Tolerance of concurrent CDK inhibitor and radiation therapy in metastatic breast cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12598-e12598
Author(s):  
Arnaud Beddok ◽  
Alexandre Arsene-Henry ◽  
Baptiste Porte ◽  
Kim Cao ◽  
Nathaniel Scher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Metastatic Breast Cancer ◽  
Brain Lesion ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Breast Cancer Patients ◽  
Number Of Patients ◽  
Er Positive

e12598 Background: Palbociclib, a small-molecule inhibitor of cyclin-dependent kinases (CDK4 and CDK6), combined with letrozole increases progression-free survival among patients with previously untreated ER-positive, HER2 negative advanced breast cancer. The purpose of our study was to retrospectively evaluate the tolerance of the concomitant association of Palbociclib and radiation therapy (RT) at Curie Institute. Methods: Between April 2017 and August 2019, 30 women with ER-positive, HER2 negative metastatic breast cancer received locoregional (LR) and/or symptomatic irradiation at a metastatic site concurrently with Palbociclib at a daily dose of 125 mg, from d1 to d21 every 28 days. Palbociclib was always associated with endocrine therapy: letrozole (with or without an LHRH analogue) or fulvestrant. Thirty-five sites were irradiated: nine patients received post-operative locoregional RT, including the chest wall or breast and lymph node areas, and 26 sites of metastases were irradiated: 17 at the spine, 7 peripheral skeletal lesions, 1 brain lesion and 1 choroidal lesion. The dose prescribed for locoregional mammary radiotherapy was 50 Gy in 25 fractions and varied for the treatment of metastatic sites: 20 Gy in 5 fractions (n = 13), 30 Gy in 10 fractions (n = 10) and 8 Gy in 1 fraction (n = 2). The brain metastasis was stereotactically treated (1 fraction of 18 Gy). The primary endpoint was toxicity scored according to the common terminology criteria for NCI adverse events, version v5.0. Results: Mean number of days of Palbociclib during RT was 8.8 days (range, 1 to 24 days). The most common acute toxicities were dermatitis (12/35, including 2 grade 2) and neutropenia (12/35, including 9 grade 2). Palbociclib had to be stopped during the RT of two patients (2/30): one patient treated locoregionally (bilateral breast and lymph nodes irradiation) developed a grade 3 dermatitis and febrile neutropenia, another treated locoregionally developed grade 2 dysphagia. After a median follow-up since the end of RT of 17 months (6 – 31 months, SD 8), none of the patients have so far exhibited late toxicity. Conclusions: Concomitant administration of palbociclib with RT was reasonably well tolerated in our series of 30 patients. Given this experience, palbociclib should not be discontinued during radiation therapy. Nevertheless, our findings should be confirmed in prospective registration studies collecting larger number of patients.

scholarly journals Randomized phase-II evaluation of letrozole plus dasatinib in hormone receptor positive metastatic breast cancer patients

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Devchand Paul ◽  
Svetislava J. Vukelja ◽  
Frankie Ann Holmes ◽  
Joanne L. Blum ◽  
Kristi J. McIntyre ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Acquired Resistance ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Therapy Resistance ◽  
Breast Cancer Patients ◽  
Er Positive

Abstract The non-receptor tyrosine kinase Src activation plays a role in the malignant progression of breast cancer, including development of endocrine therapy resistance and survival of bone metastases. This study investigated whether adding Src kinase inhibitor dasatinib to aromatase inhibitor (AI) therapy improved outcomes in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer (MBC). Postmenopausal patients with ER-positive, HER2-negative MBC (0–1 prior chemotherapies and no prior AI for MBC) were eligible for this non-comparative, parallel group, phase-II study. Patients were randomized to letrozole (2.5 mg/day PO) alone or with dasatinib (100 mg/day PO). Patients with disease progression on letrozole alone could crossover to dasatinib plus continued letrozole. The primary endpoint was clinical-benefit-rate (CBR; complete response + partial response + stable disease ≥6 months). A total of 120 patients were randomized. The CBR of 71% (95% CI 58–83%) was observed with letrozole + dasatinib versus the projected CBR of the combination of 56%. The CBR of 66% (95% CI 52–77%) with letrozole alone also exceeded the projected CBR of 39% with letrozole alone. The CBR was 23% in the crossover arm of letrozole plus dasatinib in patients progressing on letrozole alone. Median progression-free survival with the combination was 20.1 months and 9.9 months with letrozole alone. Letrozole plus dasatinib was well tolerated, although 26% of patients required dasatinib dose reductions. In this non-comparative phase-II trial, the CBR of 71% and the median PFS of 20.1 months with letrozole + dasatinib are encouraging and suggest that dasatinib may inhibit the emergence of acquired resistance to AI therapy.

scholarly journals Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Costanza Paoletti ◽  
Meredith M. Regan ◽  
Samuel M. Niman ◽  
Emily M. Dolce ◽  
Elizabeth P. Darga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Cell Number ◽  
Rapid Progression ◽  
Breast Cancer Patients ◽  
Er Positive

AbstractCirculating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). The CTC-endocrine therapy index (CTC-ETI), consisting of CTC-ER (estrogen receptor), BCL2, human epidermal growth factor receptor (HER2), and Ki67 expression, might predict resistance to endocrine therapy (ET) in patients with ER-positive MBC. One hundred twenty-one patients with ER-positive/HER2-negative MBC initiating a new ET after ≥1 lines of ET were enrolled in a prospective, multi-institutional clinical trial. CTC-ETI and clinical/imaging follow-up were performed at baseline and serial time points. Progression-free survival (PFS) and rapid progression (RP; determined at the 3-month time point) were primary endpoints. Associations with clinical outcomes used logrank and Fisher’s exact tests. At baseline, 36% (38/107) of patients had ≥5 CTC/7.5 ml whole blood (WB). Patients with ≥5 vs. <5 CTC/7.5 ml WB had significantly worse PFS (median 3.3 vs. 5.9 months, P = 0.03). Elevated CTC at 1 month was associated with even worse PFS (1.9 vs. 5.0 months from the 1-month sample, P < 0.001). Low, intermediate, and high CTC-ETI were observed in 71 (66%), 8 (8%), and 28 (26%) patients, with median PFS of 6.9, 8.5, and 2.8 months, respectively (P = 0.008). Patients with high vs. low CTC and CTC-ETI more frequently experienced RP (CTC: 66% vs. 41%; P = 0.03; CTC-ETI: 79% vs. 40%; P = 0.002). In conclusion, CTC enumeration and the CTC-ETI assay are prognostic at baseline and follow-up in patients with ER-positive/HER2-negative MBC starting new ET. CTC at first follow-up might identify a group of patients with ER-positive MBC that could forego ET, but CTC-ETI did not contribute further.

Methallotionein expression and outcome in patients with metastatic breast cancer (MBC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1085-1085
Author(s):  
Jorge Arturo Rios-Perez ◽  
Sameem Abedin ◽  
Margaret Quinn Rosenzweig ◽  
Su Yon Jung ◽  
Rohit Bhargava ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancer Diagnosis ◽  
Rank Test ◽  
Cancer Tissue ◽  
Breast Cancer Patients ◽  
Development Of Resistance ◽  
Bivalent Metal Ions

1085 Background: Platinum-based agents are important components of therapy of metastatic breast cancer (MBC) and triple negative breast cancer. Their use can be limited by development of resistance. Metallothioneins (MT) are low molecular weight proteins believed to bind bivalent metal ions such as platinum and zinc. MT expression has been associated with decreased survival in breast cancer patients. A proposed mechanism confers resistance to platinum-based agents by their inactivation or limitation of their activity by MT binding. Methods: MT expression in 99 women with MBC (selected at random from our database of 800 women with MBC) was determined from primary breast cancer tissue (n=80) or metastatic tissue n=19). MT expression was determined by immunohistochemistry, and graded as negative, weak, moderate or strong. Clinical data was obtained through our database and supplemented by chart review. Overall survival from breast cancer diagnosis (OS), progression free survival for first metastastic regimen (PFS), and time from first metastasis to death or last update (metastatic survival, MS), were calculated through December 2011 using the log rank test. Results: Consistent with prior studies, moderate to strong MT expression was associated with decreased 5-year OS (p=.03). There was no correlation between MT expression and PFS or MS in this cohort. Surprisingly, MT expression at any degree was strongly associated with better MS in patients with MBC that received carboplatin-based regimens in the first line (n=25, p=.0005) or at any line (n=41, p=.0437). Conclusions: Consistent with prior studies, MT expression was associated with decreased survival in patients with MBC. Surprisingly, MT expression was associated with longer MS in patients with MBC that received carboplatin. These findings are inconsistent with the hypothesis that MT expression causes chemoresistance to platinum based agents in patients with metastatic breast cancer. Further studies are needed to elucidate the mechanisms behind these findings.

scholarly journals Efficacy and Safety of Eribulin in Taxane-Refractory Patients in the “Real World”

2016 ◽  
Author(s):  
Vito Lorusso ◽  
Saverio Cinieri ◽  
Agnese Latorre ◽  
Luca Porcu ◽  
Lucia Del Mastro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Peripheral Neurotoxicity ◽  
Eribulin Mesylate ◽  
Free Survival ◽  
Toxic Drugs

Taxanes have been shown to be the most effective treatment for recurrent or metastatic breast cancer. However, for patients pretreated with taxanes, more active and possibly less toxic drugs are needed. In this retrospective study, we investigated on the effectiveness and safety of eribulin mesylate in 91 taxane-refractory subjects, extracted from the ESEMPIO database, which included 497 metastatic breast cancer patients treated with eribulin allover the Italy. This analysis included only those patients who have shown disease progression while receiving taxane therapy (primary refractory), or those who achieved a response followed by progression while still on therapy (taxane failure). Overall, 41/91 patients (45.2%) showed a clinical benefit; 1 complete response (2.2%) and 16 partial responses (17.6%) were observed. The median progression free survival was 3.1 months (95% CI: 2.8&ndash;3.5) and the median overall survival was 11.6 months (95% CI: 8.7&ndash;16.7). With regard to toxicity, 53 patients (58%) experienced asthenia/fatigue, 23 (25%) showed peripheral neurotoxicity, 18 (20%) alopecia, 12 (13%) mild constipation and 27 (30%) neutropenia. The toxicity related to the treatment led to eribulin dose reduction in 19 (21%) and discontinuation in 9 (10%) patients, respectively. In conclusion, this study suggests that eribulin is effective and well tolerated also in taxane-refractory patient.

scholarly journals COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area

2020 ◽  
Author(s):  
Perrine Vuagnat ◽  
Maxime Frelaut ◽  
Toulsie Ramtohul ◽  
Clémence Basse ◽  
Sarah Diakite ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Intensive Care Unit ◽  
Radiation Therapy ◽  
Intensive Care ◽  
Metastatic Breast Cancer ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Paris Area

AbstractBackgroundCancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France).MethodsAn IRB-approved prospective registry was set up at ICH for all breast cancer patients with COVID-19 symptoms or radiologic signs.ResultsAmong 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (>70) were the two factors associated with a higher risk of intensive care unit admission and/or death.ConclusionsThis prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe SARS-CoV-2 infection in breast cancer patients.

scholarly journals Randomized Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy: Results of PrE0102

2018 ◽  
Vol 36 (16) ◽  
pp. 1556-1563 ◽  
Author(s):  
Noah Kornblum ◽  
Fengmin Zhao ◽  
Judith Manola ◽  
Paula Klein ◽  
Bhuvaneswari Ramaswamy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival ◽  
Er Positive ◽  
Epidermal Growth

Purpose The mammalian target of rapamycin inhibitor everolimus targets aberrant signaling through the PI3K/AKT/mammalian target of rapamycin pathway, a mechanism of resistance to anti-estrogen therapy in estrogen receptor (ER)–positive breast cancer. We hypothesized that everolimus plus the selective ER downregulator fulvestrant would be more efficacious than fulvestrant alone in ER-positive metastatic breast cancer resistant to aromatase inhibitor (AI) therapy. Patients and Methods This randomized, double-blind, placebo-controlled, phase II study included 131 postmenopausal women with ER-positive, human epidermal growth factor receptor 2–negative, AI-resistant metastatic breast cancer randomly assigned to fulvestrant (500 mg days 1 and 15 of cycle 1, then day 1 of cycles 2 and beyond) plus everolimus or placebo. The study was designed to have 90% power to detect a 70% improvement in median progression-free survival from 5.4 months to 9.2 months. Secondary end points included objective response and clinical benefit rate (response or stable disease for at least 24 weeks). Prophylactic corticosteroid mouth rinses were not used. Results The addition of everolimus to fulvestrant improved the median progression-free survival from 5.1 to 10.3 months (hazard ratio, 0.61 [95% CI, 0.40 to 0.92]; stratified log-rank P = .02), indicating that the primary trial end point was met. Objective response rates were similar (18.2% v 12.3%; P = .47), but the clinical benefit rate was significantly higher in the everolimus arm (63.6% v 41.5%; P = .01). Adverse events of all grades occurred more often in the everolimus arm, including oral mucositis (53% v 12%), fatigue (42% v 22%), rash (38% v 5%), anemia (31% v. 6%), diarrhea (23% v 8%), hyperglycemia (19% v 5%), hypertriglyceridemia (17% v 3%), and pneumonitis (17% v 0%), although grade 3 to 4 events were uncommon. Conclusion Everolimus enhances the efficacy of fulvestrant in AI-resistant, ER-positive metastatic breast cancer.

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