Carboplatin Adds No Benefit to Standard Therapy for Basal-Like Breast Cancer

CHICAGO – Adding carboplatin to standard chemotherapy for patients with basal-like breast cancer neither increased toxicity of the regimen nor improved its efficacy, reported investigators at the annual meeting of the American Society of Clinical Oncology.

Patients who were randomized to receive epirubicin and cyclophosphamide followed by docetaxel (Taxotere) and carboplatin had a pathologically confirmed complete response (pCR) rate of 30%, compared with 35% for patients who were assigned to a similar regimen without the platinum compound (P = .6064).

Mastectomy rates were also similar between the groups, at 28% and 33%, respectively, reported Dr. Emilio Alba from Hospital Universitario Virgen de la Victoria in Malaga, Spain, and colleagues in the Spanish Breast Cancer Research Group (GEICAM).

The rationale for adding carboplatin to a standard chemotherapy regimen is that basal-like breast cancer and the genetically similar triple-negative breast cancer subtypes are known to be sensitive to DNA-damaging agents such as alkylators, anthracyclines, and – theoretically – platinum compounds. But the patients in the study had already been exposed to an anthracycline (epirubicin), which may explain the lack of efficacy of a second DNA-damaging agent, the investigators speculated.

"Do we know whether a platinum compound is necessary for the efficacy? There are many other potential agents under investigation, including a PARP [poly (ADP [adenosine diphosphate]–ribose) polymerase] inhibitor, and we don’t really know what the molecular signature is to predict the benefit of adding another toxin," said Dr. George Somlo of the City of Hope Cancer Center in Duarte, Calif., who commented on the study in a poster discussion session.

He added that there are data to suggest that paclitaxel may be a better partner than docetaxel in this population.

The GEICAM investigators enrolled women with tumors 2 cm in diameter or greater (smaller tumors were allowed if axillary nodes were positive) and basal-like disease by immunophenotype (negative for the estrogen receptor, progesterone receptor, and HER2, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor).

The patients were randomly assigned to receive either epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² for four cycles, followed by either docetaxel 100 mg/m² for four cycles, or docetaxel 75 mg/m² plus carboplatin to an area-under-the-curve dose of 6 mL/min for four cycles. In all, 46 patients were assigned to standard therapy, and 47 to the carboplatin arm.

The primary end point was pCR measured by Miller and Payne criteria. Secondary end points included clinical response, toxicity, type of surgery, and axillary status at surgery.

In an intention-to-treat analysis, the overall response rate was 72% in the standard arm and 79% in the carboplatin arm. The pCRs in the breast and axilla combined were 30% in each arm.

Grade 3/4 toxicities were generally similar between the treatment groups, with neutropenia, febrile neutropenia, fatigue, infection, and vomiting more frequent in the standard therapy arm; and hemoglobinemia, leukocytopenia, nausea and syncope more frequent in the carboplatin group.

The authors recommend that "the findings from this trial should be taken into account in the future development of PARP inhibitors."

The study was supported by the GEICAM. The authors had no disclosures.

CHICAGO – Adding carboplatin to standard chemotherapy for patients with basal-like breast cancer neither increased toxicity of the regimen nor improved its efficacy, reported investigators at the annual meeting of the American Society of Clinical Oncology.

Patients who were randomized to receive epirubicin and cyclophosphamide followed by docetaxel (Taxotere) and carboplatin had a pathologically confirmed complete response (pCR) rate of 30%, compared with 35% for patients who were assigned to a similar regimen without the platinum compound (P = .6064).

Mastectomy rates were also similar between the groups, at 28% and 33%, respectively, reported Dr. Emilio Alba from Hospital Universitario Virgen de la Victoria in Malaga, Spain, and colleagues in the Spanish Breast Cancer Research Group (GEICAM).

The rationale for adding carboplatin to a standard chemotherapy regimen is that basal-like breast cancer and the genetically similar triple-negative breast cancer subtypes are known to be sensitive to DNA-damaging agents such as alkylators, anthracyclines, and – theoretically – platinum compounds. But the patients in the study had already been exposed to an anthracycline (epirubicin), which may explain the lack of efficacy of a second DNA-damaging agent, the investigators speculated.

"Do we know whether a platinum compound is necessary for the efficacy? There are many other potential agents under investigation, including a PARP [poly (ADP [adenosine diphosphate]–ribose) polymerase] inhibitor, and we don’t really know what the molecular signature is to predict the benefit of adding another toxin," said Dr. George Somlo of the City of Hope Cancer Center in Duarte, Calif., who commented on the study in a poster discussion session.

He added that there are data to suggest that paclitaxel may be a better partner than docetaxel in this population.

The GEICAM investigators enrolled women with tumors 2 cm in diameter or greater (smaller tumors were allowed if axillary nodes were positive) and basal-like disease by immunophenotype (negative for the estrogen receptor, progesterone receptor, and HER2, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor).

The patients were randomly assigned to receive either epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² for four cycles, followed by either docetaxel 100 mg/m² for four cycles, or docetaxel 75 mg/m² plus carboplatin to an area-under-the-curve dose of 6 mL/min for four cycles. In all, 46 patients were assigned to standard therapy, and 47 to the carboplatin arm.

The primary end point was pCR measured by Miller and Payne criteria. Secondary end points included clinical response, toxicity, type of surgery, and axillary status at surgery.

In an intention-to-treat analysis, the overall response rate was 72% in the standard arm and 79% in the carboplatin arm. The pCRs in the breast and axilla combined were 30% in each arm.

Grade 3/4 toxicities were generally similar between the treatment groups, with neutropenia, febrile neutropenia, fatigue, infection, and vomiting more frequent in the standard therapy arm; and hemoglobinemia, leukocytopenia, nausea and syncope more frequent in the carboplatin group.

The authors recommend that "the findings from this trial should be taken into account in the future development of PARP inhibitors."

The study was supported by the GEICAM. The authors had no disclosures.

CHICAGO – Adding carboplatin to standard chemotherapy for patients with basal-like breast cancer neither increased toxicity of the regimen nor improved its efficacy, reported investigators at the annual meeting of the American Society of Clinical Oncology.

Patients who were randomized to receive epirubicin and cyclophosphamide followed by docetaxel (Taxotere) and carboplatin had a pathologically confirmed complete response (pCR) rate of 30%, compared with 35% for patients who were assigned to a similar regimen without the platinum compound (P = .6064).

Mastectomy rates were also similar between the groups, at 28% and 33%, respectively, reported Dr. Emilio Alba from Hospital Universitario Virgen de la Victoria in Malaga, Spain, and colleagues in the Spanish Breast Cancer Research Group (GEICAM).

The rationale for adding carboplatin to a standard chemotherapy regimen is that basal-like breast cancer and the genetically similar triple-negative breast cancer subtypes are known to be sensitive to DNA-damaging agents such as alkylators, anthracyclines, and – theoretically – platinum compounds. But the patients in the study had already been exposed to an anthracycline (epirubicin), which may explain the lack of efficacy of a second DNA-damaging agent, the investigators speculated.

"Do we know whether a platinum compound is necessary for the efficacy? There are many other potential agents under investigation, including a PARP [poly (ADP [adenosine diphosphate]–ribose) polymerase] inhibitor, and we don’t really know what the molecular signature is to predict the benefit of adding another toxin," said Dr. George Somlo of the City of Hope Cancer Center in Duarte, Calif., who commented on the study in a poster discussion session.

He added that there are data to suggest that paclitaxel may be a better partner than docetaxel in this population.

The GEICAM investigators enrolled women with tumors 2 cm in diameter or greater (smaller tumors were allowed if axillary nodes were positive) and basal-like disease by immunophenotype (negative for the estrogen receptor, progesterone receptor, and HER2, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor).

The patients were randomly assigned to receive either epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² for four cycles, followed by either docetaxel 100 mg/m² for four cycles, or docetaxel 75 mg/m² plus carboplatin to an area-under-the-curve dose of 6 mL/min for four cycles. In all, 46 patients were assigned to standard therapy, and 47 to the carboplatin arm.

The primary end point was pCR measured by Miller and Payne criteria. Secondary end points included clinical response, toxicity, type of surgery, and axillary status at surgery.

In an intention-to-treat analysis, the overall response rate was 72% in the standard arm and 79% in the carboplatin arm. The pCRs in the breast and axilla combined were 30% in each arm.

Grade 3/4 toxicities were generally similar between the treatment groups, with neutropenia, febrile neutropenia, fatigue, infection, and vomiting more frequent in the standard therapy arm; and hemoglobinemia, leukocytopenia, nausea and syncope more frequent in the carboplatin group.

The authors recommend that "the findings from this trial should be taken into account in the future development of PARP inhibitors."

The study was supported by the GEICAM. The authors had no disclosures.