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Found 1 Presentation For Request "595P"
595P - Abdominal events in targeted therapies: Report from the Drug Rediscovery Protocol (DRUP)
- Laurien J. Zeverijn (Amsterdam, Netherlands)
Abstract
Background
Immunotherapy, kinase inhibitors and monoclonal antibodies are increasingly used in basket and/or umbrella studies for precision treatment of cancer patients. When evaluating toxicities, especially for abdominal complaints, it may be difficult to distinguish toxicity from treatment related anti-tumor effects. This may have significant impact on outcomes of these studies. Here, we present an overview of serious abdominal adverse events reported in the Drug Rediscovery Protocol (
Methods
The DRUP is an ongoing, prospective, multi-drug, pan-cancer precision oncology trial including 25 targeted agents. Eligible patients have exhausted treatments and have a molecular profile matched to targeted drugs. All SAEs leading to hospitalization, threat to life, severe disability or death during any trial phase, reported to the Independent Data Monitoring Committee were analyzed with a focus on abdominal SAEs.
Results
Between Sep 2016 and May 2020, 549 patients started treatment with one of 25 available study drugs. 103 abdominal events were reported in 71 unique patients, varying from nausea to perforation and hemorrhage. 29 events were deemed at least possibly drug-related, 31% (n=9) occurred during the first 28 days of treatment and 55% (n=16) occurred before primary study end point was met (≥ 16 weeks on treatment). In case of abdominal pain, patients had perforation (n=9), hemorrhage (n=3), progressive disease (n=6) or other causes (n=14). Differentiating between toxicity, progression or regression was especially complex for perforations, where strong anti-tumor responses (seen for immunotherapy and targeted agents) were related to perforations.
Conclusions
Abdominal side effects are a clinical challenge and often underestimated. Distinguishing a large anti-tumor effect with complications from pseudo-progression or toxicity without anti-tumor effect is difficult and has major consequences for the patient and clinical trial outcome. In the context of umbrella/basket trials with small cohorts of patients, replacement of patients due to non-evaluability has a significant impact on outcome. More structured analyses of abdominal side effects are warranted to guide clinical decision making.
Clinical trial identification
NCT02925234 (release date: 26-Aug-2016) EudraCT 2015-004398-33 (release date: 01-Oct-2015).
Legal entity responsible for the study
Governance: Stichting Het Nederlands Kanker Instituut – Antoni van Leeuwenhoek Ziekenhuis, whose registered office is at Plesmanlaan 121, 1066CX, Amsterdam, lawfully represented by R. Medema, Head of the Board representing the CPCT. Coordination and running of the study: E.E. Voest, Netherlands Cancer Institute, Division of Molecular Oncology, Amsterdam, the Netherlands.
Funding
Barcode for Life Foundation (BFL): funding; Dutch Cancer Society (KWF): funding; Hartwig Medical Foundation (HMF): sequencing; Pharmaceutical partners (Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Eisai, Ipsen, Merck, Novartis, Pfizer, Roche): funding and study drugs.
Disclosure
H. Gelderblom: Research grant/Funding (institution): FivePrime; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Debio; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Teva. H.M.W. Verheul: Honoraria (institution), Advisory/Consultancy: Glycostem; Honoraria (institution), Advisory/Consultancy: Lava Therapeutics. All other authors have declared no conflicts of interest.