Clinical efficacy of afatinib in second-line treatment of advanced squamous cell carcinoma of the lung
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摘要:
目的 观察阿法替尼在晚期肺鳞癌患者二线治疗中的疗效及不良反应，探讨其临床应用价值。 方法 收集蚌埠医科大学第一附属医院2020年3月—2022年10月驱动基因阴性的晚期肺鳞癌患者58例，按指南予以阿法替尼40 mg/d，口服，发生3级以上副反应时，停药至患者恢复，重新用药剂量按10 mg/次下调，最低至20 mg/d。按实体瘤疗效评价标准1.1版每6周评价1次，至疾病进展，观察疗效及不良反应。 结果 (1) 临床疗效：完全缓解0例，部分缓解20例(34.48%)，稳定18例(31.04%)，疾病进展20例(34.48%)，客观缓解率(ORR)为34.48%，疾病控制率(DCR)为65.52%；中位无进展生存期(mPFS)为4.20个月(95% CI: 3.62~4.78)，中位总生存期(mOS)为11.60个月(95% CI: 7.99~15.21)。(2)单因素分析显示：体力状况评分(PS)、基础疾病与DCR、mPFS及mOS均有相关性，非敏感基因突变、远处转移与mPFS、mOS均有相关性(P＜0.05)。(3)多因素分析显示：PS评分、基础疾病是mPFS、mOS的影响因素(P＜0.05)。(4)不良反应：腹泻58例(100.00%)、皮疹44例(75.86%)，3级不良反应中腹泻7例(12.07%)、皮疹5例(8.62%)，无3级以上不良事件。 结论 阿法替尼是晚期肺鳞癌患者二线治疗的可选择方案，疗效好，不良反应可控。 Abstract:Objective To observe the efficacy and adverse reactions of afatinib in the second-line treatment of patients with advanced lung squamous cell carcinoma, and to explore the clinical value. Methods A total of 58 patients with advanced lung squamoma with negative driver genes were collected from the First Affiliated Hospital of Bengbu Medical University from March 2020 to October 2022 and afatinib was given orally at 40 mg/d according to the guidelines. When grade 3 or more side reactions occurred, the drug was stopped until the patients recovered, and the dose of re-administration was reduced by 10 mg/time to the lowest 20 mg/d. The patients were evaluated every 6 weeks according to response evaluation criteria in solid tumor 1.1 until the disease progressed, and the therapeutic efficacy and adverse effects were observed. Results (1) Clinical efficacy: 0 cases of complete remission, 20 cases of partial remission (34.48%), 18 cases of stable disease (31.04%), 20 cases of progressive disease (34.48%), objective response rate (ORR) was 34.48%, disease control rate (DCR) 65.52%; The median progression-free survival (mPFS) was 4.20 months (95% CI: 3.62-4.78) and the median overall survival (mOS) was 11.60 months (95% CI: 7.99-15.21). (2) Univariate results showed that PS score and underlying diseases were correlated with DCR, mPFS, and mOS, while non-sensitive gene mutation and distant metastasis were correlated with mPFS and mOS, and the differences were statistically significant (P < 0.05). (3) Multiple factors showed that PS score and underlying disease were risk factors for mPFS and mOS, and the differences were statistically significant (P < 0.05). (4) Adverse reactions: diarrhea in 58 cases (100.00%), skin rash in 44 cases (75.86%), and grade 3 adverse reactions, diarrhea in 7 cases (12.07%), skin rash in 5 cases (8.62%), no grade 3 or above adverse events. Conclusion Afatinib is an alternative second-line treatment for patients with advanced lung squamous cell carcinoma, with good efficacy and controllable side effects. -
Key words:
- Lung squamous cell carcinoma /
- Afatinib /
- Targeted therapy /
- Curative effect
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图 1 有无非敏感基因突变患者的mPFS曲线
Figure 1. mPFS curve for patients with non-sensitive gene mutations
图 2 有无远处转移患者的mPFS曲线
Figure 2. mPFS curve of patients with and without distant metastasis
图 4 有无合并基础疾病患者的mPFS曲线
Figure 4. mPFS curve of patients with or without concomitant underlying diseases
图 5 有无非敏感基因突变患者的mOS曲线
Figure 5. mOS curve for patients with non-sensitive gene mutations
图 6 有无远处转移患者的mOS曲线
Figure 6. mOS curve of patients with and without distant metastasis
图 8 有无合并基础疾病患者的mOS曲线
Figure 8. mOS curve of patients with or without concomitant underlying diseases
表 1 影响晚期肺鳞癌患者近期疗效的各亚组分析
Table 1. Analysis of subgroups influencing short-term outcomes in patients with advanced lung squamous cell carcinoma
项目 例数 疗效(例) ORR(%) χ2值 P值 DCR(%) χ2值 P值 PR SD PD 性别 0.102 0.749 0.089 0.765 男性 42 15 13 14 35.71 66.67 女性 16 5 5 6 31.25 62.50 年龄(岁) 0.735a 0.391 0.188a 0.664 ＜65 14 3 5 6 21.43 57.14 ≥65 44 17 13 14 38.64 68.18 吸烟史 0.004 0.952 0.004 0.952 是 20 7 6 7 35.00 65.00 否 38 13 12 13 34.21 65.79 非敏感基因突变 ＜0.001 0.999 0.454 0.500 有 13 4 3 6 30.77 53.85 无 45 16 15 14 35.56 68.89 远处转移 1.221 0.269 1.221 0.269 有 29 8 9 12 27.59 58.62 无 29 12 9 8 41.38 72.41 PS评分(分) 0~1 26 10 11 5 38.46 0.330 0.566 80.77 4.852 0.028 ≥2 32 10 7 15 31.25 53.13 合并基础疾病 有 33 8 9 16 24.24 3.554 0.059 51.52 7.768 0.005 无 25 12 9 4 48.00 84.00 
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表 2 影响晚期肺鳞癌患者mPFS的单因素分析(月)
Table 2. Univariate analysis of mPFS in patients with advanced lung squamous cell carcinoma(months)
项目 例数 mPFS(95% CI) χ2值 P值 性别 0.335 0.563 男性 42 4.50(3.44~5.56) 女性 16 4.00(3.69~4.31) 年龄(岁) 2.655 0.103 ＜65 14 3.50(1.48~5.52) ≥65 44 4.20(3.62~4.79) 吸烟史 0.609 0.435 是 20 3.80(2.49~5.12) 否 38 4.50(3.90~5.10) 非敏感基因突变 4.268 0.039 有 13 4.00(3.38~4.62) 无 45 4.80(3.49~6.11) 远处转移 8.349 0.004 有 29 4.00(3.12~4.88) 无 29 5.00(4.12~5.89) PS评分(分) 10.369 0.001 0~1 26 5.70(4.70~6.70) ≥2 32 3.80(3.17~4.43) 合并基础疾病 12.576 ＜0.001 有 33 3.90(3.58~4.22) 无 25 6.00(3.06~8.94)
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表 3 影响晚期肺鳞癌患者mOS的单因素分析
Table 3. Univariate analysis of mOS in patients with advanced lung squamous cell carcinoma
项目 例数 mOS(95% CI) χ2值 P值 性别 0.072 0.788 男性 42 11.60(8.21~14.99) 女性 16 9.60(4.31~14.89) 年龄(岁) 1.633 0.201 ＜65 14 7.80(5.05~10.55) ≥65 44 12.30(8.86~15.74) 吸烟史 0.034 0.854 是 20 9.40(4.36~14.44) 否 38 11.70(7.62~15.78) 非敏感基因突变 4.482 0.034 有 13 7.90(6.58~9.22) 无 45 12.50(10.94~14.06) 远处转移 5.604 0.018 有 29 8.20(5.56~10.84) 无 29 12.90(12.20~13.60) PS评分(分) 10.105 0.001 0~1 26 14.10(11.51~16.69) ≥2 32 8.20(5.29~11.11) 合并基础疾病 13.939 ＜0.001 有 33 7.90(5.18~10.62) 无 25 14.10(11.65~16.55)
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