Found 2 Presentations For Request "50P"
150P - Eligibility of real-world patients with metastatic breast cancer in clinical trials
- Atul Batra (New Delhi, Delhi, India)
- Atul Batra (New Delhi, Delhi, India)
- Shiying Kong (Calgary, Canada)
- Rodrigo Rigo (Calgary, Canada)
- Winson Cheung (Calgary, Canada)
Abstract
Background
The results of clinical trials in metastatic breast cancer (MBC) are often generalized to real-world patients. However, clinical trials have stringent inclusion and exclusion criteria, which can potentially lead to poor generalizability of results and slow accrual. This study was conducted to determine the proportion of real-world patients with MBC who would be eligible for clinical trials based on common eligibility criteria and to compare outcomes in eligible and ineligible patients.
Methods
Patients diagnosed with MBC in 2004-2015 from the Alberta cancer registry were included. Patients with one of the following criteria were deemed ineligible: age >75 years, comorbid conditions (uncontrolled diabetes, heart disease, liver disease, and kidney disease), anemia, and history of immunosuppression or a prior malignancy. The likelihood of receiving any therapy was analyzed using logistic regression and factors affecting overall survival (OS) were assessed by Cox model.
Results
A total of 1585 patients with MBC were identified with median age at diagnosis was 63 years (interquartile range: 53-75 years). Approximately 44% (693) patients were deemed trial-ineligible and the most common reasons for ineligibility were advanced age (24%), renal dysfunction (17%), and cardiac disease (8%), respectively. In the real-world, 87% of eligible patients received hormonal or chemotherapy as compared to 72% of ineligible patients [odds ratio 2.65; 95% confidence interval, 2.04-3.42; P< 0.0001]. The 5-year OS of trial-ineligible patients who received any therapy was significantly better than those who did not (Table).
Group 5-year OS Hazard ratio 95% CI P-value Ineligible and no therapy (n=195) 2.1% -- -- -- Ineligible and received therapy (n=498) 24.7% 0.75 0.59-0.96 0.02 Eligible (n=892) 34.8% 0.69 0.53-0.9 0.006
Conclusions
Despite being ineligible for clinical trials by the common eligibility criteria, most of the patients still derive benefit from treatment. Relaxation of an arbitrary upper limit of age as an inclusion criteria for clinical trials is likely to enhance the representation of real-world patients leading to faster accrual and increase in generalizability of results of such trials.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
50P - Cardiosafe nano-formulation of doxorubicin allows coadministration with trastuzumab in neoadjuvant setting improving antitumor efficacy and preventing trastuzumab-mediated cardiotoxicity in HER2 + murine model of breast cancer
- Serena Mazzucchelli (Milan, Italy)
- Serena Mazzucchelli (Milan, Italy)
- Francesco Andreata (Milan, Italy)
- Arianna Bonizzi (Milan, Italy)
- Marta Sevieri (Milan, Italy)
- Marta Truffi (Milan, Italy)
- Leopoldo Sitia (Milan, Italy)
- Roberta Ottria (Milan, Italy)
- Filippo Silva (Milan, Italy)
- Pietro F. Zerbi (Milan, Italy)
- Davide Prosperi (Milano, Italy)
- Fabio Corsi (Milan, Italy)
Abstract
Background
The mainstay of neoadjuvant chemotherapy for HER2-positive breast cancer (BC) is the combination of highly cytotoxic drugs such as doxorubicin (DOX) and the anti-HER2 therapy with Trastuzumab (TZ), which allows a pathological complete response in up to 50% of patients. Unfortunally, their co-administration is strongly limited by intrinsic cardiotoxicity, therefore only a sequential administration of DOX and TZ is allowed in clinical practice. However, the concurrent use of DOX and TZ has been demonstrated to be more useful both for responder and non-responder patients representing an unmet clinical need in BC oncology. Nanomedicine could fix this issue developing smart drug delivery systems specifically targeted toward BC cells, which display limited off-target toxicity. Here, we propose nanoformulation of DOX in H-Ferritin-nanocages (HFn-DOX), exploiting its capability to increase doxorubicin (DOX) anticancer efficacy while reducing its cardiotoxicity.
Methods
A murine model of HER2+ BC has been treated twice a week for 2 weeks and half with placebo, TZ alone (5 mg/Kg), DOX or HFn-DOX (1 mg/Kg), DOX+TZ and HFn-DOX+TZ. Tumors have been evaluated for size, apoptosis grade, Granzyme release, angiogenesis, Tumor Infiltrating Leucocytes enumeration, amount of Cancer-Associated Fibroblasts, DOX and DOXol content, TZ accumulation and penetration using different approaches such as immunohistochemistry, western blot, flow cytometry, immunofluorescence and mass spectrometry. Cardiotoxicity has been evaluated by morphological analysis of cardiac tissue by transmission electron microscopy. TZ accumulation has been assessed also in heart lysates by western blot.
Results
The coadministration of HFn-DOX with TZ displays increased antitumor potential combined with a cardio protective effect against TZ-induced mitochondrial cardiotoxicity, which is attributable to its capability to reduce TZ accumulation in heart improving in the meantime its penetration in tumour.
Conclusions
HFn-DOX could be a valuable strategy to allow safe co-administration of DOX and TZ exploitable for clinical application.
Legal entity responsible for the study
The authors.
Funding
Regione Lombardia and Fondazione Cariplo (grant number 2016-0919).
Disclosure
All authors have declared no conflicts of interest.