Cetuximab plus irinotecan,fluorouracil,and leucovorin(FOLFIRI)represents a first-line therapeutic standard for RAS/BRAF wild-type metastatic colorectal cancer(mCRC)patients.Despite this established approach,cetuximab...Cetuximab plus irinotecan,fluorouracil,and leucovorin(FOLFIRI)represents a first-line therapeutic standard for RAS/BRAF wild-type metastatic colorectal cancer(mCRC)patients.Despite this established approach,cetuximabβ(CMAB009),as a modified antibody of cetuximab,prospectively selected for dual RAS/BRAF wild-type patients,has not yet been validated in the Chinese mCRC patients through phase 3 trial.In this study(ClinicalTrials.gov identifier:NCT03206151),patients with RAS/BRAF wild-type mCRC who were not suitable for radical resection were randomly assigned in a 1:1 ratio to receive cetuximabβplus FOLFIRI or FOLFIRI alone.The primary endpoint was blinded independent review committee-assessed progression-free survival(PFS).The secondary endpoints included overall survival(OS),objective response rate(ORR),disease control rate(DCR),surgery rate for metastasis and R0 resection rate,and safety.From January 4,2018 to September 2,2021,a total of 505 eligible patients were enrolled and received study treatment;the median follow-up duration was 8.7 months(95%confidence interval[Cl],7.77 to 9.29)and 5.9 months(95%CI,5.63 to 6.65)in cetuximabβplus FOLFIRI group and FOLFIRI group,respectively.Compared to FOLFIRI alone,cetuximabβplus FOLFIRI demonstrated statistically significant improvements in median PFS(13.1 vs.9.6 months,hazard ratio[HR],0.639;95%CI,0.468 to 0.872;P=0.004),median OS(28.3 vs.23.1 months,HR,0.729;95%CI,0.551 to 0.965;P=0.024),and ORR(69.1%vs.42.3%,odds ratio,3.090;95%CI,2.280 to 4.189;P<0.001).Cetuximabβplus FOLFIRI exhibited manageable toxicity without novel safety signals.This study demonstrated that cetuximabβplus FOLFIRI provided significant clinical benefits as a first-line treatment for patients with RAS/BRAF wild-type mCRC.Compared to FOLFIRI alone,cetuximabβplus FOLFIRI therapy led to prolonged median PFS and OS while maintaining a manageable safety profle,offering a new treatment option for this patient population.展开更多
BACKGROUND Metastatic colorectal cancer(mCRC)treatment has been evolving and increasingly driven by tumor biology and gene expression analysis.Rechallenge with epidermal growth factor receptor(EGFR)inhibitors(anti-EGF...BACKGROUND Metastatic colorectal cancer(mCRC)treatment has been evolving and increasingly driven by tumor biology and gene expression analysis.Rechallenge with epidermal growth factor receptor(EGFR)inhibitors(anti-EGFR)represents a promising strategy for patients with RAS wild-type(RAS-wt)mCRC and circulating tumor DNA has emerged as a potential selection strategy.Herein,we report the case of a RAS-wt mCRC patient who had a successful response to cetuximab rechallenge.CASE SUMMARY Our patient was diagnosed with stage IV RAS-wt,microsatellite-stable rectosigmoid junction adenocarcinoma.He was started on first-line treatment with FOLFIRI and cetuximab and achieved partial response,allowing for a left hepatectomy(R0),followed by post-operative chemotherapy and an anterior resection;progression-free survival(PFS)of 16 months was obtained.Due to hepatic and nodal relapse,second-line treatment with FOLFOX and bevacizumab was started with partial response;metastasectomy was performed(R0),achieving a PFS of 11 months.After a 15 months anti-EGFR-free interval,FOLFIRI and cetuximab were reintroduced upon disease progression,again with partial response and a PFS of 16 months.Following extensive hepatic relapse,cetuximab was reintroduced and a marked clinical and analytical improvement was seen,after only one cycle.RASwt status was confirmed on circulating tumor DNA.The patient’s overall survival exceeded 5 years.CONCLUSION Our case provides real-world data to support cetuximab rechallenge in later lines of RAS-wt mCRC treatment.展开更多
文摘Cetuximab plus irinotecan,fluorouracil,and leucovorin(FOLFIRI)represents a first-line therapeutic standard for RAS/BRAF wild-type metastatic colorectal cancer(mCRC)patients.Despite this established approach,cetuximabβ(CMAB009),as a modified antibody of cetuximab,prospectively selected for dual RAS/BRAF wild-type patients,has not yet been validated in the Chinese mCRC patients through phase 3 trial.In this study(ClinicalTrials.gov identifier:NCT03206151),patients with RAS/BRAF wild-type mCRC who were not suitable for radical resection were randomly assigned in a 1:1 ratio to receive cetuximabβplus FOLFIRI or FOLFIRI alone.The primary endpoint was blinded independent review committee-assessed progression-free survival(PFS).The secondary endpoints included overall survival(OS),objective response rate(ORR),disease control rate(DCR),surgery rate for metastasis and R0 resection rate,and safety.From January 4,2018 to September 2,2021,a total of 505 eligible patients were enrolled and received study treatment;the median follow-up duration was 8.7 months(95%confidence interval[Cl],7.77 to 9.29)and 5.9 months(95%CI,5.63 to 6.65)in cetuximabβplus FOLFIRI group and FOLFIRI group,respectively.Compared to FOLFIRI alone,cetuximabβplus FOLFIRI demonstrated statistically significant improvements in median PFS(13.1 vs.9.6 months,hazard ratio[HR],0.639;95%CI,0.468 to 0.872;P=0.004),median OS(28.3 vs.23.1 months,HR,0.729;95%CI,0.551 to 0.965;P=0.024),and ORR(69.1%vs.42.3%,odds ratio,3.090;95%CI,2.280 to 4.189;P<0.001).Cetuximabβplus FOLFIRI exhibited manageable toxicity without novel safety signals.This study demonstrated that cetuximabβplus FOLFIRI provided significant clinical benefits as a first-line treatment for patients with RAS/BRAF wild-type mCRC.Compared to FOLFIRI alone,cetuximabβplus FOLFIRI therapy led to prolonged median PFS and OS while maintaining a manageable safety profle,offering a new treatment option for this patient population.
文摘BACKGROUND Metastatic colorectal cancer(mCRC)treatment has been evolving and increasingly driven by tumor biology and gene expression analysis.Rechallenge with epidermal growth factor receptor(EGFR)inhibitors(anti-EGFR)represents a promising strategy for patients with RAS wild-type(RAS-wt)mCRC and circulating tumor DNA has emerged as a potential selection strategy.Herein,we report the case of a RAS-wt mCRC patient who had a successful response to cetuximab rechallenge.CASE SUMMARY Our patient was diagnosed with stage IV RAS-wt,microsatellite-stable rectosigmoid junction adenocarcinoma.He was started on first-line treatment with FOLFIRI and cetuximab and achieved partial response,allowing for a left hepatectomy(R0),followed by post-operative chemotherapy and an anterior resection;progression-free survival(PFS)of 16 months was obtained.Due to hepatic and nodal relapse,second-line treatment with FOLFOX and bevacizumab was started with partial response;metastasectomy was performed(R0),achieving a PFS of 11 months.After a 15 months anti-EGFR-free interval,FOLFIRI and cetuximab were reintroduced upon disease progression,again with partial response and a PFS of 16 months.Following extensive hepatic relapse,cetuximab was reintroduced and a marked clinical and analytical improvement was seen,after only one cycle.RASwt status was confirmed on circulating tumor DNA.The patient’s overall survival exceeded 5 years.CONCLUSION Our case provides real-world data to support cetuximab rechallenge in later lines of RAS-wt mCRC treatment.
