Objective: We aimed to evaluate the effect of bevacizumab in the palliative treatment of Chinese metastatic colorectal cancer(mCRC) and its efficacy in different lines. Methods: Patients of mCRC treated with bevacizumab or not at Sun Yat-sen University Cancer Center from 2005 to 2013 were recruited as the study group and control group. The endpoints were objective response rate(ORR), disease control rate(DCR), overall survival(OS) and progression free survival(PFS). The OS and PFS of first-, second- and third-line treatment groups were compared between study group and control group. Results: The median PFS of the study and the control group were 8.2 months(7.0–9.4 months), 5.7 months(4.7–6.6 months), P = 0.001; OS were 26 months(5.4–130.5 months), 18 months(16.6–19.4 months), P < 0.001, respectively. The ORR and DCR of first-, second- and third-line were 30.3%(20/66), 20%(6/30), 17.6%(3/17) and 97%(64/66), 86.7%(26/30), 100%(17/17). In the first-line chemotherapy group, the OS of the study group and the control group were 22.9(5.4–96.7) months and 18(16.6–19.4) months(P < 0.001); PFS were 9.4(8.4–10.4) months and 5.7(4.7–6.6) months(P < 0.001), respectively. While in the second- and third-line setting, only OS were statistically different, PFS had no significant difference. Conclusion: The combination of bevacizumab and chemotherapy had a promising short-term and long-term efficacy in Chinese mCRC patients than those without bevacizumab regimens, and the effect could be better reflected in the first-line treatment.
总生存期(overall survival,OS)是转移性结直肠癌(metastatic colorectal cancer,m CRC)临床试验的主要研究终点,被认为是"金标准"。因为mCRC患者的OS较十年前有明显延长,OS作为临床试验的主要研究终点和评价疗效都受到挑战。在1999年前的单纯化疗时代,无进展生存期(progression-free survival,PFS)被认为是OS的可靠替代终点,由于有效后线治疗的增加,PFS对OS的影响越来越小,其替代性降低;在含靶向药物方案中,尤其是抗血管生成药物治疗中,PFS和OS的相关性也下降。疾病控制时间(duration of disease control,DDC)和治疗策略失败时间(time to failure of strategy,TFS)等新的研究终点逐步显示替代OS的可能性。文章对以上内容进行综述,希望对临床试验的设计和解读提供参考。
Background: It remains controversial whether palliative primary tumor resection(PPTR) can provide survival benefits to the patients with metastatic colorectal cancer(m CRC) who have unresectable metastases. The aim of this study was to evaluate whether PPTR could improve the survival of patients with m CRC.Methods: We conducted a retrospective study on consecutive m CRC patients with unresectable metastases who were diagnosed at Sun Yat?sen University Cancer Center in Guangzhou, Guangdong, China, between January 2005 and December 2012. Overall survival(OS) and progression?free survival(PFS) after first?line chemotherapy failure were compared between the PPTR and non?PPTR patient groups.Results: A total of 387 patients were identified, including 254 who underwent PPTR and 133 who did not. The median OS of the PPTR and non?PPTR groups was 20.8 and 14.8 months(P < 0.001), respectively. The median PFS after first?line chemotherapy was 7.3 and 4.8 months(P < 0.001) in the PPTR and non?PPTR groups, respectively. A larger proportion of patients in the PPTR group(219 of 254, 86.2%) showed local progression compared with that of patients in the non?PPTR group(95 of 133, 71.4%; P < 0.001). Only patients with normal lactate dehydrogenase(LDH) levels and with carcinoembryonic antigen(CEA) levels <70 ng/m L benefited from PPTR(median OS, 22.2 months for the PPTR group and 16.2 months for the non?PPTR group; P < 0.001).Conclusions: For m CRC patients with unresectable metastases, PPTR can improve OS and PFS after first?line chemo?therapy and decrease the incidence of new organ involvement. However, PPTR should be recommended only for patients with normal LDH levels and with CEA levels <70 ng/m L.
