Clinical Efficacy of Pyrotinib Combined with Capecitabine in the Second-Line or Above Treatment for HER-2 Positive Advanced Breast Cancer and Its Association with Cell-Free DNA

PURPOSE: To evaluate the clinical efficacy of pyrotinib combined with capecitabine in the treatment of HER-2 positive breast cancer in real world and its correlation with cfDNA. METHODS: From September 2020 to June 2021, 181 cases of HER-2 positive advanced breast cancer patients who were treated in Jiangsu Cancer Hospital and Nantong Cancer Hospital were analyzed. Patients were given pyrotinib combined with capecitabine or trastuzumab combined with capecitabine. Eighty-one patients who received pyrotinib+capecitabine second-line or above treatment were included in the pyrotinib group, and 100 patients who received trastuzumab+capecitabine second-line or above treatment were included in the trastuzumab group. The objective response rate (ORR) and clinical benefit rate (CBR) of the two groups were compared. The follow-up results of the patients were analyzed, and the progression-free survival (PFS) and adverse reactions were compared between the two groups. Plasma cfDNA was detected by real-time fluorescence quantitative PCR. The cfDNA levels of patients before and after treatment were compared, and the change of cfDNA levels in patients with different curative effects over time was recorded. The patients were further divided into high cfDNA expression and low cfDNA expression groups, and the PFS of patients with different cfDNA levels was analyzed. COX univariate and multivariate analysis of factors influencing posttreatment survival in patients with HER-2-positive breast cancer were performed. RESULTS: The ORR of the pyrotinib group (58.02%) was significantly higher than that of the trastuzumab group (42.00%, P = 0.0369). Similarly, the CBR of the pyrotinib group (65.43%) was significantly higher than that of the trastuzumab group (49.00%, P = 0.0347). The incidence of adverse reactions between the two groups was not statistically significant (P > 0.05). The results of survival analysis showed that the PFS of the pyrotinib group was 8.02 ± 3.05 months, the PFS of the trastuzumab group was 7.11 ± 3.06 months, and the PFS of the pyrotinib group was significantly longer than that of the trastuzumab group (P = 0.035). The comparison of cfDNA levels between the two groups showed that on the 28th and 56th day of treatment, the cfDNA levels in the pyrotinib group were significantly lower than those in the trastuzumab group (P < 0.05). Long-term follow-up results showed that compared with patients with high cfDNA expression, the PFS of patients with low cfDNA expression was significantly prolonged (P < 0.05). The level of cfDNA is an independent risk factor affecting the prognosis of patients with HER-2-positive breast cancer. CONCLUSION: The combined use of pyrotinib and capecitabine has good clinical efficacy and high safety in patients with HER-2 positive breast cancer. The combined use of pyrotinib and capecitabine prolongs the PFS of patients and reduces the level of plasma cfDNA. Changes in cfDNA levels can reflect the therapeutic efficacy of patients with HER-2-positive breast cancer to a certain extent and can be used as a potential indicator for evaluating the prognosis of patients with HER-2-positive breast cancer.