The past 10 years have seen a rise in clinical trials for the treatment of primary and recurrent glioblastoma—but the “slightly positive trend” has been due to an increase in phase 2, not phase 3, studies, say researchers from University of Bern in Switzerland. Moreover, the majority of these trials focus on drugs designed for central nervous system (CNS) malignancies; trials addressing radiotherapy, surgery, imaging, and other therapeutic or diagnostic methods “appear to be rare.”
The researchers analyzed records of 208,777 studies registered at ClinicalTrials.gov. They classified trials according to disease setting (newly diagnosed glioblastoma, recurrent disease, and no differentiation) and by intervention (standard or experimental). All surgical approaches were considered experimental as were all radiotherapy approaches in the recurrent setting.
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Nearly all the trials (91%) evaluated forms of systemic therapy, with 44% in primary and 54% in recurrent disease. The majority of trials were phase 2 studies (88%); only 11% were phase 3.
Researchers identified 100 different molecular agents or biologics of which 40 had initially been approved for indications other than glioblastoma or CNS malignancies. Two agents (carmustine and lomustine) were approved for glioblastoma or other CNS or solid malignancies. Only 1 (temozolomide) was approved for glioblastoma. Of 57 compounds with investigational status, 19 were developed specifically for glioblastoma.
By contrast, the researchers say that surgery, radiotherapy, and imaging are “heavily underrepresented,” being the focus of > 10% of all phase 1 and 2 glioblastoma trials.
Industry “has displayed a strong interest in sponsoring trials for glioblastoma,” the researchers note. The fact that industry was a primary sponsor of one-fourth of the trials and a leading source of monetary support in 44% “indicates that glioblastoma is an attractive target even financially.” But the authors find “reason for concern” in the lack of industrial funding for research beyond forms of systemic therapy.
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They suggest, for instance, that learning more about alternative radiotherapy schedules along with dose or volume alterations could be of interest for glioblastoma treatment. They also note that imaging modalities rarely are evaluated in the prospective setting, and the size and role of the optimal radiotherapy margins are “a matter of debate”—of particular importance in recurrent glioblastoma.
The most probable cause for the upward trend of phase 2 trials in glioblastoma, the researchers say, is the failure of previous early investigative treatments to show a clinically significant advantage. Instead of starting more trials “unselectively,” they suggest, it might be better to enroll patients with glioblastoma in early phase trials with novel designs.
Source:
Cihoric N, Tsikkinis A, Minniti G, et al. Radiat Oncol. 2017;12(1):1.
doi: 10.1186/s13014-016-0740-5.
