Nanoparticle albumin-bound (Nab) paclitaxel (P) in combination with bevacizumab (B) with and without gemcitabine (G): Early experience at the Braman Family Breast Cancer Institute

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10748-10748
Author(s):  
C. F. Lobo ◽  
G. Lopes ◽  
O. Silva ◽  
S. Gluck
Keyword(s):  
Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
Preliminary Evidence ◽  
Clinical Activity ◽  
Hemorrhagic Complication ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive ◽  
Heavily Pretreated ◽  
Grade 3

10748 Background: Nab-P improves outcomes when compared against single agent cremophor-based P, as does the addition of bevacizumab or gemcitabine to the same agent. There are no available data regarding combinations of Nab-P with B and/or G. Ongoing investigational efforts are evaluating various doublets with these agents, but, to the best of our knowledge, not all 3 of them in the same regimen. All drugs are currently FDA-approved in the treatment of breast cancer. Methods: Review of single-institution experience, evaluating safety and preliminary evidence of activity with the use of Nab-P and B with and without G in heavily pretreated her2neu negative metastatic breast cancer patients. Assessment of response was undertaken by the investigators independently of treating physician. RECIST criteria were used. Three patients received Nab-P and B at the following doses: Nab-P 100 mg/m2, B 10 mg/kg every 2 weeks, and 2 patients received all 3 drugs as follows: Nab-P 100 mg/m2, G 1,000 mg/m2, B 10 mg/kg every 2 weeks. Results: Five women have been evaluated. Median age was 51 (range 34–69). Two patients had hormone-receptor positive disease and 3 had ER/PR/Her2neu-negative cancer. Prior number of regimens was 3 (range 2–7). Four patients had been treated with a taxane. One received both paclitaxel and docetaxel, and 3 docetaxel only. A median of 5 cycles have been administered (range 3–9). First-cycle grade 3/4 toxicity was seen in only one patient who had a baseline grade 2 thrombocytopenia that progressed to grade 3. The thrombocytopenia resolved without requiring transfusion and without any hemorrhagic complication. Another patient developed grade 2 peripheral neuropathy. Two patients are not yet assessable for response. At time of first evaluation 1 patient had progressive disease (Nab-P, B; 7 prior lines of treatment), one had stable disease (Nab-P, B, G; 3 prior lines of therapy, including docetaxel), and 1 had a partial response (Nab-P, B, G; 2 prior therapies, including docetaxel). Conclusions: These very preliminary data suggest that Nab-P in combination with B with and without G is a safe regimen and formal Phase I/II trials are being developed to confirm its clinical activity. [Table: see text]

Lapatinib with trastuzumab for heavily treated HER2-positive metastatic breast cancer (mBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11561-e11561
Author(s):  
Miguel J. Sotelo ◽  
Luis Manso ◽  
José Ángel Garcia Saenz ◽  
Eva M. Ciruelos ◽  
Fernando Moreno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Heavily Pretreated ◽  
Previously Treated ◽  
Grade 3

e11561 Background: Trastuzumab and lapatinib show complementary and non-cross resistant mechanisms of anti-HER2 action. Dual HER2 blockade has been preclinically and clinically assessed with encouraging results. Trastuzumab and lapatinib combination is effective in terms of survival in patients with heavily pretreated HER2-positive mBC. We aim to report our experience with lapatinib plus trastuzumab in this setting. Methods: Descriptive retrospective study of trastuzumab plus lapatinib activity in patients with HER2-overexpressing metastatic breast cancer treated in two institutions from 01/2007 to 12/2012. The objective of this analysis is to report the response rate (RR), progression-free survival (PFS) and toxicity. Results: 23 HER2-positive mBC patients previously treated with trastuzumab received trastuzumab plus lapatinib based therapy. 15 patients (65%) received 2 or more previous lines. 17 patients (74%) had visceral disease. Chemotherapy (CT) was added to the dual HER2 blockade treatment in 13 patients (56%) whereas hormonotherapy (HT) was added in 8 patients (35%) and 2 patients (9%) received lapatinib plus trastuzumab without any other agent. Chemotherapeutic drugs most used were: capecitabine (54%) and vinorelbine (15%). RR: partial response 22% (5/23), stable disease 39% (9/23). Median of follow-up was 11 months. PFS in the overall population was 4 months. PFS in patients with CT was 5 months, while PFS in patients with HT was only 2. PFS in hormone receptor positive and negative was 3 and 5 months respectively. The most common toxicities were: diarrhea (48%), anemia (39%), asthenia (39%) and hand-and-foot syndrome (17%). Grade ≥ 3 toxicity was diarrhea (26%) and hand-and-foot syndrome (9%). The incidence of cardiotoxicity was 9% (grade 2). Conclusions: These findings suggest that dual HER2 blockade in combination with CT is feasible and active in heavily pretreated HER2-positive mBC patients. However, further investigation is warranted to demonstrate superiority over sequential blockade with trastuzumab and lapatinib in this setting.

Phase 1b study of H3B-6545 in combination with palbociclib in women with metastatic estrogen receptor–positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13025-e13025
Author(s):  
Stephen R. D. Johnston ◽  
Timothy J. Pluard ◽  
Judy S. Wang ◽  
Erika P. Hamilton ◽  
Dejan Juric ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sinus Bradycardia ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Metastatic Setting ◽  
Estrogen Receptor Positive ◽  
Heavily Pretreated ◽  
Phase 1B ◽  
Grade 3

e13025 Background: H3B-6545, a highly Selective ERα Covalent Antagonist (SERCA), inactivates both wild-type and mutant ERα by targeting cysteine 530 and enforcing a unique antagonist conformation. At the dose of 450 mg daily, H3B-6545 has a manageable safety profile and demonstrated preliminary single-agent antitumor activity in heavily pretreated ER+, HER2- mBC patients (Hamilton et al, San Antonio Breast Cancer Symposium, 2020). Methods: The study evaluates the safety, pharmacokinetics (PK), and efficacy of H3B-6545 in combination with palbociclib in patients with ER+, HER2- metastatic breast cancer (MBC). The escalation phase enrolls patients with 2 or more prior therapies in the metastatic setting. Up to one prior chemotherapy and up to one prior CDK4/6 inhibitor were allowed. Results: As of January 31, 2021, 10 patients were enrolled; 7 in Cohort 1 (H3B-6545 300 mg QD and palbociclib 100 mg QD) and 3 in Cohort 2 (H3B-6545 300 mg QD and palbociclib 125 mg QD). One patient in Cohort 1 was not evaluable for dose limiting toxicity (DLT) assessment and no DLT was observed in the 6 evaluable patients. One patient discontinued study treatment because of progression and no patients discontinued study treatment due to adverse events (AE). Grade 3 or 4 neutropenia and thrombocytopenia were observed in 4 patients and 1 patient, respectively. One patient had grade 3 hypercalcemia, generalized muscle weakness, hypophosphatemia, fall, and anemia and one patient had grade 3 lipase increase. Four patients had grade 1 bradycardia or sinus bradycardia (asymptomatic) 1 patient had grade 2 sinus bradycardia (symptomatic, no intervention required). Preliminary PK analysis suggested no clinically relevant drug-drug interactions between H3B-6545 and palbociclib, to be confirmed with data from additional cohorts. Recruitment is currently ongoing in Cohort 2. Updated results will be presented. Conclusions: H3B-6545, in combination with palbociclib, was well-tolerated. Clinical trial information: NCT04288089.

Bortezomib and capecitabine in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines: Final results of a phase I/II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1072-1072 ◽  
Author(s):  
P. Schmid ◽  
A. Regierer ◽  
P. Kiewe ◽  
W. Schippinger ◽  
R. Greil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Antitumour Activity ◽  
Metastatic Breast ◽  
26S Proteasome ◽  
Breast Cancer Patients ◽  
Hand Foot Syndrome ◽  
Heavily Pretreated ◽  
Grade 3

1072 Background: Capecitabine has shown substantial activity in taxane and/or anthracycline pretreated breast cancer patients. Bortezomib, a 26S proteasome inhibitor, has been shown to increase sensitivity to chemotherapy. This phase I/II trial was initiated to evaluate the combination of capecitabine and bortezomib in heavily pretreated patients with metastatic breast cancer. Methods: Patients with metastatic breast cancer and prior taxane and/or anthracycline therapy were treated with bortezomib (1.0–1.3 mg/m2; days 1, 4, 8 & 11) and capecitabine (1,500–2,500 mg/m2, days 1–14) in 3-weeks intervals for up to 8 cycles. Primary endpoints were to determine the optimal doses for the combination (phase I) and the tumor response rate (RR) (phase II). Secondary endpoints included safety, time to progression (TTP), duration of response (DR), and overall survival (OS). Results: A total of 35 patients were enrolled and 29 patients were assessable for response. The majority of patients had received 2 or 3 lines of chemotherapy (69% and 14%, respectively) prior to the study. The maximum tolerated doses (MTD) were bortezomib 1.3 mg/m2 and capecitabine 2500 mg/m2. Dose limiting toxicities were Grade 3 stomatitis in 1 out of 6 patients at 1.0/2,000 and Grade 3 diarrhea in 1 out of 6 patients at 1.3/2,500. Myelosuppression was low. Non-hematological toxicities were generally mild to moderate with no G4 toxicity being observed. Most common side effects were thrombocytopenia (Grade 3/4 27% of patients), diarrhea (18%), hand-foot syndrome (12%), peripheral neuropathy (12%), leucopenia (9%) and asthenia (9%). The overall RR was 17.2% and an additional 31% of patients had stable disease (31%; 4 unconfirmed). In the 21 patients treated at the MTD, RR was 17.6% and 47% of patients had SD. Median TTP and OS were 3.5 months (95% CI 1.9–4.4) and 7.5 months (95% CI 5.6–14.6), respectively. Median DR was 4.4 months. Conclusions: The combination of bortezomib and capecitabine is well tolerated and has moderate antitumour activity in heavily pretreated breast cancer. [Table: see text]

Phase I Clinical Trial of Alitretinoin and Tamoxifen in Breast Cancer Patients: Toxicity, Pharmacokinetic, and Biomarker Evaluations

2001 ◽  
Vol 19 (10) ◽  
pp. 2754-2763 ◽  
Author(s):  
Julia A. Lawrence ◽  
Peter C. Adamson ◽  
Rafael Caruso ◽  
Catherine Chow ◽  
David Kleiner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Plasma Concentrations ◽  
Density Lipoprotein ◽  
Metastatic Breast ◽  
Tamoxifen Therapy ◽  
Breast Cancer Patients ◽  
Grade 3 ◽  
Mib 1

PURPOSE: To determine the overall and dose-limiting toxicities (DLTs) of alitretinoin (9-cis-retinoic acid) in combination with tamoxifen and the pharmacokinetics of alitretinoin alone and when combined with tamoxifen in patients with metastatic breast cancer. The effect of tamoxifen and alitretinoin on MIB-1, a marker of proliferation, in unaffected breast tissue was explored. PATIENTS AND METHODS: Eligible patients had metastatic breast cancer. Previous tamoxifen therapy was allowed. Planned dose levels for alitretinoin ranged from 50 to 140 mg/m2/d with 20 mg/d tamoxifen in all patients after 4 weeks of alitretinoin as a single agent. Plasma concentrations of alitretinoin and retinol were measured at baseline and after 1, 2, and 3 months. Breast core biopsies were obtained at baseline and after 2 months of therapy. RESULTS: Twelve patients with metastatic breast cancer received a total of 86 cycles of therapy. At 90 mg/m2/d, three of five patients experienced a DLT: grade 3 headache, grade 3 hypercalcemia, and grade 3 noncardiogenic pulmonary edema. At 70 mg/m2/d, one of six patients experienced a DLT (headache), and this level was considered the maximal tolerated dose in this study. Three toxicities occurred that had not been reported previously with alitretinoin: an asymptomatic delay in dark adaptation, a marked decrease in high-density lipoprotein cholesterol, and the occurrence of enthesopathy. Two of the nine assessable patients had a durable clinical response: one partial response and stable disease for 18 months and one complete response in continuous remission for 48+ months. Both responding patients were estrogen receptor–positive and had had previous tamoxifen therapy. There was a high degree of interpatient variability of plasma alitretinoin concentrations, although a significant decline in alitretinoin plasma levels over time was observed. MIB-1 scores declined in four of the eight paired breast specimens obtained. CONCLUSION: The combination of tamoxifen and alitretinoin is well tolerated and has antitumor activity in metastatic breast cancer. The recommended phase II dose is 70 mg/m2/d with 20 mg/d tamoxifen.

scholarly journals Trastuzumab and Gemcitabine in Pretreated HER2 Overexpressing Metastatic Breast Cancer Patients: Retrospective Analysis of Our Series

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Vincenzo Di Lauro ◽  
Elena Torrisi ◽  
Ettore Bidoli ◽  
Daniela Quitadamo ◽  
Sara Cecco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Response Rate ◽  
Target Therapy ◽  
Metastatic Breast ◽  
Clinical Activity ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Heavily Pretreated

Trastuzumab-based regimes improved clinical outcome in women with overexpressing HER2 metastatic breast cancer, mainly due to the availability of different combination therapies, clinically active and well tolerated. In this study we retrospectively evaluated clinical activity and toxicity of trastuzuamb plus gemcitabine regimen in heavily pretreated HER2 positive metastatic breast cancer patients. Although the observed population was heavily pretreated, the evaluated regimen was notably effective in terms of response rate, time to progression and survival, with very mild toxicity. These data suggest that in over expressing HER2 metastatic breast cancer patients, sequential trastuzumab based chemotherapeutic regimens can achieve good response rate with prolonged TTP in responding patients, even after other target therapy such as lapatinib based combinations.

Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer

2005 ◽  
Vol 23 (23) ◽  
pp. 5314-5322 ◽  
Author(s):  
Stephen Chan ◽  
Max E. Scheulen ◽  
Stephen Johnston ◽  
Klaus Mross ◽  
Fatima Cardoso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Dose Level ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Time To Tumor Progression

Purpose In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated. Patients and Methods Patients (n = 109) were randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, adverse events, and pharmacokinetics of temsirolimus. Results Temsirolimus produced an objective response rate of 9.2% (10 partial responses) in the intent-to-treat population. Median time to tumor progression was 12.0 weeks. Efficacy was similar for both dose levels but toxicity was more common with the higher dose level, especially grade 3 or 4 depression (10% of patients at the 250-mg dose level, 0% at the 75-mg dose level). The most common temsirolimus-related adverse events of all grades were mucositis (70%), maculopapular rash (51%), and nausea (43%). The most common, clinically important grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%). Conclusion In heavily pretreated patients with locally advanced or metastatic breast cancer, 75 and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a generally tolerable safety profile.

scholarly journals Effect and Safety of Anti-PD-1/PD-L1 Monotherapy for Metastatic Breast Cancer: A meta-analysis

2019 ◽  
Author(s):  
Yihang Qi ◽  
Xiangyi Kong ◽  
Xiangyu Wang ◽  
Jie Zhai ◽  
Yi Fang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Rate ◽  
Response Rate ◽  
Meta Analysis ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Clinical Activity ◽  
Breast Cancer Patients ◽  
Severe Grade

Abstract Background. Given that no approved targeted agents for metastatic triple-negative breast cancer (mTNBC) and no opportunity of surgery for metastatic breast cancer (MBC), new treatment options are urgently to be discovered. The anti-PD-1/PD-L1 immunotherapy may be effective, and what we should be aware of is the response rate and adverse events. Methods. The PUBMED, EMBASE, Cochrane and www.clinicaltrials.gov databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1; metastatic; breast cancer. R© package Meta was used to pool incidence. Results. Six studies including 586 advanced breast cancer patients treated with anti-PD-1/PD-L1 agents were included in this meta-analysis. The anti-PD-1/PD-L1 agents include pembrolizumab, atezolizumab and avelumab. Among these patients, CR was 1.26%, PR was 7.65%, ORR was 9.85% and DCR was 18.33%. We also found that the response rate was closely associated with the expression of PD-L1 biomarker (PD-L1+ vs PD-L1-): the CR was 2.71% vs 0.00%; the PR was 9.93% vs 2.69%; the ORR was 10.62% vs 3.07%; the DCR was 17.95% vs 4.71%. 1-year overall survival rate and 6-months progression-free survival rate were 43.34% and 17.24%. Respectively, the overall incidence of AEs was 64.18% in any grade and 12.94% in severe grade. The incidence of irAEs was 14.75%. Besides, the incidence of discontinue and death due to treatment-related AEs was about 3.06% and 0.31% respectively. When the detailed AEs were analyzed, most treatment-related AEs of any grade were arthraigia, asthenia, decreased appetite; most common treatment-related AEs of severe grade were anemia, autoimmune hepatitis, diarrhea; the most common irAEs were hypothyroidism , followed by hyperthyroidism, pneumonitis and infusion-related reaction. Conclusions. Anti-PD-1/PD-L1 monotherapy showed a manageable safety profile and had a durable anti-tumor clinical activity in a subset of patients with mTNBC or MBC. PD-L1 expression may be correlated to a higher probability of clinical response.

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