仿制与原研培美曲塞治疗非小细胞肺癌疗效与安全性的比较研究

Comparative study on efficacy and safety of generic and original pemetrexed in patients with non-small cell lung cancer

目的比较首批城市药品集中带量采购中标的四川汇宇制药股份有限公司生产的培美曲塞(仿制药)与Eli Lilly Nederland B.V.生产的培美曲塞(原研药)治疗非小细胞肺癌(NSCLC)的疗效与安全性。方法以2019年3—12月在中国医学科学院北京协和医学院肿瘤医院使用仿制和原研培美曲塞治疗的NSCLC患者为研究对象,收集患者人口学特征(年龄、性别、既往史等)、治疗相关信息(NSCLC分期、治疗方案、合并疾病等)、不良事件发生情况及疗效评价等信息。将患者分为仿制药组和原研药组,比较2组患者的一般情况、培美曲塞的临床使用情况及不良事件发生情况。对2组患者性别、年龄、体重、体表面积、美国东部肿瘤协作组(ECOG)评分、肿瘤分期、标准化疗剂量等7个指标进行倾向性评分匹配后,比较2组患者使用培美曲塞2个周期后的疗效与安全性。结果纳入研究的患者共182例,仿制药组85例,原研药组97例。2组患者在年龄、性别、ECOG评分、体重及体表面积、合并慢性疾病方面差异均无统计学意义(P>0.05)。仿制药组晚期患者(Ⅲ、Ⅳ期)明显多于原研药组[92%(78/85)比79%(77/97),P=0.032],采用姑息化疗和维持化疗者占比高于原研药组(P<0.001),中位给药剂量高于原研药组[900(800,1000)mg/m^(2)比800(800,900)mg/m^(2),P=0.019],中位化疗周期数多于原研药组[5(4,10)个比4(2,4)个,P<0.001],不良事件总发生率、骨髓毒性反应和肝毒性反应的发生率均高于原研药组(P=0.018,P=0.037,P=0.018)。进行倾向性评分匹配后,仿制药组和原研药组患者均为38例,客观缓解率、疾病控制率和不良事件发生率比较差异均无统计学意义[26%(10/38)比32%(12/38),P=0.723;89%(34/38)比96%(36/38),P=0.674;47%(18/38)比24%(9/38),P=0.055]。结论采用倾向性评分匹配后,仿制与原研培美曲塞治疗NSCLC的疗效与安全性没有明显差异。

Objective To compare the efficacy and safety between the generic pemetrexed produced by Sichuan Huiyu Pharmaceutical Co.,LTD and the original pemetrexed produced by Eli Lilly Nederland B.V.in the treatment for patients with non-small cell lung cancer(NSCLC).Methods The subjects were patients who received generic and original pemetrexed from March 2019 to December 2019 in Cancer Hospital of Chinese Academy of Medical Sciences.Demographic characteristics(age,gender,past history,etc.),treatment-related information(NSCLC stage,treatment regimen,underlying diseases,etc.),occurrence of adverse events,and efficacy evaluation in patients were collected.Patients were divided into the generic group and the original group,and the general situation,clinical use of pemetrexed,and adverse events in patients in the 2 groups were compared.After propensity score matching for 7 variables such as gender,age,body weight,body surface area,Eastern Cooperative Oncology Group(ECOG)score,tumor stage,and standardized chemotherapy dose,the efficacy and safety in patients between the 2 groups after 2 cycles of treatment with generic and original pemetrexed were compared.Results A total of 182 patients were enrolled in the study,including 85 patients in the generic group and 97 patients in the original group.The differences in age,gender,ECOG score,body weight and body surface area,and underlying chronic diseases between the 2 groups were not statistically significant(all P>0.05).The patients with advanced stageⅢandⅣcancer in the generic group were significantly more than those in the original group[92%(78/85)vs.79%(77/97),P=0.032].The proportion of palliative chemotherapy and maintenance chemotherapy in the generic group was higher than that in the original group(P<0.001).The difference in median dosage between the generic group and the original group was statistically significant[900(800,1000)mg/m^(2)vs.800(800,900)mg/m^(2),P=0.019].The difference in chemotherapy cycles between the 2 groups was statistically significant[5(4,10)vs.4(2,4),P<0.001].The overall incidence of adverse events and the incidences of bone marrow toxicity and liver toxicity in the generic group were higher than those in the original group(P=0.018,P=0.037,P=0.018).After propensity score matching,there were 38 patients in both groups,and the differences in the objective response rate,disease control rate and the incidence of adverse events between the 2 groups were not statistically significant[26%(10/38)vs.32%(12/38),P=0.723;89%(34/38)vs.96%(36/38),P=0.674;47%(18/38)vs.24%(9/38),P=0.055].Conclusion After propensity score matching,the difference in the efficacy and safety between the generic and the original pemetrexed was not significant.