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.

scholarly journals Systemic immunity markers associated with lymphocytes predict the survival benefit from paclitaxel plus bevacizumab in HER2 negative advanced breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shogo Nakamoto ◽  
Masahiko Ikeda ◽  
Shinichiro Kubo ◽  
Mari Yamamoto ◽  
Tetsumasa Yamashita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Multivariable Analysis ◽  
Absolute Lymphocyte Count ◽  
Predictive Markers ◽  
Advanced Breast ◽  
Chemotherapeutic Regimen ◽  
Systemic Immunity ◽  
Lymphocyte Ratio ◽  
Lymphocyte To Monocyte Ratio

AbstractAlthough paclitaxel plus bevacizumab (PB) therapy is an effective chemotherapeutic regimen for HER2-negative advanced breast cancer (ABC), predictive markers for its effectiveness remain undefined. We investigated the usefulness of systemic immunity markers associated with lymphocytes as predictive markers for PB therapy in patients with HER2-negative ABC. We retrospectively reviewed data from 114 patients with HER2-negative ABC who underwent PB therapy from November 2011 to December 2019. We calculated the absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) as representative systemic immunity markers. The time to treatment failure (TTF) and overall survival (OS) of the patients with high ALC, low NLR, and high LMR were significantly longer compared with those of the patients with low ALC, high NLR, and low LMR. A multivariable analysis revealed that high ALC, low NLR, and low PLR were independent predictors for TTF and high ALC, low NLR, and high LMR were independent predictors for OS. Systemic immunity markers were significantly associated with longer TTF and OS in patients who underwent PB therapy and may represent predictive markers for PB therapy in patients with HER2-negative 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.

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.

Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate.

1998 ◽  
Vol 16 (2) ◽  
pp. 453-461 ◽  
Author(s):  
P Dombernowsky ◽  
I Smith ◽  
G Falkson ◽  
R Leonard ◽  
L Panasci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Objective Response ◽  
Advanced Breast ◽  
Megestrol Acetate ◽  
Dose Effect ◽  
Double Blind ◽  
Once Daily ◽  
Previously Treated

PURPOSE To compare two doses of letrozole and megestrol acetate (MA) as second-line therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens. PATIENTS AND METHODS Five hundred fifty-one patients with locally advanced, locoregionally recurrent or metastatic breast cancer were randomly assigned to receive letrozole 2.5 mg (n = 174), letrozole 0.5 mg (n = 188), or MA 160 mg (n = 189) once daily in a double-blind, multicenter trial. Data were analyzed for tumor response and safety variables up to 33 months of follow-up evaluation and for survival up to 45 months. RESULTS Letrozole 2.5 mg produced a significantly higher overall objective response rate (24%) compared with MA (16%; logistic regression, P = .04) or letrozole 0.5 mg (13%; P = .004). Duration of objective response was significantly longer for letrozole 2.5 mg compared with MA (Cox regression, P = .02). Letrozole 2.5 mg was significantly superior to MA and letrozole 0.5 mg in time to treatment failure (P = .04 and P = .002, respectively). For time to progression, letrozole 2.5 mg was superior to letrozole 0.5 mg (P = .02), but not to MA (P = .07). There was a significant dose effect in overall survival in favor of letrozole 2.5 mg (P = .03) compared with letrozole 0.5 mg. Letrozole was significantly better tolerated than MA with respect to serious adverse experiences, discontinuation due to poor tolerability, cardiovascular side effects, and weight gain. CONCLUSION The data show letrozole 2.5 mg once daily to be more effective and better tolerated than MA in the treatment of postmenopausal women with advanced breast cancer previously treated with antiestrogens.

Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer.

1995 ◽  
Vol 13 (11) ◽  
pp. 2722-2730 ◽  
Author(s):  
B L Weber ◽  
C Vogel ◽  
S Jones ◽  
H Harvey ◽  
L Hutchins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Advanced Breast ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

PURPOSE We evaluated single-agent intravenous (IV) vinorelbine as first- and second-line treatment for advanced breast cancer (ABC) in patients who were not resistant to anthracyclines. Objective tumor response (TR) and toxicity were assessed. PATIENTS AND METHODS A total of 107 women were enrolled onto this multicenter, nonrandomized, open-label phase II study. Patients were stratified into first- and second-line treatment groups, based on prior treatment history. Vinorelbine was initially given at 30 mg/m2/wk, with dose modification for toxicity as indicated. Therapy was continued until disease progression or severe toxicity mandated withdrawal or until the patient asked to be removed from the study. RESULTS The objective response rate for all patients was 34% (95% confidence interval [CI], 25% to 44%): 35% (95% CI, 23% to 48%) for first-line patients and 32% (95% CI, 20% to 47%) for second-line patients. Nine first-line and three second-line patients obtained a complete response (CR). The median duration of objective response was 34 weeks in both groups. The overall survival durations of first- and second-line patients were 67 weeks and 62 weeks, respectively. Granulocytopenia was the predominant dose-limiting toxicity. Two patients died on study as a result of granulocytopenic sepsis. CONCLUSION Single-agent vinorelbine is an effective and well-tolerated agent for first- and second-line therapy of ABC. The results of this study confirm the findings of similar international trials and suggest vinorelbine should be considered a valid treatment option for patients with ABC and a potential component in future combination regimens for this disease.

Multicenter phase II efficacy trial of toremifene in tamoxifen-refractory patients with advanced breast cancer.

1993 ◽  
Vol 11 (2) ◽  
pp. 345-350 ◽  
Author(s):  
C L Vogel ◽  
I Shemano ◽  
J Schoenfelder ◽  
R A Gams ◽  
M R Green
Keyword(s):  
Breast Cancer ◽  
Treatment Failure ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Objective Response ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Cross Resistance ◽  
High Dose

PURPOSE To explore further the efficacy of high-dose toremifene in patients with advanced breast cancer who had failed to respond to tamoxifen or whose disease had progressed on tamoxifen. PATIENTS AND METHODS One hundred two perimenopausal or postmenopausal women with metastatic breast cancer refractory to tamoxifen were entered onto a phase II clinical trial of toremifene at a dose of 200 mg/d. The study patients consisted of 28 primarily refractory patients; 43 patients who had relapsed after a prior tamoxifen response; and 31 patients who had relapsed while receiving adjuvant tamoxifen. This was a heavily pretreated group of patients, with 65% having failed chemotherapeutic attempts and 72% having failed two or more hormonal therapies. Forty-nine percent of patients had visceral dominant disease. RESULTS The objective response rate was 5% (95% confidence interval [CI], 3% to 7%). The median time to treatment failure (TTF) was 10.9 months for the five responders. An additional 23% of patients had stable disease for a median TTF of 7.8 months, whereas the patients who experienced treatment failure had a median TTF of 2.1 months. Whether those patients with stable disease derived clinical benefit or simply had slow progression in an intrinsically indolent disease presentation is uncertain. Common toxicities were generally mild and similar to those encountered with tamoxifen. CONCLUSION We conclude that there is major cross-resistance between tamoxifen and toremifene and that only occasional tamoxifen-refractory patients will have objective responses to toremifene.

Sign in / Sign up

Export Citation Format

Share Document