FOLFIRI与西妥昔单抗用于老年转移性结直肠癌患者的一线治疗：CAPRI-GOIM试验中的临床活性与耐受性
Clinical activity and tolerability of FOLFIRI and cetuximab in elderly patients with metastatic colorectal cancer in the CAPRI-GOIM first-line trial.
作者信息
Martinelli E, Cardone C, Troiani T, Normanno N, Pisconti S, Sforza V, Bordonaro A R, Rachiglio A M, Lambiase M, Latiano T P, Modoni G, Cordio S, Giuliani F, Biglietto M, Montesarchio V, Barone C, Tonini G, Cinieri S, Febbraro A, Rizzi D, De Vita F, Orditura M, Colucci G, Maiello E, Ciardiello F, Iaffaioli Vincenzo, Nasti Guglielmo, Nappi Anna, Botti Gerardo, Tatangelo F, Chicchinelli Nicoletta, Montrone Mirko, Sebastio Annamaria, Guarino Tiziana, Simone Gianni, Graziano Paolo, Chiarazzo Cinzia, Maggio GabrieleDi, Longhitano Laura, Manusia Mario, Cartenì Giacomo, Nappi Oscar, Micheli Pietro, Leo Luigi, Rossi Sabrina, Cassano Alessandra, Tommaselli Eugenio, Giordano Guido, Sponziello Francesco, Marino Antonella, Rinaldi Antonio, Romito Sante, Muda Andrea Onetti, Lorusso Vito, Leo Silvana, Barni Sandro, Grimaldi Giuseppe, Aieta Michele
机构信息
Medical Oncology, Department of Clinical and Experimental Medicine "F. Magrassi", Universitá degli Studi della Campania "Luigi Vanvitelli" , Naples, Italy.
Medical Oncology, Department of Clinical and Experimental Medicine "F. Magrassi", Universitá degli Studi della Campania "Luigi Vanvitelli" , Naples, Italy.
出版信息
ESMO Open. 2017 Feb 20;1(6):e000086. doi: 10.1136/esmoopen-2016-000086. eCollection 2016.
BACKGROUND
In the cetuximab after progression in KRAS wild-type colorectal cancer patients (CAPRI) trial patients with metastatic colorectal cancer (mCRC) received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) and cetuximab in first line followed by 5-Fluorouracil, folinic acid, oxaliplatin (FOLFOX) with or without cetuximab until progression. Limited data are available on the efficacy and safety of anti-epidermal growth factor receptor (anti-EGFR) agents on elderly patients with mCRC. In the current study we evaluated the efficacy and safety of FOLFIRI plus cetuximab in age-defined subgroups.
METHODS
A post-hoc analysis was performed in CAPRI trial patients; outcomes (progression-free survival (PFS), overall response rate (ORR), safety) were analysed by age-groups and stratified according to molecular characterisation. 3 age cut-offs were used to define the elderly population (≥65; ≥70 and ≥75 years).
RESULTS
340 patients with mCRC were treated in first line with FOLFIRI plus cetuximab. Among those, 154 patients were >65 years, 86 >70 years and 35 >75 years. Next-generation sequencing (NGS) was performed in 182 patients. Among them, 87 patients were >65 years, 46 >70 and 17 >75. 104 of 182 patients were wild type (WT) for KRAS, NRAS, BRAF, PIK3CA genes. In the quadruple WT group, 51 patients were ≥65 years; 29 were ≥70; 9 were ≥75. Median PFS was similar within the age-subgroups in the intention-to-treat population, NGS cohort and quadruple WT patients, respectively. Likewise, ORR was not significantly different among age-subgroups in the 3 populations. Safety profile was acceptable and similarly reported among all age-groups, with the exception of grade ≥3 diarrhoea (55% vs 25%, p=0.04) and neutropaenia (75% vs 37%, p=0.03) in patients ≥75 years and grade ≥3 fatigue (31% vs 20%, p=0.01) in patients <75 years.
CONCLUSIONS
Tolerability of cetuximab plus FOLFIRI was acceptable in elderly patients. Similar ORR and PFS were observed according to age-groups. No differences in adverse events were reported among the defined subgroups with the exception of higher incidence of grade ≥3 diarrhoea and neutropaenia in patients ≥75 years and grade ≥3 fatigue in patients <75 years.
TRIAL REGISTRATION NUMBER
2009-014041-81.
背景
在KRAS野生型结直肠癌患者西妥昔单抗进展后（CAPRI）试验中，转移性结直肠癌（mCRC）患者一线接受5-氟尿嘧啶、亚叶酸钙和伊立替康（FOLFIRI）及西妥昔单抗治疗，随后接受含或不含西妥昔单抗的5-氟尿嘧啶、亚叶酸钙、奥沙利铂（FOLFOX）治疗，直至疾病进展。关于抗表皮生长因子受体（anti-EGFR）药物对老年mCRC患者疗效和安全性的可用数据有限。在本研究中，我们评估了FOLFIRI联合西妥昔单抗在按年龄定义的亚组中的疗效和安全性。
方法
对CAPRI试验患者进行事后分析；按年龄组分析结局（无进展生存期（PFS）、总缓解率（ORR）、安全性），并根据分子特征进行分层。采用3个年龄切点来定义老年人群（≥65岁；≥70岁和≥75岁）。
结果
340例mCRC患者一线接受FOLFIRI联合西妥昔单抗治疗。其中，154例患者年龄>65岁，86例>70岁，35例>75岁。182例患者进行了二代测序（NGS）。其中，87例患者年龄>65岁，46例>70岁，17例>75岁。182例患者中有104例KRAS、NRAS、BRAF、PIK3CA基因野生型（WT）。在四重WT组中，51例患者≥65岁；29例≥70岁；9例≥75岁。在意向性治疗人群、NGS队列和四重WT患者中，年龄亚组内的中位PFS相似。同样，3组人群中各年龄亚组的ORR无显著差异。安全性可接受，各年龄组报告相似，≥75岁患者≥3级腹泻（55%对25%，p=0.04）和中性粒细胞减少（75%对37%，p=0.03）以及<75岁患者≥3级疲劳（31%对20%，p=0.01）除外。
结论
西妥昔单抗联合FOLFIRI在老年患者中的耐受性可接受。各年龄组的ORR和PFS相似。除≥75岁患者≥3级腹泻和中性粒细胞减少发生率较高以及<75岁患者≥3级疲劳发生率较高外，各定义亚组的不良事件无差异。
试验注册号
2009-014041-81。
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