July 2019: Fatal events occurring during study treatment: a pooled analysis of death cases within GBG led breast cancer trials

Data on deaths occurring during oncological clinical trials has never been systematically assessed. Therefore, we examined the incidence of death and the profile of patients who died during GBG led breast cancer trials. Information on fatal events has been prospectively captured from the trial databases and death narratives. All deaths were evaluated for possible causes, underlying conditions, treatment relatedness, time point and rate of autopsies.
Between December 1996 and January 2017, a total of 23,387 patients were treated within 32 GBG led trials. Of those 88 (0.4%) patients within 17 trials died on therapy. Baseline patients and tumor characteristics were as follows: median age was 64 [range 35-84] years; 63.2% of patients had a body mass index (BMI) ≥ 25 kg/m²; 65.9% of patients had 1 to 3 comorbidities, whereas 22.7% had 4 or more; 61.4% of the patients had 1 to 2 cardiovascular risk factors; 26.4% took more than 3 drugs; 81.7% had ECOG performance status 0; 50.0% stage III and 76.7% luminal breast cancer. The main causes of death were infection (38.6%; of those, 82.3% sepsis, 17.6% pneumonia), heart failure (14.8%), and pulmonary embolism (13.6%). The fatal events mainly occurred within the first 4 therapy cycles (55.7%), in the investigational arm (66.7%) and during anthracycline/taxane-based chemotherapy (51.1%). A relationship with the treatment was reported in 27.3% of the cases. An autopsy was performed in 13.6% of patients.
These results demonstrated that death during study treatment was mainly related to infections and happened in patients with advanced disease, high BMI, underlying comorbidities, cardiovascular risk factors and taking concomitant medications. While the identified risk factors might also apply to patients treated outside the clinical trials, it is crucial that, if considered for study participation, these patients are carefully monitored due to their higher risk of death. In particular, patients with metastatic disease need special attention being at higher risk of complications and death. Furthermore, to ensure patient’s safety, it is fundamental that investigators adhere to study protocol guidelines and promptly report SAEs and fatal events.

Furlanetto J, von Minckwitz G, Lederer B, Möbus V, Schneeweiss A, Huober J, Fasching PA, Gerber B, Bauerfeind I, Nitz U, Lück HJ, Hanusch C, Thomssen C, Untch M, Nekljudova V, Mehta K, Loibl S. Fatal events during clinical trials: an evaluation of deaths during breast cancer studies. Breast Cancer. 2019 Jun 28. [Epub ahead of print]

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