Lobaplatin-based neoadjuvant chemotherapy for triple-negative breast cancer: a 5-year follow-up of a randomized, open-label, phase II trial

Abstract

Purpose: We report the 5-year follow-up findings of a randomized, open-label, phase II trial of lobaplatin-based neoadjuvant chemotherapy plus adjuvant therapy for triple-negative breast cancer (TNBC). Patients and methods: This study included patients aged ⩾18 years with untreated, operable stage I–III TNBC and an Eastern Cooperative Oncology Group performance status of 0 or 1. One group of patients (TE group, n = 99) received four cycles of docetaxel (T, 75 mg/m²) plus epirubicin (E, 80 mg/m²) every 3 weeks, and another group (TEL group, n = 101) received the same treatment with the addition of lobaplatin (L, 30 mg/m2). Two cycles of the corresponding treatments were administered after surgery in both groups. The primary endpoints were total pathological complete response (tpCR) rate and overall response rate (ORR), and the secondary endpoints were disease-free survival, overall survival, and long-term safety. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-14005019). Results: The median follow-up was 48.2 months (interquartile range: 31.1–60.0). The tpCR rate was 41.4% and 17.8% in the TEL group and TE group, respectively ( p < 0.001). The HR for comparison of DFS between the TEL group and TE group was 0.44 (95% CI: 0.21–0.90, P p = 0.028). The addition of lobaplatin resulted in an HR of 0.44 (95% CI: 0.18–1.02, P = 0.061) for the difference in OS between the two groups. The ORR, which included complete response and partial response, was 92.9% in the TEL group and 74.3% in the TE group ( p = 0.001). The TEL group patients were more likely to develop grade III–IV anemia and thrombocytopenia. No lobaplatin-related deaths or increased risk of long-term toxicity was observed. Conclusion: Neoadjuvant lobaplatin therapy can improve the tpCR and ORR rates of TNBC with tolerable side effects and have a tendency to improve the long-term survival.

Taxane combined with lobaplatin or anthracycline for neoadjuvant chemotherapy of triple-negative breast cancer: a randomized, controlled, phase II study

“…This is expected to be the case in our current practice as well, although the current data is immature, and long-term follow-up is needed. As for toxicity, in combination with the results of the current study and two previous studies conducted by our team on lobaplatin, we hypothesize that, compared to the regimen of taxane plus anthracycline, the TL regimen increases the risk of grade-3/4 anemia, but decreases the risk of grade-3/4 neutropenia [8,9]. There are some limitations to this clinical trial.…”

“…As we previously reported in a phase-II clinical trial and 5-year follow-up study, the addition of lobaplatin to taxane and anthracycline was found to significantly improve overall pathologic and objective response rates and DFS. [8,9]. A phase II study compared the efficacy and toxicity of TL (docetaxel + lobaplatin) induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy and TPF (docetaxel + cisplatin + 5-fluorouracil) induction chemotherapy combined with cisplatin concurrent chemoradiotherapy in the treatment of locally advanced head and neck squamous cell carcinoma, and the results indicated that patients survived longer and experienced lower toxicity when treated with TL regimen [10].…”

Lobaplatin induces apoptosis in T24 and 5637 bladder cancer cells by regulating Bcl-2 and Bax expression and inhibiting the PI3K/Akt signaling pathway

“…Lobaplatin (LBP), a third-generation platinum-based drug only available in the Chinese market, has been approved for treating metastatic BC, chronic granulocytic leukemia, and small cell lung cancer ( 5 ), for which surgical removal is not an option. In addition, some studies have confirmed that LBP is effective in treating other cancer types, including cervical cancer, triple-negative breast cancer, primary hepatocellular carcinoma, and T4 gastric cancer ( 6 - 9 ). Compared to other platinum-based chemotherapy drugs on the market, such as cisplatin (DDP), LBP is less toxic to the kidney, nerves and ear and bypasses the DDP resistance of cancer cells ( 10 ).…”

Safety and efficacy of anlotinib combined with taxane and lobaplatin in neoadjuvant treatment of clinical stage II/III triple-negative breast cancer in China (the neoALTAL trial): a single-arm, phase 2 trial

“… 6 In addition, a phase II randomized controlled clinical study of our group showed that neoadjuvant therapy with LBP can improve the pCR and ORR rates of TNBC, with tolerable side effects and a trend towards improving long-term survival. 7 , 8 …”