AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fl...AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117). RESULTS: No significant difference was found between treatment arms A and B in the progression-free survival (PFS) rate at 9 mo, 45% vs 34%; median PFS, 8.6 mo vs 8.3 mo [hazard ratio (HR) = 1.06]; overall response rate (ORR) 43% vs 45% [odds ratio (OR) = 0.93] and median overall survival (OS), 17.4 mo vs 18.9 mo (HR = 0.98). Patients with KRAS wild-type tumors demonstrated improved PFS (HR = 0.55, P = 0.0051), OS, (HR = 0.62, P = 0.0296) and ORR (53% vs 36%) and in arm A, improved PFS (HR = 0.49, P = 0.0196), OS (HR = 0.48, P = 0.0201) and ORR (56%vs 30%), compared with patients with KRAS mutated tumors. In arm B no significant differences were found in efficacy by KRAS mutation status. Treatment in arms A and B was generally well tolerated. CONCLUSION: This study confirms that combinations of cetuximab with FOLFOX6 or FOLFIRI are effective and significantly improve clinical outcome in KRAS wild-type compared with KRAS mutated mCRC.展开更多
Objective： Advances in high-throughput genomic profiling and the development of new targeted therapies improve patient＇s survival. In gastrointestinal （GI） malignancies, the concept of personalized medicine （PM）...Objective： Advances in high-throughput genomic profiling and the development of new targeted therapies improve patient＇s survival. In gastrointestinal （GI） malignancies, the concept of personalized medicine （PM） was not investigated so far. The aim of this prospective study was to evaluate the efficacy of a personalized treatment in GI patients who failed standard treatment. Methods： Out of the original prospective clinical phase II EXACT trial, 21 （38%） GI cancer patients who had no further treatment options were identified. A molecular profile （MP） via a 50 gene next generation sequencing （NGS） panel in combination with immunohistochemistry （IHC） was conducted using real-time biopsy tumor material. Results were discussed by a multidisciplinary team （MDT） to translate the individual MP in an experimental treatment. Results： Of the 55 patients originally included in the EXACT trial, 21 （38%） suffered from GI malignancies. The final analysis showed that 15 （71%） patients had experienced a longer progression-free survival （PFS） upon experimental targeted treatment （124 d, quartiles 70/193 d）, when compared with the PFS achieved by the previous conventional therapy （62 d, quartiles 55/83 d） （P=0.014）. Thirteen （62%） patients receiving targeted treatment experienced a disease control according to Response Evaluation Criteria in Solid Tumors （RECIST）. Median overall survival （OS） from the start of experimental therapy to time of censoring or death was 193 d （quartiles 115/374 d）. Conclusions： PM was not investigated in GI malignancies so far in a prospective trial. This study shows that treatment based on real-time molecular tumor profiling led to a superior clinical benefit, and survival as well as response was significantly improved when compared with previous standard medications.展开更多
文摘AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117). RESULTS: No significant difference was found between treatment arms A and B in the progression-free survival (PFS) rate at 9 mo, 45% vs 34%; median PFS, 8.6 mo vs 8.3 mo [hazard ratio (HR) = 1.06]; overall response rate (ORR) 43% vs 45% [odds ratio (OR) = 0.93] and median overall survival (OS), 17.4 mo vs 18.9 mo (HR = 0.98). Patients with KRAS wild-type tumors demonstrated improved PFS (HR = 0.55, P = 0.0051), OS, (HR = 0.62, P = 0.0296) and ORR (53% vs 36%) and in arm A, improved PFS (HR = 0.49, P = 0.0196), OS (HR = 0.48, P = 0.0201) and ORR (56%vs 30%), compared with patients with KRAS mutated tumors. In arm B no significant differences were found in efficacy by KRAS mutation status. Treatment in arms A and B was generally well tolerated. CONCLUSION: This study confirms that combinations of cetuximab with FOLFOX6 or FOLFIRI are effective and significantly improve clinical outcome in KRAS wild-type compared with KRAS mutated mCRC.
文摘Objective： Advances in high-throughput genomic profiling and the development of new targeted therapies improve patient＇s survival. In gastrointestinal （GI） malignancies, the concept of personalized medicine （PM） was not investigated so far. The aim of this prospective study was to evaluate the efficacy of a personalized treatment in GI patients who failed standard treatment. Methods： Out of the original prospective clinical phase II EXACT trial, 21 （38%） GI cancer patients who had no further treatment options were identified. A molecular profile （MP） via a 50 gene next generation sequencing （NGS） panel in combination with immunohistochemistry （IHC） was conducted using real-time biopsy tumor material. Results were discussed by a multidisciplinary team （MDT） to translate the individual MP in an experimental treatment. Results： Of the 55 patients originally included in the EXACT trial, 21 （38%） suffered from GI malignancies. The final analysis showed that 15 （71%） patients had experienced a longer progression-free survival （PFS） upon experimental targeted treatment （124 d, quartiles 70/193 d）, when compared with the PFS achieved by the previous conventional therapy （62 d, quartiles 55/83 d） （P=0.014）. Thirteen （62%） patients receiving targeted treatment experienced a disease control according to Response Evaluation Criteria in Solid Tumors （RECIST）. Median overall survival （OS） from the start of experimental therapy to time of censoring or death was 193 d （quartiles 115/374 d）. Conclusions： PM was not investigated in GI malignancies so far in a prospective trial. This study shows that treatment based on real-time molecular tumor profiling led to a superior clinical benefit, and survival as well as response was significantly improved when compared with previous standard medications.
