scholarly journals Efficacy and predictive factors of immune checkpoint inhibitors in metastatic breast cancer: a systematic review and meta-analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592094092 ◽  
Author(s):  
Yutian Zou ◽  
Xuxiazi Zou ◽  
Shaoquan Zheng ◽  
Hailin Tang ◽  
Lijuan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Metastatic Breast ◽  
Cd8 T Cell ◽  
First Line ◽  
Grade 3

Background: Immune checkpoint inhibitors (ICIs) have shown encouraging treatment efficacy for metastatic breast cancer in several clinical trials. However, response only occurred in a small population. Evidence predicting response and survival of patients with metastatic breast cancer following ICI treatment with existing biomarkers has not been well summarized. This review aimed to summarize the efficacy and predictive factors of immune checkpoint therapy in metastatic breast cancer, which is critical for clinical practice. Methods: PubMed, Embase, Cochrane Library, Web of Science, www.clinicaltrials.gov , and meeting abstracts were comprehensively searched to identify clinical trials. The outcomes were objective response rate (ORR), treatment-related adverse events (trAEs), immune-related adverse events (irAEs), progression-free survival (PFS), and overall survival (OS). Results: In this review, 27 studies with 1746 patients were included for quantitative synthesis. The pooled ORR was 19% [95% confidence interval (CI) = 12–27%]. Programmed death-ligand 1 (PD-L1)-positive patients had a higher response rate [odds ratio (OR) = 1.44, p = 0.01]. First-line immunotherapy had a better ORR than second-line immunotherapy (OR = 2.00, p = 0.02). Tumor-infiltrating lymphocytes (TILs) ⩾5% (OR = 2.53, p = 0.002) and high infiltrated CD8+ T-cell level (OR = 4.33, p = 0.006) were ideal predictors of immune checkpoint therapy response. Liver metastasis indicated poor response (OR = 0.19, p = 0.009). However, the difference was non-significant in ORR based on age, performance status score, lymph node metastasis, and lactate dehydrogenase (LDH) level. In addition, the PD-L1-positive subgroup had a better 1-year PFS (OR = 1.55, p = 0.04) and 2-year OS (OR = 2.28, p = 0.02) following ICI treatment. The pooled incidence during ICI therapy of grade 3–4 trAEs was 25% (95% CI = 16–34%), whereas for grade 3–4 irAEs it was 15% (95% CI = 11–19%). Conclusions: Metastatic breast cancer had modest response to ICI therapy. PD-L1-positive, first-line immunotherapy, non-liver metastasis, and high TIL and CD8+ T-cell infiltrating levels could predict better response to ICI treatment. Patients with PD-L1-positive tumor could gain more survival benefits from immune checkpoint therapy.

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

Circulating PD-L1 (programmed death-ligand 1) and outcomes in a HER2-positive metastatic breast cancer cohort treated with first-line trastuzumab.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1024-1024 ◽  
Author(s):  
Ayesha Ali ◽  
Laura Krecko ◽  
Kim Leitzel ◽  
Suhail M. Ali ◽  
Joseph J. Drabick ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
First Line ◽  
Her2 Positive ◽  
Breast Cancer Cohort

1024 Background: Recently the immune checkpoint inhibitors (ICIs) have demonstrated efficacy across a wide variety of cancers, but have been less effective in breast cancer. PD-L1 (B7-H1, CD274) is a ligand produced by many tumor cells and some immune cells, and suppresses the T cell immune response. This allows tumor cells to escape immune detection. PD-L1 is used as a companion tumor tissue IHC biomarker for patient selection for some of the FDA-approved ICIs (pembrolizumab), but not for others (nivolumab, atezolizumab). Circulating PD-L1 has been detected in multiple myeloma, renal, lung, and gastric cancer, but not in breast cancer. Here we correlated serum PD-L1 levels with outcome in a HER2-positive metastatic breast cancer cohort treated with trastuzumab. Methods: Pretreatment serum was obtained from 63 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. A novel ELLA microfluidic channel immunoassay platform (ProteinSimple, San Jose, CA) was employed to quantitate serum PD-L1. Serum PD-L1 levels were analyzed using continuous, quartile, and dichotomous (25%, median, and 75%) cutpoints. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Results: On a continuous basis, patients with higher serum PD-L1 had a significantly reduced PFS (p = 0.045) and overall survival OS (p = 0.004) compared to patients with lower serum PD-L1 levels. Patients with the higher quartiles of serum PD-L1 also trended to have reduced PFS (0.11) and significantly reduced OS (p = 0.015) compared to the lower quartiles of serum PD-L1. Finally, using either the 25th or 75th percentile of serum PD-L1 as dichotomous cutpoint, patients with higher serum PD-L1 had significantly reduced OS (p = 0.04). Conclusions: Higher circulating PD-L1 levels were prognostic for reduced PFS and OS in HER2-positive metastatic breast cancer patients treated with first-line trastuzumab. Circulating PD-L1 deserves further study for prognostic and predictive biomarker utility in larger trials of immune checkpoint inhibitors and other immunotherapies in breast and other cancers. AA, LK contributed equally.

scholarly journals Predictive Biomarkers for Immune Checkpoint Inhibitors in Metastatic Breast Cancer

2020 ◽  
Author(s):  
Abirami Sivapiragasam ◽  
Prashanth Ashok Kumar ◽  
Ethan S. Sokol ◽  
Lee A. Albacker ◽  
Jonathan K. Killian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Metastatic Breast ◽  
Predictive Biomarkers

Phase III Trial of Epirubicin Plus Paclitaxel Compared With Epirubicin Plus Cyclophosphamide As First-Line Chemotherapy for Metastatic Breast Cancer: United Kingdom National Cancer Research Institute Trial AB01

2005 ◽  
Vol 23 (33) ◽  
pp. 8322-8330 ◽  
Author(s):  
Ruth E. Langley ◽  
James Carmichael ◽  
Alison L. Jones ◽  
David A. Cameron ◽  
Wendi Qian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Survival Time ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
Line Chemotherapy

Purpose To compare the effectiveness and tolerability of epirubicin and paclitaxel (EP) with epirubicin and cyclophosphamide (EC) as first-line chemotherapy for metastatic breast cancer (MBC). Patients and Methods Patients previously untreated with chemotherapy (except for adjuvant therapy) were randomly assigned to receive either EP (epirubicin 75 mg/m2 and paclitaxel 200 mg/m2) or EC (epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for a maximum of six cycles. The primary outcome was progression-free survival; secondary outcome measures were overall survival, response rates, and toxicity. Results Between 1996 and 1999, 705 patients (353 EP patients and 352 EC patients) underwent random assignment. Patient characteristics were well matched between the two groups, and 71% of patients received six cycles of treatment. Objective response rates were 65% for the EP group and 55% for the EC group (P = .015). At the time of analysis, 641 patients (91%) had died. Median progression-free survival time was 7.0 months for the EP group and 7.1 months for the EC group (hazard ratio = 1.07; 95% CI, 0.92 to 1.24; P = .41), and median overall survival time was 13 months for the EP group and 14 months for the EC group (hazard ratio = 1.02; 95% CI, 0.87 to 1.19; P = .8). EP patients, compared with EC patients, had more grade 3 and 4 mucositis (6% v 2%, respectively; P = .0006) and grade 3 and 4 neurotoxicity (5% v 1%, respectively; P < .0001). Conclusion In terms of progression-free survival and overall survival, there was no evidence of a difference between EP and EC. The data demonstrate no additional advantage to using EP instead of EC as first-line chemotherapy for MBC in taxane-naïve patients.

Ifosfamide and mitoxantrone as first-line chemotherapy for metastatic breast cancer.

1993 ◽  
Vol 11 (3) ◽  
pp. 461-466 ◽  
Author(s):  
J E Perez ◽  
M Machiavelli ◽  
B A Leone ◽  
A Romero ◽  
M G Rabinovich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Complete Response ◽  
Severe Toxicity ◽  
First Line ◽  
Metastatic Breast Carcinoma ◽  
Time To Treatment Failure ◽  
Grade 3 ◽  
Line Chemotherapy

PURPOSE A phase II trial was performed to evaluate the efficacy and toxicity of a combination of ifosfamide (IFX) and mitoxantrone (MXN) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS Between January 1990 and August 1991, 48 patients with metastatic breast cancer were entered onto the study. Therapy consisted of IFX 2 g/m2 given as a 1-hour intravenous (IV) infusion on days 1 to 3; mesna 400 mg/m2 as an IV bolus immediately before and 4 hours after IFX administration and 2,000 mg orally 8 hours after IFX administration on days 1 to 3; and MXN 12 mg/m2 as an i.v. bolus on day 3. Cycles were repeated every 21 days until progressive disease (PD) or severe toxicity developed. RESULTS One patient was considered not assessable for response. Objective regression (OR) was observed in 28 of 47 patients (60%; 95% confidence interval, 46% to 74%). Six patients (13%) had a complete response (CR) and 22 (47%) had a partial response (PR). The median time to treatment failure for the whole group was 9 months (range, 1 to 28); median survival was 19 months (range, 2 to 28). There were no treatment-related deaths. The limiting toxicity was myelosuppression. Leukopenia occurred in 37 patients (77%) and was grade 3 or 4 in 19 patients (40%). Nausea and vomiting were observed in 38 patients (80%), mucositis in 16 patients (33%), and grade 2 hematuria in two patients (4%). Eight patients (16%) developed mild neurotoxicity. CONCLUSION The combination of IFX plus MXN is an active regimen against metastatic breast cancer with moderate toxicity that deserves further evaluation.

Weekly First-Line Chemotherapy of Metastatic Breast Cancer with Cyclophosphamide and Epirubicin

1992 ◽  
Vol 78 (5) ◽  
pp. 338-340
Author(s):  
Emilio Alba ◽  
Esperanza Blanco ◽  
Enrique Aranda ◽  
Roberto Lasso ◽  
Lorenzo Alonso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Advanced Disease ◽  
Metastatic Breast ◽  
Confidence Limits ◽  
First Line ◽  
Weekly Chemotherapy

Forty-six patients with metastatic breast cancer who had not received previous chemotherapy for advanced disease entered a phase II trial of weekly chemotherapy with cyclophosphamide (250 mg/m2) + epirubicin (25 mg/m2) for 16 weeks. The overall response rate was 61 % (95 % confidence limits, 47-75 %), with 10 complete and 17 partial responses. Toxicity was mild and confined to nausea and vomiting and asymptomatic neutropenia (except in 2 cases). Sixty-three per cent of patients had no side effects. Weekly cyclophosphamide + epirubicin is an active and nontoxic regimen for patients with metastatic breast cancer who have had no prior anthracycline-containing adjuvant chemotherapy.

Doxorubicin and Paclitaxel Versus Fluorouracil, Doxorubicin, and Cyclophosphamide as First-Line Therapy for Women With Metastatic Breast Cancer: Final Results of a Randomized Phase III Multicenter Trial

2001 ◽  
Vol 19 (6) ◽  
pp. 1707-1715 ◽  
Author(s):  
Jacek Jassem ◽  
Tadeusz Pieńkowski ◽  
Anna Płuzańska ◽  
Svetislav Jelic ◽  
Vera Gorbunova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Time To Progression ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

PURPOSE: This phase III trial compared the efficacy and safety of doxorubicin and paclitaxel (AT) to 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line therapy for women with metastatic breast cancer. PATIENTS AND METHODS: A total of 267 women with metastatic breast cancer were randomized to receive either AT (doxorubicin 50 mg/m2 followed 24 hours later by paclitaxel 220 mg/m2) or FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2), each administered every 3 weeks for up to eight cycles. Patients had to have measurable disease and an Eastern Cooperative Oncology Group performance status of 0 to 2. Only one prior non–anthracycline, nontaxane-containing adjuvant chemotherapy regimen was allowed. RESULTS: Overall response rates for patients randomized to AT and FAC were 68% and 55%, respectively (P = .032). Median time to progression and overall survival were significantly longer for AT compared with FAC (time to progression 8.3 months v 6.2 months [P = .034]; overall survival 23.3 months v 18.3 months [P = .013]). Therapy was generally well-tolerated (median of eight cycles delivered in each arm). Grade 3 or 4 neutropenia was more common with AT than with FAC (89% v 65%; P < .001); however, the incidence of fever and infection was low. Grade 3 or 4 arthralgia and myalgia, peripheral neuropathy, and diarrhea were more common with AT, whereas nausea and vomiting were more common with FAC. The incidence of cardiotoxicity was low in both arms. CONCLUSION: AT conferred a significant advantage in response rate, time to progression, and overall survival compared with FAC. Treatment was well-tolerated with no unexpected toxicities.

Gemcitabine and docetaxel combination regimen in metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1107-1107
Author(s):  
D. Karacetin ◽  
O. Maral ◽  
O. Aksakal ◽  
B. Okten ◽  
B. Yalçın ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Response Rate ◽  
Menopausal Status ◽  
Metastatic Breast ◽  
Complete Response ◽  
Combination Regimen ◽  
Breast Cancer Patients ◽  
Grade 3

1107 Background: No standart chemotherapy regimen has been estabilished for the treatment of patients with metastatic breast cancer. The gemcitabine and docetaxel combination has been shown to be synergistic . This study is conducted to verify the clinical efficacy and safety of gemcitabine and docetaxel combination therapy in metastatic breast cancer. Methods: 27 metastatic breast cancer patients were treated with gemcitabine-docetaxel combination . Gemcitabine 1,250 mg/m2 IV infusion, on day 1 and 8, and docetaxel 70 mg/m2 on day 1 in 21 day cycles. 4–6 cycles of chemotherapy were repeated every 3 weeks. The primary endpoint was response rate, and survival. Results: The median age was 50 years (range,32–77). Performans status (ECOG) was 0–1. Hormone receptor status: ER+/ER-; 11/16, PR+/PR-; 14/13. Menopausal status were: 11 premenopausal, 16 postmenopausal. Of the 27 evaluable patients, there were 11 (40.7%) partial responses and no complete response. Overall response rate was 40.7%. Median time to progression was 7 months, and median survival was 14 months. Toxicities included grade 3–4 neutropenia in 9 (30%), thrombocytopenia in 6 (22%), anemia in 3(9%). There were no treatment releated deaths Conclusions: The combination of gemcitabine and docetaxel has shown favorable toxicity profile and promising activity in metastatic breast cancer patients. No significant financial relationships to disclose.

Phase II trial of pegylated liposomal doxorubicin-cyclophosphamide combination as first-line chemotherapy in elderly metastatic breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19565-19565 ◽  
Author(s):  
P. R. Dufour ◽  
F. Rousseau ◽  
N. Meyer ◽  
T. Delozier ◽  
D. Serin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Liposomal Doxorubicin ◽  
Phase Ii Trial ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
First Line ◽  
Grade 3 ◽  
Line Chemotherapy

19565 Background: Although the majority of metastatic breast cancer (MBC) patients (pts) responds to endocrine therapy, treatment failure is a concern, as well as front-line therapy for pts with ER/PR negative disease.The combination of anthracyclines (A) and cyclophosphamide (C) is active in younger pts, but cardiac toxicity of A in elderly MBC pts has to be considered. Pegylated liposomal doxorubicin (PLD) (Caelyx®) is active in MBC and has much less cardiotoxicity than A, and we present the preliminary data of the PLD/C in elderly MBC pts. Methods: This was a multicentric phase II trial. Inclusion criteria included: pts aged between 65 and 75, histologically proven measurable MBC, ECOG PS 0–1, LVEF = 50%, first-line chemotherapy for MBC. Prior adjuvant chemotherapy was allowed if stopped for = 6 or 12 months without and with anthracyclines, respectively. Endocrine therapy either in the adjuvant or metastatic setting had to be stopped for = 1 month. All pts gave a written informed consent. The treatment schedule was : PLD 40mg/m2 and C 500mg/m2 d1 every 4 weeks. Efficacy as well as response duration and tolerance were the primary and secondary end-points, respectively. Results: 35 patients were enrolled (Median age 71.3, range 65.6–75.9). A total of 166 cycles have been administered. The median number of cycles was 6 (range 1–9). No toxic death was reported, one patient died of diabetes mellitus decompensation. No congestive heart failure or decrease in LVEF was reported, although 1 pt experience grade 3 dyspnea and stopped treatment. Other (gr3–4) NCI-CTC toxicity included: neutropenia in 7 (gr3) and 3 (gr4) pts; gr3 mucositis (4). No febrile neutropenia was reported. Grade 3 hand-foot syndrome occurred in 1 pt, whereas treatment was stopped due to a generalized rash in 1 pt. An objective response (CR + PR) was achieved in 10 (28,6%) pts (1 CR and 8 PR), and a disease control in 24 (68.6%) with a progression free survival of 8.8 months and a median survival of 20.4 months Conclusions: The LPD-C combination is active in elderly MBC pts, with an acceptable toxicity profile. No significant financial relationships to disclose.

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