Evaluating the long-term effectiveness and safety of adding carboplatin with or without veliparib to standard chemotherapy given before surgery in patients with triple‑negative breast cancer.

This study reported the long-term effectiveness and safety of adding carboplatin (Paraplatin) with or without veliparib (ABT-888) to standard chemotherapy given before surgery (neoadjuvant chemotherapy; NACT) in patients with early-stage triple-negative breast cancer (TNBC). The data showed that the addition of carboplatin to standard NACT was associated with a long-term survival benefit without increasing the risk of second cancers in these patients.

TNBC is a subtype of BC that tests negative for female hormone receptors (estrogen and/or progesterone) and the HER2 protein. BRCA1 and BRCA2 gene mutations (abnormalities) can be found in many patients with breast cancer. BRCA1/BRCA2 genes block the rapid and uncontrolled growth of cells, therefore the formation of tumors. These mutations are often found in young patients and can be very resistant to current treatment options. Targeted therapy is an option for these patients.

Veliparib is a targeted therapy that blocks a protein called PARP, which helps damaged cells to repair themselves. Therefore, PARP inhibitors keep cancer cells from repairing themselves which eventually causes them to die.

Neoadjuvant chemotherapy (NACT; treatment before surgery) is often given before surgery to shrink the cancer so that it can be completely destroyed by surgery. Platinum-based agents such as carboplatin are chemotherapy drugs that damage the DNA in cancer cells, causing the cells to die. Previous studies have shown that adding carboplatin with or without veliparib to NACT improves the pathological complete response (pCR; the absence of any cancer cells after surgery) rate for patients with TNBC. However, the long-term effectiveness and safety outcomes of adding carboplatin with or without veliparib to standard NACT for the treatment of patients with early-stage TNBC are still unknown.

This study involved 634 patients with untreated stage II-III TNBC. Patients were randomly assigned into 3 groups. Group 1 included 316 patients who received carboplatin plus veliparib with paclitaxel. Group 2 included 160 patients who received carboplatin plus paclitaxel. Group 3 included 158 patients who received paclitaxel alone. The average follow-up time was 4.5 years.

Patients in group 1 were 37% more likely to survive without any cancer events compared to patients in group 3. No significant difference in survival benefit was observed between patients in group 1 and patients in group 2. After 4 years, 78% of the patients were alive in group 1, 79% were alive in group 2 and 69% were alive in group 3.

The overall survival rates were not significantly different between the 3 treatment groups. The rates of myelodysplastic syndromes (a blood cancer where the bone marrow does not make enough healthy mature blood cells), acute myeloid leukemia (cancer of the blood and bone marrow), or other secondary cancers were also similar between the 3 treatment groups.

This study concluded that the addition of carboplatin to standard NACT was associated with a long-term survival benefit without increasing the risk of second cancers in patients with early-stage TNBC. The addition of veliparib to carboplatin and standard NACT did not impact survival compared to carboplatin and standard NACT in these patients. 

This study was sponsored by AbbVie, the manufacturer of veliparib.