There was a response rate of 77.8 percent when patients with advanced BRCA-positive breast cancer added the PARP inhibitor veliparib to carboplatin/paclitaxel chemotherapy, according to findings from the phase 2 BROCADE trial.
“The addition of veliparib to carboplatin/paclitaxel resulted in trends toward improved progression-free survival (PFS) and overall survival (OS) and a significant increase in the overall response rate (ORR),” lead study author Hyo Sook Han, M.D., associate member at Moffitt Cancer Center, said when presenting the results at the 2016 San Antonio Breast Cancer Symposium.
The phase 2 BROCADE study included 290 women with histologically or cytologically confirmed locally recurrent or metastatic breast cancer who harbored a deleterious BRCA1 or BRCA2 germline mutation. Patients were allowed to have received two or fewer prior lines of chemotherapy in the metastatic setting. Individuals with prior PARP inhibitor treatment or CNS metastases were ineligible.
The three-arm trial randomized patients in a 1-1-1 ratio to veliparib (120 mg twice daily on days one through seven) plus carboplatin (AUC 6)/paclitaxel (175 mg/m2) every three weeks (97 patients); the same chemotherapy regimen plus placebo (99 patients); or veliparib (40 mg twice daily on days one through seven) plus temozolomide (150-200 mg/m2 each day on days one through five) every four weeks (94 patients).
Han reported the findings for the first two arms at the press briefing. In the placebo arm, the median patient age was 46 years (range, 24-66). Regarding hormone receptor status, 43.4 percent of patients were ER/PgR-negative and 56.6 percent of patients were ER and/or PgR-positive.
HER2neu-negative status was reported for 92.9 percent of patients and 42.4 percent of patients had triple-negative disease. The ECOG performance status was 0-1 for 93.9 percent of patients. The number of prior treatments received across all settings was zero, one, two or more than two, for 23.2 percent, 42.4 percent, 25.3 percent, and 9.1 percent of patients.
In the veliparib arm, the median patient age was 44 years (range, 25-65). The hormone receptor status was ER/PgR-negative for 41.2 percent of patients and ER and/or PgR-positive for 58.8 percent of patients.
HER2neu-negative status was reported for 96.9 percent of patients and 41.2 percent of patients had triple-negative disease. The ECOG performance status was 0-1 for 94.8 percent of patients. The number of prior treatments received across all settings was zero, one, two or more than two, for 19.6 percent, 48.5 percent, 24.7 percent, and 7.2 percent of patients.
Tumor response was assessed in patients with measurable disease, which included 72 patients in the veliparib arm and 80 patients in the placebo arm. The overall response rate was 77.8 percent in the veliparib arm and 61.3 percent in the placebo group.
The complete and partial response rates in the veliparib versus placebo arms were 5.6 percent (four patients) versus 3.8 percent (three patients) and 72.2 percent (52 patients) versus 57.5 percent (46 patients), respectively. The clinical benefit rate (progression-free rate at 18 weeks) was 90.7 percent versus 87.0 percent, respectively. The median duration of response was 11.7 months in the veliparib arm and 11.1 months in the placebo arm.
The median PFS was 14.1 months for the veliparib arm and 12.3 months for the placebo group.
The median OS was 28.3 months versus 25.9 months with veliparib versus placebo, respectively. The OS data are not fully mature yet.
“The safety profile of veliparib plus carboplatin/paclitaxel was comparable to that of carboplatin/paclitaxel alone,” said Han. All-grade adverse events (AEs) occurred in 100 percent of the veliparib arm and 97.9 percent of the placebo arm.
The most common nonhematologic AEs in the veliparib versus the placebo arm included alopecia (66.7 percent vs 57.3 percent), arthralgia (36.6 percent vs 32.3 percent), back pain (30.1 percent vs 22.9 percent), constipation (38.7 percent vs 29.2 percent), diarrhea (38.7 percent vs 28.1 percent), fatigue (50.5 percent vs 59.4 percent), headache (35.5 percent vs 32.3 percent) and peripheral neuropathy (68.8 percent vs 59.4 percent).
Common hematologic malignancies included anemia (57 percent with veliparib versus 51 percent with placebo), leukopenia (30.1 percent vs 28.1 percent), neutropenia (74.2 percent vs 74 percent) and thrombocytopenia (71 percent vs 69.8 percent).
Serious AEs occurred in 34.4 percent and 27.1 percent of the veliparib and placebo arms, respectively. Grade 3/4 AEs occurred in 78.5 percent and 83.3 percent of the 2 arms, respectively. The most common hematologic grade 3/4 AEs included anemia (17.2 percent vs 17.7 percent), febrile neutropenia (8.6 percent vs 3.1 percent), leukopenia (16.1 percent vs 11.5 percent), neutropenia (55.9 percent vs 55.2 percent) and thrombocytopenia (31.2 percent vs 26 percent). The most frequently reported nonhematologic grade 3/4 AEs were diarrhea (4.3 percent vs 7.3 percent), drug hypersensitivity (5.4 percent vs 0), fatigue (5.4 percent vs 8.3 percent) and peripheral neuropathy (7.5 percent vs 5.2 percent).
“The addition of veliparib did not increase the frequency of interruption, dose reduction, or discontinuation of veliparib/placebo, carboplatin, or paclitaxel due to adverse events,” said Han.
The results from the temozolomide arm will be presented later at the meeting. Han noted, however, that, the data suggest that the veliparib/temozolomide regimen is inferior compared with the carboplatin/paclitaxel-alone arm.
“Further evaluation of the efficacy and safety of veliparib with weekly paclitaxel and carboplatin in patients with BRCA-mutated advanced breast cancer is ongoing in the phase 3 randomized trial BROCADE3 (NCT02163694),” Han said in her concluding remarks.