TY - JOUR
T1 - Cetuximab Alone or With Irinotecan for Resistant KRAS-, NRAS-, BRAF- and PIK3CA-wild-type Metastatic Colorectal Cancer
T2 - The AGITG Randomized Phase II ICECREAM Study
AU - Shapiro, Jeremy D.
AU - Thavaneswaran, Subotheni
AU - Underhill, Craig R.
AU - Robledo, Kristy P.
AU - Karapetis, Christos S.
AU - Day, Fiona L.
AU - Nott, Louise M.
AU - Jefford, Michael
AU - Chantrill, Lorraine A.
AU - Pavlakis, Nick
AU - Tebbutt, Niall C.
AU - Price, Timothy J.
AU - Khasraw, Mustafa
AU - Van Hazel, Guy A.
AU - Waring, Paul M.
AU - Tejpar, Sabine
AU - Simes, John
AU - Gebski, Val J.
AU - Desai, Jayesh
AU - Segelov, Eva
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Most unresectable metastatic colon cancer remains incurable, with a median survival of less than 3 years. Molecularly targeted therapies have recently been developed; in particular, monoclonal antibodies against the epidermal growth factor receptor, which are efficacious in 40% to 60% of chemotherapy-resistant patients with wild-type KRAS. This study shows that cetuximab plus irinotecan, compared with cetuximab alone, increases the response rate and delays progression in irinotecan-resistant RAS wild-type colorectal cancer. Background: The Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation (ICECREAM) study assessed the efficacy of cetuximab monotherapy compared with cetuximab combined with chemotherapy for quadruple wild-type (KRAS, NRAS, BRAF, or P13KCA exon 20) metastatic colorectal cancer. Patients and Methods: Patients were enrolled in an open-label, multicenter, phase II trial and randomly assigned to cetuximab 400 mg/m2, then 250 mg/m2 cetuximab weekly, with or without irinotecan 180 mg/m2 every 2 weeks. The primary endpoint was 6-month progression-free survival; secondary endpoints were response rate, overall survival, toxicity, and quality of life. Results: From 2012 to 2016, 48 patients were recruited. Two were ineligible, and 2 were not evaluable for response. Characteristics were balanced, except gender (male, 62% vs. 72%) and primary sidedness (left, 95% vs. 68%). For cetuximab compared with cetuximab-irinotecan, progression-free survival was 14% versus 41% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P =.008); response rate was 10% (2 partial responses) versus 38% (1 complete, 8 partial); P =.04. Grade 3 to 4 toxicities were less with cetuximab monotherapy (23% vs. 50%); global and specific quality of life scores did not differ. Conclusion: In comparison with cetuximab alone, cetuximab plus irinotecan increases the response rate and delays progression in irinotecan-resistant RAS wild-type colorectal cancer. This echoes data from molecularly unselected patients.
AB - Most unresectable metastatic colon cancer remains incurable, with a median survival of less than 3 years. Molecularly targeted therapies have recently been developed; in particular, monoclonal antibodies against the epidermal growth factor receptor, which are efficacious in 40% to 60% of chemotherapy-resistant patients with wild-type KRAS. This study shows that cetuximab plus irinotecan, compared with cetuximab alone, increases the response rate and delays progression in irinotecan-resistant RAS wild-type colorectal cancer. Background: The Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation (ICECREAM) study assessed the efficacy of cetuximab monotherapy compared with cetuximab combined with chemotherapy for quadruple wild-type (KRAS, NRAS, BRAF, or P13KCA exon 20) metastatic colorectal cancer. Patients and Methods: Patients were enrolled in an open-label, multicenter, phase II trial and randomly assigned to cetuximab 400 mg/m2, then 250 mg/m2 cetuximab weekly, with or without irinotecan 180 mg/m2 every 2 weeks. The primary endpoint was 6-month progression-free survival; secondary endpoints were response rate, overall survival, toxicity, and quality of life. Results: From 2012 to 2016, 48 patients were recruited. Two were ineligible, and 2 were not evaluable for response. Characteristics were balanced, except gender (male, 62% vs. 72%) and primary sidedness (left, 95% vs. 68%). For cetuximab compared with cetuximab-irinotecan, progression-free survival was 14% versus 41% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P =.008); response rate was 10% (2 partial responses) versus 38% (1 complete, 8 partial); P =.04. Grade 3 to 4 toxicities were less with cetuximab monotherapy (23% vs. 50%); global and specific quality of life scores did not differ. Conclusion: In comparison with cetuximab alone, cetuximab plus irinotecan increases the response rate and delays progression in irinotecan-resistant RAS wild-type colorectal cancer. This echoes data from molecularly unselected patients.
KW - Cetuximab
KW - Chemotherapy colon cancer
KW - Irinotecan
KW - RAS
UR - http://www.scopus.com/inward/record.url?scp=85049086171&partnerID=8YFLogxK
U2 - 10.1016/j.clcc.2018.06.002
DO - 10.1016/j.clcc.2018.06.002
M3 - Article
C2 - 30463680
AN - SCOPUS:85049086171
SN - 1533-0028
VL - 17
SP - 313
EP - 319
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
IS - 4
ER -
