Platinum combination therapy gives hope to breast cancer patients

Platinum combination therapy gives hope to breast cancer patients

14 Apr 2015

The preoperative combination of gemcitabine, carboplatin, and iniparib is active and well tolerated in the treatment of early-stage triple negative breast cancer (TNBC) and BRCA1/2 mutation-associated breast cancer, finds a new study.

As sporadic TNBC shares many pathologic and molecular features with breast cancer caused by hereditary BRCA1 germline mutations, scientists were led to the hypothesis that sporadic TNBC may possess similar DNA repair defects and similar chemo sensitivity profiles to BRCA1/2 mutation.

Study design

Consequently, Melinda Telli and colleagues, from Stanford University School of Medicine, set out to investigate a neoadjuvant combination chemotherapy regimen (gemcitabine, carboplatin, and iniparib) targeting DNA repair defects in early-stage TNBC and BRCA1 /2 mutation associated breast cancer.

In the phase 2 neoadjuvant study, 93 patients with stage I to IIIA estrogen receptor-negative or BRCA1/2 mutation-associated breast cancer received intravenous (IV) neoadjuvant gemcitabine IV carboplatin and IV iniparib. The primary endpoint was pathologic complete response. The protocol was administered every 21 days for four cycles, but was later amended to six cycles. Altogether 80 patients received six cycles.

Clinical outcomes with measurable adverse events

After analysis, the results showed that:

• The overall pathologic complete response in the intent-to-treat population was 36%.
• Additionally, mean HRD-LOH scores were higher in responders compared with non responders and remained significant when BRCA1/2 germline mutations carriers were excluded.

The most common adverse events for those treated were fatigue, nausea and neutropenia or neutrophil count decreases.

 “Our results do not have direct impact on clinical practice today, but they strongly suggest that patient selection based on underlying DNA repair deficiency in future randomized trials of standard versus DNA repair defect-targeted therapy in TNBC should be pursued,” write the authors.

Source: eCancer News