Randomised controlled trials evaluating anticancer therapies in haematological cancers: an overview of global research activity

8 Jun 2023

Manju Sengar, Wilma M Hopman, Ghulam Rehman Mohyuddin, Aaron M Goodman, Bishal Gyawali, Deborah Mukherji, Nazik Hammad, CS Pramesh, Ajay Aggarwal, Richard Sullivan, Christopher M Booth

Background: Design, results, and interpretation of oncology randomised controlled trials (RCTs) have changed substantially over the past decade. In this study, we describe all RCTs evaluating anticancer therapies in haematological cancers published globally during 2014–2017 with comparisons with solid tumours RCTs.

Methods: A PubMed literature search identified all phase 3 RCTs of anticancer therapy for haematological cancers and solid tumours published globally during 2014–2017. Descriptive statistics, chi-square tests and the Kruskal–Wallis test were used to compare RCT design results, and output between haematological cancers and solid tumours as well as for different haematological cancer subtypes.

Results: 694 RCTs were identified; 124 in haematological cancers and 570 in solid tumours. Overall survival (OS) was the primary endpoint in only 12% (15/124) of haematological cancer trials compared to 35% (200/570) in solid tumours (p < 0.001). Haematological cancer RCTs evaluated the systemic novel therapy more often than the solid tumour RCT (98% versus 84%, p = 0.002). Use of surrogate endpoints like progression-free survival (PFS) and time to treatment failure (TTF) were more common in haematological cancers than solid tumours (47% versus 31%, p < 0.001). Within haematological cancers, the use of PFS and TTF was more prevalent in chronic lymphocytic leukaemia and multiple myeloma as compared to others (80%–81% versus 0%–41%, p < 0.001). Seventy-eight percent of haematologic trials were funded by industry as compared to 70% of solid tumour trials. Only 4% (5/124) of haematologicalcancer trials were led by investigators in upper-middle and lower-middle-income countries as compared to the 9% of solid tumour trials.

Conclusion: The fact that only 12% of haematological cancer RCTs are designed to show improvements in OS is of grave concern for the field and the care of future patients. This is further compounded by the highly prevalent use of alternative primary endpoints that are rarely valid surrogates for OS in haematological cancers.