ABSTRACT
BACKGROUND: Until recently, treatment options for patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) and resistance to endocrine therapy were limited to chemotherapy. This real-world study describes treatment patterns and outcomes in patients treated with chemotherapy in the United States before approval of antibody-drug conjugates. PATIENTS AND METHODS: This retrospective, observational study included adults with HR+/HER2- mBC from the ConcertAI Patient360™ Breast Cancer dataset who initiated their first chemotherapy in the metastatic setting between January 2011 and June 2021. Treatment patterns were described; real-world overall survival, time to next treatment or death, and real-world progression-free survival were evaluated for all eligible patients and patients treated with subsequent chemotherapy. Index dates were the start date of each chemotherapy treatment. RESULTS: Among 1545 eligible patients, 76% were white, 12% had Eastern Cooperative Oncology Group performance status ≥2, 38% had de novo mBC, and median age was 61 years (range, 52-69 years). Within the index period, capecitabine was used the most as the first chemotherapy agent and decreased in later treatments, while the use of eribulin increased between first and fourth chemotherapies. Median (95% confidence interval) real-world overall survival was 23.3 months (21.3-25.4 months) from start of first chemotherapy, time to next treatment or death was 6.5 months (5.9-7.1 months), and real-world progression-free survival was 6.9 months (6.4-7.6 months); median times from second, third, and fourth chemotherapies decreased with each additional chemotherapy treatment. CONCLUSIONS: This real-world study demonstrates that for patients with HR+/HER2- mBC, chemotherapy provides relatively limited survival benefit which decreases with each additional chemotherapy line, and highlights the need for improved treatment options.
ABSTRACT
BACKGROUND: Inhaled cyclosporine (CsA) is being investigated as a prophylaxis for lung transplant rejection. Lung deposition and systemic exposure of nebulized CsA in lung transplant patients was evaluated as part of the Phase 3 cyclosporine inhalation solution (CIS) trial (CYCLIST). METHODS: Ten patients received 300 mg of CIS (62.5 mg/mL CsA in propylene glycol) admixed with 148 MBq of Tc-DTPA (technetium-99m bound to diethylenetriaminepentaacetic acid) administered using a Sidestream(®) disposable jet nebulizer. Deposition was assessed using a dual-headed gamma camera. Blood samples were collected over a 24-hr time period after aerosol dosing and analyzed for CsA levels. A pharmacokinetic analysis of the resulting blood concentration versus time profiles was performed. RESULTS: The average total deposited dose was 53.7 ± 12.7 mg. Average pulmonary dose was 31.8 ± 16.3 mg, and stomach dose averaged 15.5 ± 11.1 mg. Device performance was consistent, with breathing maneuvers influencing dose variation. Predose coaching with five of 10 patients reduced stomach deposition (22.6 ± 11.2 vs. 8.3 ± 5.2 mg; p=0.03). Blood concentrations declined quickly from a maximum of 372 ± 140 ng/mL to 15.3 ± 9.7 ng/mL at 24 hr post dose. Levels of AUC(0-24) [area under the concentration vs. time curve from 0 to 24 hr] averaged 1,493 ± 746 ng hr/mL. On a three times per week dose regimen, this represents <5% of the weekly systemic exposure of twice per day oral administration. CONCLUSIONS: Substantial doses of CsA can be delivered to the lungs of lung transplant patients by inhaled aerosol. Systemic levels are small relative to typical oral CsA administration.