58 has been shown in some indications, but more work needs to be done in this direction.…”

Copanlisib in non-Hodgkin's lymphoma and solid tumors: An efficacy and safety analysis

“…Although PFS and OS are considered to be better pri-mary endpoints for efficacy analysis, CR and ORR are increasingly being used as surrogate endpoints in hematological oncology, as they can be measured in a shorter time. A meta-analysis by Mangal et al concluded that both ORR and CR rates were found to predict median PFS, indicating the potential of these endpoints to make timely decisions in developing new NHL therapies 40) . In our analysis, median PFS and OS for NHL were reported in three studies.…”