Pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate in advanced breast cancer patients.

1992 ◽  
Vol 10 (7) ◽  
pp. 1176-1182 ◽  
Author(s):  
M C Etienne ◽  
G Milano ◽  
M Frenay ◽  
N Renee ◽  
E Francois ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Advanced Breast Cancer ◽  
Medroxyprogesterone Acetate ◽  
Objective Response ◽  
Plasma Concentrations ◽  
Advanced Breast ◽  
Response To Treatment ◽  
Prolonged Treatment ◽  
Therapeutic Window

PURPOSE Medroxyprogesterone acetate (MPA) is one of the major drugs used in endocrine therapy for advanced breast cancer. However, its optimal dose still has not been clearly established. Response to treatment and drug-related side effects were analyzed as a function of plasma MPA concentrations during prolonged MPA treatment. PATIENTS AND METHODS MPA plasma concentrations were measured (high-performance liquid chromatography [HPLC] assay) at steady state (Css min) in 129 patients (mean age, 63 years; range, 34 to 87) treated by MPA (86% were treated orally exclusively with daily doses ranging from 400 to 2,000 mg). RESULTS A wide interpatient variability was noted in MPA Css min for the 70 patients who received 1,000 mg/d orally (median, 51 ng/mL; range, 10 to 269 ng/mL). Intrapatient analysis of the evolution of MPA Css min during prolonged treatment showed relative stability of MPA concentrations (mean CV, 20.6%). A weak but significant correlation was demonstrated between oral doses and MPA Css min (P = .016). Thirty-five percent of patients (45 of 129) developed MPA-related side effects that were associated with the highest plasma MPA concentrations; medians were 81 and 32 ng/mL for toxic and nontoxic treatments, respectively (P less than .001). Objective response was assessable in 55 patients who were treated by MPA exclusively. Plasma MPA concentrations were significantly different (P = .025) between patients with progressive disease (PD) (median, 46 ng/mL) and those with complete response (CR), partial response (PR), or stable disease (SD) (median 65 ng/mL). Comparison of CR plus PR versus SD versus PD showed only a tendency toward significant differences in MPA Css min (P = .07). Analysis of toxicity and response as a function of the oral dose did not show any significant relationship. These data suggested an optimal therapeutic window for MPA Css min located within 50 to 70 ng/mL. CONCLUSION This study demonstrates that plasma MPA concentration, as opposed to the administered dose, is a determining factor for toxicity and response therapy [corrected].

scholarly journals Patient Preferences: Results of a German Adaptive Choice-Based Conjoint Analysis (Market Research Study Sponsored by Eli Lilly and Company) in Patients on Palliative Treatment for Advanced Breast Cancer

Breast Care ◽  
2021 ◽  
pp. 1-9
Author(s):  
Mattea Reinisch ◽  
Norbert Marschner ◽  
Thorsten Otto ◽  
Agnieszka Korfel ◽  
Clemens Stoffregen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Advanced Breast Cancer ◽  
Patient Preferences ◽  
Advanced Breast ◽  
Line Treatment ◽  
Second Line ◽  
Quantitative Survey ◽  
Therapy Assessment ◽  
Adaptive Choice

<b><i>Introduction:</i></b> Integration of patient preferences into shared decision making improves disease-related outcomes, but such data from patients with advanced breast cancer (aBC) are limited. The objective of this study was to demonstrate the relative importance of overall survival (OS) and progression-free survival (PFS) in relation to quality of life (QoL) and therapy-associated side effects from the perspective of patients with aBC. <b><i>Methods:</i></b> Postmenopausal patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative aBC receiving first- or second-line treatment were recruited throughout Germany. Patient-relevant attributes for aBC therapy assessment were collected using a stepwise multimodal approach. A conjoint matrix was developed, resulting in 2 attributes for therapy goals (OS and PFS), 4 for QoL, and 6 for side effects. An online quantitative survey was then performed using adaptive choice-based conjoint (ACBC) methodology. <b><i>Results:</i></b> The quantitative survey included 104 patients: 67 (64.4%) receiving first-line treatment and 37 (35.6%) receiving second-line treatment. The QoL attribute “physical agility and mobility” received the highest utility score (19.4 of 100%), reflecting the greatest importance to patients, followed by treatment goals (OS [15.2%] and PFS [14.4%]). Therapy-related side effects were less important, with nausea/vomiting being the most important (9.3%), followed by infection (6.4%) and hair loss (5.0%). The McFadden pseudo <i>R</i><sup>2</sup> (0.805), the root likelihood (0.864), and the χ<sup>2</sup> test (2,809.041; <i>p</i> &#x3c; 0.0001) indicated a very good fit of the statistical model. <b><i>Conclusion:</i></b> Using ACBC analysis, it appears that QoL, OS, and PFS are most important to postmenopausal patients with aBC in relation to cancer treatment. Side effects seem to be less important if OS or PFS are prolonged and the QoL is maintained. Thus, QoL, OS, and PFS should be considered equally when making treatment decisions in aBC.

scholarly journals Abemaciclib as initial therapy for advanced breast cancer: MONARCH 3 updated results in prognostic subgroups

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Stephen Johnston ◽  
Joyce O’Shaughnessy ◽  
Miguel Martin ◽  
Jens Huober ◽  
Masakazu Toi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Liver Metastases ◽  
Advanced Breast Cancer ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Breast ◽  
Treatment Benefit ◽  
Significant Treatment

AbstractIn MONARCH 3, continuous dosing of abemaciclib with an aromatase inhibitor (AI) conferred significant clinical benefit to postmenopausal women with HR+, HER2− advanced breast cancer. We report data for clinically prognostic subgroups: liver metastases, progesterone receptor status, tumor grade, bone-only disease, ECOG performance status, and treatment-free interval (TFI) from an additional 12-month follow-up (after final progression-free survival [PFS] readout). In the intent-to-treat population, after median follow-up of approximately 39 months, the updated PFS was 28.2 versus 14.8 months (hazard ratio [HR], 0.525; 95% confidence interval, 0.415–0.665) in abemaciclib versus placebo arms, respectively. Time to chemotherapy (HR, 0.513), time to second disease progression (HR, 0.637), and duration of response (HR, 0.466) were also statistically significantly prolonged with the addition of abemaciclib to AI. Treatment benefit was observed across all subgroups, as evidenced by objective response rate change from the addition of abemaciclib to AI, with the largest effects observed in patients with liver metastases, progesterone receptor-negative tumors, high-grade tumors, or TFI < 36 months. Extended follow-up in the MONARCH 3 trial further confirmed that the addition of abemaciclib to AI conferred significant treatment benefit to all subgroups, including those with poorer prognosis.

scholarly journals Pembrolizumab Plus Gemcitabine in the Subset of Triple-Negative Advanced Breast Cancer Patients in the GEICAM/2015-04 (PANGEA-Breast) Study

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5432
Author(s):  
Luis de la Cruz-Merino ◽  
María Gion ◽  
Josefina Cruz-Jurado ◽  
Vanesa Quiroga ◽  
Raquel Andrés ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Treatment Efficacy ◽  
Triple Negative ◽  
Objective Response ◽  
Suppressor Cells ◽  
Primary Objective ◽  
Advanced Breast ◽  
Breast Cancer Patients

The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon’s design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months.

Alpelisib and fulvestrant efficacy in HR-positive HER2-negative PIK3CA-mutant advanced breast cancer: Data from the French early access program.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1064-1064
Author(s):  
Diana Bello ◽  
Alexandre Bertucci ◽  
Thibault De La Motte Rouge ◽  
Cyriac Blonz ◽  
Sarra Akla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Advanced Breast ◽  
Prior Treatment ◽  
Cancer Data ◽  
Early Access ◽  
Systemic Treatments ◽  
Access Program

1064 Background: In 11.2018, the PIK3CA-inhibitor alpelisib was made available in France through an early access program (EAP), in combination with fulvestrant in pre-treated PIK3CA-mutant, HR-positive, HER2-negative advanced breast cancer (ABC) patients. Patients had to received two or more prior systemic treatments for ABC, including an aromatase inhibitor and a CDK4/6 inhibitor in the absence of contraindications. This retrospective real-life, EAP-based study aimed to assess the efficacy and safety of alpelisib/fulvestrant combination in the post CDK4/6 inhibitor setting. Methods: The IRB-approved protocol and call for data were sent on 10.2020 to the cancer centers which participated the most in the EAP prospective registry. Eligible patients were women who started alpelisib/fulvestrant between 11. 2018 and 10.2020 as part of the EAP (which excluded patients with visceral crisis or inflammatory BC). Alpelisib and fulvestrant were used at standard doses. Primary endpoint was PFS by local investigators using RECIST1.1. Secondary endpoints included objective response rate and safety (NCI CTCAE v5.0). Results: 10 centers provided individual data regarding 209 consecutive patients. Patients had received a median number of 4 (1-14) previous systemic treatments for ABC, including CDK4/6 inhibitors, chemotherapy, fulvestrant (alone or in combination) and everolimus for 206 (98.8%), 159 (76.1%), 163 (78%) and 123 (58.8%) patients, respectively. With a median FU of 7.0 months, median PFS was 4.0 months (95%CI [3.5;5.0]) and 35.4% of 164 evaluable patients had an objective response. After stratification on the number of prior lines of treatment, prior exposure to everolimus had no impact on PFS (mPFS in the 123 patients pretreated with everolimus: 4.0m, 95%CI [3.5-5.5]). Of note, this population was enriched in patients who had a long disease control by everolimus (median time spent on everolimus: 7.0m, range (6.5-9.0)). In multivariable analysis, characteristics significantly associated with longer PFS were PS < 3 (HR = 0.03, 95%CI [0.02-0.29]) and prior treatment with fulvestrant (HR = 0.53, 95%CI [0.32-0.89]). N = 81(38.8%) patients discontinued alpelisib due to adverse events (AEs). Most frequent grade 3/4 AEs were hyperglycemia, skin rash, diarrhea and fatigue occurring in 13.4, 8.1, 4.8 and 1.9 % of patients, respectively. Conclusions: Despite heavy pre-treatments, alpelisib +fulvestrant had a clinically relevant efficacy in the French EAP population. Interestingly, prior treatment with either everolimus or fulvestrant did not overtly impair alpelisib-fulvestrant efficacy. The best treatment sequence for PI3KCA/mTOR inhibitors could be examined in future trials in PIK3CA-mutant ER+/HER2- ABC patients.

Cisplatin and VP16 in Metastatic Breast Carcinoma as a Third-Line Chemotherapy: A Randomized Study Comparing Low versus High Doses of Cisplatin

1995 ◽  
Vol 81 (4) ◽  
pp. 241-244 ◽  
Author(s):  
Guido Ceci ◽  
Giancarlo Bisagni ◽  
Giorgio Cocconi ◽  
Carmelina Rodinò ◽  
Virginio Belsanti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Low Dose ◽  
Objective Response ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
High Dose ◽  
Severe Toxicity ◽  
Third Line ◽  
Line Chemotherapy

Aims and background The study was designed to define the activity of the combination of cisplatin and etoposide as third-line chemotherapy for advanced breast cancer and to investigate the role of the dosage of cisplatin on the effectiveness of the combination. Methods Ninety-five eligible patients with advanced breast cancer who had failed or relapsed on two previous lines of chemotherapy were randomized to receive cisplatin at a high dose (100 mg/m2 i.v. day 1, arm A) or a low dose (60 mg/m2 day 1, arm B), combined with etoposide (100 mg/m2 i.v. days 4, 6 and 8). Cycles were repeated every 3 weeks. Results Of the 78 patients evaluable for response (39 in arm A and 39 in arm B), 9 (12%) showed complete or partial response, 5 (13%) in the high-dose arm and 4 (10%) in the low-dose arm. One complete response was seen in the high-dose arm and none in the low-dose arm. The only 2 patients with brain involvement showed an objective response (one CR in arm A and one PR in arm B). Median time to progression was 14 weeks in arm A and 10 weeks in arm B, median duration of remission 28 and 34 weeks, and survival 36 and 35 weeks, respectively. The differences were not significant. As expected, the patients in the high-dose arm experienced more severe toxicity. One toxic death was observed in each arm due to sepsis in agranulocytosis. The difference was statistically significant regarding nausea and vomiting. Neurotoxicity and ototoxicity were not relevant problems in this patient setting. Conclusions Considering the very poor prognostic factors presented by these patients, the combination showed a certain activity, and further evaluation in earlier stages of disease is warranted. A particular responsiveness on brain metastases is suggested. The dose of cisplatin was not proven to be of significant importance.

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