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Phase II study of Pseudomonas aeruginosa-Mannose-Sensitive hemagglutinin in combination with capecitabine for Her-2-negative metastatic breast cancer pretreated with anthracycline and taxane.

Lv F, Cao J, Liu Z, Wang Z, Zhang J, Zhang S, Wang L, Zhao X, Shao Z, Wang B, Hu X - PLoS ONE (2015)

Bottom Line: PA-MSHA has a good safety profile, with only 6 patients (6.2 %) discontinuing treatment.PA-MSHA did not increase capecitabine-related toxicities such as hand-foot syndrome, nausea, and vomiting.Adding PA-MSHA to capecitabine has a good safety profile in patients with heavily pre-treated MBC, although benefit from this regimen might occur only in patients with moderate PA-MSHA-related adverse events.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

ABSTRACT

Purpose: Metastatic breast cancer (MBC) remains an incurable disease despite major therapeutic advances. Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) has been established to have anti-proliferative effects against breast cancer cells in preclinical experiments, and is indicated for treatment of cancer in China. We performed a phase II trial combining PA-MSHA with capecitabine in patients with heavily pretreated MBC.

Methods: Eligibility criteria included human epidermal growth factor receptor 2-negative MBC, prior therapy with anthracyclines and taxanes, at least one prior chemotherapy regimen for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. PA-MSHA 1 mg was administered subcutaneously every other day and capecitabine 1000 mg/m2 orally twice a day for 2 weeks on, 1 week off. The primary end point was progression-free survival.

Results: A total of 97 patients were enrolled. Median progression-free survival (PFS) was 4.0 months [95 % confidence interval (CI) 3.0-4.9], which was not significantly different from that in historical controls. However, median PFS was significantly longer (8.2 months; 95 % CI 6.7-9.7) in 24 patients with moderate immune-related adverse events (irAEs) such as fever or skin induration at the injection site than in those with no or mild irAEs (3.1 months, 95 % CI 2.5-3.6; p = 0.003). Overall survival was also improved in these patients (25.4 vs. 16.4 months; p = 0.044). PA-MSHA has a good safety profile, with only 6 patients (6.2 %) discontinuing treatment. PA-MSHA did not increase capecitabine-related toxicities such as hand-foot syndrome, nausea, and vomiting.

Conclusion: Adding PA-MSHA to capecitabine has a good safety profile in patients with heavily pre-treated MBC, although benefit from this regimen might occur only in patients with moderate PA-MSHA-related adverse events.

Trial registration: ClinicalTrials.gov NCT01380808.

No MeSH data available.


Related in: MedlinePlus

PFS curve of patients with different grades of irAEs.Patients with grade 2 or higher irAEs (N = 24, events 20) had longer PFS than those who had no or grade 1 irAEs (N = 69, events 63) (p = 0.003).
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pone.0118607.g002: PFS curve of patients with different grades of irAEs.Patients with grade 2 or higher irAEs (N = 24, events 20) had longer PFS than those who had no or grade 1 irAEs (N = 69, events 63) (p = 0.003).

Mentions: After a median follow-up of 22 months, 83 (85.6%) patients had disease progression and 38 (39.2%) patients had died. Twenty-one patients achieved PR and no patient had CR, for an ORR of 21.6% (Table 2). Among the 21 patients who responded, 11 achieved PR in cycle 2, eight in cycle 4 and two at the end of cycle 6. Median PFS was 4.0 months [95% confidence interval (CI), 3.0–4.9], which was not significantly different from the historical control and the literature [9]. However, median PFS was significantly longer (8.2 months) in 24 patients with grade 2 or higher irAEs such as fever or skin induration at the injection site than in those who had no or grade 1 irAEs (3.1 months; p = 0.003) (Fig. 2). This phenomenon was observed regardless of the presence of visceral metastases or estrogen receptor status. In addition, ORR was higher in this population (36% vs. 16.7%; p = 0.043). Furthermore, median OS was also significantly improved in these patients (25.4 months vs. 16.4 months; p = 0.044) (Fig. 3).


Phase II study of Pseudomonas aeruginosa-Mannose-Sensitive hemagglutinin in combination with capecitabine for Her-2-negative metastatic breast cancer pretreated with anthracycline and taxane.

Lv F, Cao J, Liu Z, Wang Z, Zhang J, Zhang S, Wang L, Zhao X, Shao Z, Wang B, Hu X - PLoS ONE (2015)

PFS curve of patients with different grades of irAEs.Patients with grade 2 or higher irAEs (N = 24, events 20) had longer PFS than those who had no or grade 1 irAEs (N = 69, events 63) (p = 0.003).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359133&req=5

pone.0118607.g002: PFS curve of patients with different grades of irAEs.Patients with grade 2 or higher irAEs (N = 24, events 20) had longer PFS than those who had no or grade 1 irAEs (N = 69, events 63) (p = 0.003).
Mentions: After a median follow-up of 22 months, 83 (85.6%) patients had disease progression and 38 (39.2%) patients had died. Twenty-one patients achieved PR and no patient had CR, for an ORR of 21.6% (Table 2). Among the 21 patients who responded, 11 achieved PR in cycle 2, eight in cycle 4 and two at the end of cycle 6. Median PFS was 4.0 months [95% confidence interval (CI), 3.0–4.9], which was not significantly different from the historical control and the literature [9]. However, median PFS was significantly longer (8.2 months) in 24 patients with grade 2 or higher irAEs such as fever or skin induration at the injection site than in those who had no or grade 1 irAEs (3.1 months; p = 0.003) (Fig. 2). This phenomenon was observed regardless of the presence of visceral metastases or estrogen receptor status. In addition, ORR was higher in this population (36% vs. 16.7%; p = 0.043). Furthermore, median OS was also significantly improved in these patients (25.4 months vs. 16.4 months; p = 0.044) (Fig. 3).

Bottom Line: PA-MSHA has a good safety profile, with only 6 patients (6.2 %) discontinuing treatment.PA-MSHA did not increase capecitabine-related toxicities such as hand-foot syndrome, nausea, and vomiting.Adding PA-MSHA to capecitabine has a good safety profile in patients with heavily pre-treated MBC, although benefit from this regimen might occur only in patients with moderate PA-MSHA-related adverse events.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

ABSTRACT

Purpose: Metastatic breast cancer (MBC) remains an incurable disease despite major therapeutic advances. Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) has been established to have anti-proliferative effects against breast cancer cells in preclinical experiments, and is indicated for treatment of cancer in China. We performed a phase II trial combining PA-MSHA with capecitabine in patients with heavily pretreated MBC.

Methods: Eligibility criteria included human epidermal growth factor receptor 2-negative MBC, prior therapy with anthracyclines and taxanes, at least one prior chemotherapy regimen for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. PA-MSHA 1 mg was administered subcutaneously every other day and capecitabine 1000 mg/m2 orally twice a day for 2 weeks on, 1 week off. The primary end point was progression-free survival.

Results: A total of 97 patients were enrolled. Median progression-free survival (PFS) was 4.0 months [95 % confidence interval (CI) 3.0-4.9], which was not significantly different from that in historical controls. However, median PFS was significantly longer (8.2 months; 95 % CI 6.7-9.7) in 24 patients with moderate immune-related adverse events (irAEs) such as fever or skin induration at the injection site than in those with no or mild irAEs (3.1 months, 95 % CI 2.5-3.6; p = 0.003). Overall survival was also improved in these patients (25.4 vs. 16.4 months; p = 0.044). PA-MSHA has a good safety profile, with only 6 patients (6.2 %) discontinuing treatment. PA-MSHA did not increase capecitabine-related toxicities such as hand-foot syndrome, nausea, and vomiting.

Conclusion: Adding PA-MSHA to capecitabine has a good safety profile in patients with heavily pre-treated MBC, although benefit from this regimen might occur only in patients with moderate PA-MSHA-related adverse events.

Trial registration: ClinicalTrials.gov NCT01380808.

No MeSH data available.


Related in: MedlinePlus