Real-world validity of randomized controlled phase III trials in newly diagnosed glioblastoma: to whom do the results of the trials apply?

Erlend Skaga; Marthe Andrea Skretteberg; Tom Børge Johannesen; Petter Brandal; Einar O Vik-Mo; Eirik Helseth; Iver A Langmoen

doi:10.1093/noajnl/vdab008

Real-world validity of randomized controlled phase III trials in newly diagnosed glioblastoma: to whom do the results of the trials apply?

Neurooncol Adv. 2021 Feb 26;3(1):vdab008. doi: 10.1093/noajnl/vdab008. eCollection 2021 Jan-Dec.

Authors

Erlend Skaga¹, Marthe Andrea Skretteberg², Tom Børge Johannesen³, Petter Brandal⁴, Einar O Vik-Mo¹, Eirik Helseth^{1

2}, Iver A Langmoen^{1

2}

Affiliations

¹ Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
² Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Department of Registration, Cancer Registry of Norway, Oslo, Norway.
⁴ Department of Oncology, Oslo University Hospital, Oslo, Norway.

Abstract

Background: The survival rates in population-based series of glioblastoma (GBM) differ substantially from those reported in clinical trials. This discrepancy may be attributed to that patients recruited to trials tend to be younger with better performance status. However, the proportion and characteristics of the patients in a population considered either eligible or ineligible for trials is unknown. The generalizability of trial results is therefore also uncertain.

Methods: Using the Cancer Registry of Norway and the Brain Tumor Database at Oslo University Hospital, we tracked all patients within a well-defined geographical area with newly diagnosed GBM during the years 2012-2017. Based on data from these registries and the medical records, the patients were evaluated for trial eligibility according to criteria employed in recent phase III trials for GBM.

Results: We identified 512 patients. The median survival was 11.7 months. When we selected a potential trial population at the start of concurrent chemoradiotherapy (radiotherapy [RT]/ temozolomide [TMZ]) by the parameters age (18-70 y), passed surgery for a supratentorial GBM, Eastern Cooperative Oncology Group (ECOG) ≤2, normal hematologic, hepatic and renal function, and lack of severe comorbidity, 57% of the patients were excluded. Further filtering the patients who progressed during RT/TMZ and never completed RT/TMZ resulted in exclusion of 59% and 63% of the patients, respectively. The survival of patients potentially eligible for trials was significantly higher than of the patients not fulfilling trial eligibility criteria (P < .0001).

Conclusions: Patients considered eligible for phase III clinical trials represent a highly selected minority of patients in a real-world GBM population.

Keywords: clinical trials; eligibility; glioblastoma; selection bias; survival.