Clinical outcomes of patients with metastatic breast cancer enrolled in phase I clinical trials

2021 ◽  
Vol 157 ◽  
pp. 40-49
Author(s):  
Carmen Criscitiello ◽  
Antonio Marra ◽  
Stefania Morganti ◽  
Paola Zagami ◽  
Sara Gandini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Clinical Outcomes ◽  
Metastatic Breast ◽  
Phase I Clinical Trials

Patients with metastatic breast cancer enrolled in phase I clinical trials: Clinical outcomes and cohort trends.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1099-1099
Author(s):  
Jennifer Weiss ◽  
Dexiang Gao ◽  
Anthony D. Elias ◽  
Virginia F. Borges ◽  
Peter Kabos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Clinical Outcomes ◽  
Clinical Benefit ◽  
Metastatic Breast ◽  
Cancer Center ◽  
Phase I Clinical Trials ◽  
Metastatic Setting

1099 Background: Phase I clinical trials have traditionally enrolled patients with advanced solid tumors and many providers perceive the likelihood of clinical benefit as low. The purpose of this study was to evaluate clinical outcomes for patients with metastatic breast cancer enrolled on Phase I clinical trials and explore differences in outcomes for patients enrolled in all-comer versus breast cancer-specific cohorts. Methods: We performed a retrospective chart review of patients with metastatic breast cancer enrolled in Phase I clinical trials at the University of Colorado Cancer Center from 2012-2018. We included trials with Phase I and/or Phase Ib in the title. Studies or cohorts enrolling patients with ≥ 3 tumor types were considered all-comer and those with enrollment restricted to breast cancer or a breast cancer subtype were considered breast cancer-specific. Results: A total of 208 patients were enrolled in Phase I clinical trials, 168 in breast cancer-specific cohorts and 40 in all-comer trials. Patients on average were 56.9 years old (range 31-79), 98.6% (205/208) female, 1.4% (3/208) male, 57.2% ER+/Her2-, 30.1% ER-/Her2- and 11.1% Her2+. Patients received on average 2.1(range 0-10) prior lines of chemotherapy in the metastatic setting. Patients enrolled on Phase I clinical trials remained on study without progression on average for 138 days (CI 95%, 112.64 to 163.91). Patients enrolled on breast cancer-specific studies remained on study for 152 days (CI 95%, 120.66 to 182.56) compared to 82 days (CI 95%, 59.43 to 105.13) for those enrolled on all-comer trials, p< 0.05. Patients went off study for disease progression (83.17%), adverse events (7.69%), and other (9.14%), including withdrawal of consent. Conclusions: Patients with metastatic breast cancer previously treated with multiple lines of chemotherapy in the metastatic setting enrolled in Phase I clinical trials received clinical benefit from treatment that is favorable compared to historical controls of late-line chemotherapy. The majority of patients were treated on breast cancer-specific cohorts consistent with trends in Phase I trial design including more tumor specific cohorts.

scholarly journals Clinical Outcomes for Patients With Metastatic Breast Cancer Treated With Immunotherapy Agents in Phase I Clinical Trials

2021 ◽  
Vol 11 ◽  
Author(s):  
Anna R. Schreiber ◽  
Jodi A. Kagihara ◽  
Jennifer A. Weiss ◽  
Andrew Nicklawsky ◽  
Dexiang Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Clinical Outcomes ◽  
Single Agent ◽  
Metastatic Breast ◽  
Phase I Clinical Trials ◽  
University Of Colorado ◽  
The University

BackgroundImmuno-oncology (IO) agents have demonstrated efficacy across many tumor types and have led to change in standard of care. In breast cancer, atezolizumab and pembrolizumab were recently FDA-approved in combination with chemotherapy specifically for patients with PD-L1-positive metastatic triple-negative breast cancer (TNBC). However, the single agent PD-1/PD-L1 inhibitors demonstrate only modest single agent efficacy in breast cancer. The purpose of this study was to investigate the efficacy of novel IO agents in patients with metastatic breast cancer (MBC), beyond TNBC, treated in phase I clinical trials at the University of Colorado.MethodsWe performed a retrospective analysis using a database of patients with MBC who received treatment with IO agents in phase I/Ib clinical trials at the University of Colorado Hospital from January 1, 2012 to July 1, 2018. Patient demographics, treatments and clinical outcomes were obtained.ResultsWe identified 43 patients treated with an IO agent either as a single agent or in combination. The average age was 53 years; 55.8% had hormone receptor-positive/HER2-negative breast cancer, 39.5% TNBC and 4.7% HER2-positive. Patients received an average of 2 prior lines of chemotherapy (range 0-7) in the metastatic setting. Most patients (72.1%) received IO alone and 27.9% received IO plus chemotherapy. Median progression-free survival (PFS) was 2.3 months and median overall survival (OS) was 12.1 months. Patients remaining on study ≥ 6 months (20.9%) were more likely to be treated with chemotherapy plus IO compared to patients with a PFS &lt; 6 months (77.8% v. 14.7%). No differences in number of metastatic sites, prior lines of chemotherapy, breast cancer subtype, absolute lymphocyte count, or LDH were identified between patients with a PFS ≥ 6 months vs. &lt; 6 months.ConclusionsOur phase I experience demonstrates benefit from IO therapy that was not limited to patients with TNBC and confirms improved efficacy from IO agents in combination with chemotherapy. A subset of patients with MBC treated in phase I clinical trials with an IO agent derived prolonged clinical benefit. Predictors of response to immunotherapy in breast cancer remain uncharacterized and further research is needed to identify these factors.

Abstract A76: Efficacy of immunotherapy agents in patients with metastatic breast cancer treated in phase I clinical trials

2020 ◽  
Author(s):  
Jodi A. Kagihara ◽  
Jennifer A. Weiss ◽  
Andrew Nicklawsky ◽  
Dexiang Gao ◽  
Virginia F. Borges ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Metastatic Breast ◽  
Phase I Clinical Trials

scholarly journals Precision Medicine for Metastatic Breast Cancer

2015 ◽  
pp. e2-e7 ◽  
Author(s):  
Elise Deluche ◽  
Elisa Onesti ◽  
Fabrice Andre
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Dna Repair ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Precision Medicine ◽  
Metastatic Breast ◽  
Nucleotide Polymorphisms ◽  
Genomic Alterations ◽  
Pik3ca Mutations

Genomic studies have shown that large numbers of candidate targets are observed in breast cancer. Nevertheless, only a few of them are validated as relevant targets in clinical studies. Estrogen receptor (ER) and HER2 expressions could be associated with a level I evidence. Beyond ER and HER2, BRCA and PIK3CA mutations (when targeted with alpha-specific PI3K inhibitors) could be considered as promising targets in breast cancer since they have been associated with objective responses in phase I/II trials. In addition to these four molecular alterations, several others have shown promising results in preclinical studies and are being investigated in clinical trials. These genomic alterations include AKT1, ERBB2, and ESR1 mutations. These considerations highlight the lack of evidence for using multiplex technologies to individualize therapy in metastatic breast cancer. Sequencing multiple genes to treat metastatic breast cancer is very promising but should be done in the context of clinical trials, either to enrich phase I/II trials in patients with genomic alterations or to show medical usefulness of new biotechnologies like next-generation sequencing (NGS). Although most current approaches of precision medicine are aiming at targeting drivers, additional applications could be developed in the future. This includes the identification of DNA repair deficiencies, mechanisms of immune suppression, and identification of minority lethal subclones. Finally, one of the very promising applications of genomics for metastatic breast cancer is the identification of pathway activation or defects at the individual level. For example, gene expression and single nucleotide polymorphisms (SNP) signatures are being developed to detect kinase (such as mammalian target of rapamycin [mTOR]/CDK4) activations or DNA repair deficiencies.

scholarly journals Clinical outcomes of breast cancer patients treated in phase I clinical trials at University of Colorado Cancer Center

2020 ◽  
Vol 9 (23) ◽  
pp. 8801-8808
Author(s):  
Jennifer A. Weiss ◽  
Andrew Nicklawsky ◽  
Jodi A. Kagihara ◽  
Dexiang Gao ◽  
Christine Fisher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Phase I ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Cancer Center ◽  
Breast Cancer Patients ◽  
Phase I Clinical Trials ◽  
University Of Colorado

Contribution of clinical trials to improved clinical outcomes for patients with metastatic breast cancer (MBC).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e12596-e12596
Author(s):  
Ji Yun Lee ◽  
Sung Hee Lim ◽  
Min-Young Lee ◽  
Haesu Kim ◽  
Jin Seok Ahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Clinical Outcomes ◽  
Metastatic Breast

Clinical outcomes of patients with breast cancer in a phase I clinic: The M. D. Anderson Cancer Center experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1054-1054
Author(s):  
J. J. Wheler ◽  
A. Tsimberidou ◽  
S. Moulder ◽  
M. Cristofanill ◽  
D. Hong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Clinical Outcomes ◽  
Median Duration ◽  
Phase I Trial ◽  
Performance Status ◽  
Metastatic Breast ◽  
Ecog Performance Status

1054 Background: Patients with metastatic breast cancer refractory to standard therapy are eligible for phase I trials. We assessed prognostic factors and clinical outcomes for patients with breast cancer in a phase I clinic focused on targeted agents. Methods: We reviewed the medical records of sequential patients with metastatic breast cancer who presented to our phase I clinic from September 2004 to May 2008. We assessed the relationship between overall survival and patients’ demographic and clinical characteristics using both univariate and multivariate (Cox proportional hazard model) analyses. Results: Ninety-two patients were identified with median age of 53 years (range 28 to 83 years). The median number of prior therapies was 5 (range 1 to 16). The median follow-up of surviving patients is 7.4 months. The median overall survival is 6.7 (95% CI: 5.2, 9.7) months. In univariate analysis, factors predicting shorter survival were elevated Ca-125 (p = 0.001) (Ca27.29 was not significant), albumin < 3.5 g/dL (p = 0.002), worsening ECOG performance status (p = 0.004), absolute neutrophil count < 7.3 x 109/L (p = 0.004), ≥ 10 prior treatment regimens (p = 0.008), ≥ 5 prior chemotherapy-only regimens (p = 0.008), body mass index (BMI) < 25 (p = 0.018), and elevated platelet counts (p = 0.007). In multivariate analysis, independent factors predicting shorter survival were ≥10 prior treatments (vs. <10 prior treatments) (HR = 3.27; 95% CI 1.37, 7.81; p = 0.0077), ECOG performance status 2–3 (vs. 0–1) (HR = 2.92; 95% CI 1.28, 6.66; p = 0.01), and albumin < 3.5 g/dL (vs. > 3.5g/dL) (hazard ratio [HR] = 2.88; 95% CI; 1.41, 5.89; p = 0.004). Of 78 patients treated on a first phase I trial, 14 (18%) demonstrated stable disease (SD), with a median duration of 18 weeks (range 10–25). Of those 19 patients treated on a second phase I trial, 6 (32%) had SD with a median duration of 12 weeks (range 8–17). Two of 4 (50%) patients treated on a third phase I trial had SD with a median duration of 20 weeks (range 16–24). Conclusions: Patients with metastatic breast cancer referred for our phase I studies had a median survival of 6.6 months. In this preliminary analysis, independent factors predicting shorter survival were ≥ 10 prior treatments, worsening ECOG performance status and low albumin levels. No significant financial relationships to disclose.

scholarly journals Swiss Group for Clinical Cancer Research (SAKK) – Breast Cancer Project Group

2006 ◽  
Vol 9 (S1) ◽  
pp. 419-429
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Cancer Research ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Clinical Cancer Research ◽  
Cancer Project

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Swiss Group for Clinical Cancer Research (SAKK) – Breast Cancer Project Group. Clinical trials include: Randomized phase III trial of Herceptin followed by chemotherapy plus Herceptin versus the combination of Herceptin and chemotherapy as palliative treatment in patients with HER2-overexpressing advanced/metastatic breast cancer. Protocol SAKK 22/99Trastuzumab monotherapy followed by the combination of trastuzumab and letrozole in post-menopausal women with ER-positive, HER-2 positive advanced breast cancer resistant to a nonsteroidal aromatase inhibitor. A multicenter two-step phase II trial Protocol SAKK 23/03Phase I–II trial of capecitabine and vinorelbine in elderly patients ( 65 years) with metastatic breast cancer with and without bone involvement. Protocol SAKK 25/99Phase I/II trial of capecitabine with weekly paclitaxel for advanced breast cancer. Protocol SAKK 26/00

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