TY - JOUR
T1 - Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 5-Fluorouracil, and Leucovorin Versus Oxaliplatin, 5-Fluorouracil, Leucovorin, and Bevacizumab for Patients with Stage II or III Rectal Cancer Receiving Preoperative Chemoradiation
T2 - A Trial of the ECOG-ACRIN Research Group (E5204)
AU - Chakravarthy, A. Bapsi
AU - Zhao, Fengmin
AU - Meropol, Neal J.
AU - Flynn, Patrick J.
AU - Wagner, Lynne I.
AU - Sloan, Jeffrey
AU - Diasio, Robert B.
AU - Mitchell, Edith P.
AU - Catalano, Paul
AU - Giantonio, Bruce J.
AU - Catalano, Robert B.
AU - Haller, Daniel G.
AU - Awan, Rashid A.
AU - Mulcahy, Mary F.
AU - O'Brien, Timothy E.
AU - Santala, Roger
AU - Cripps, Christine
AU - Weis, John R.
AU - Atkins, James N.
AU - Leichman, Cynthia G.
AU - Petrelli, Nicholas J.
AU - Sinicrope, Frank A.
AU - Brierley, James D.
AU - Tepper, Joel E.
AU - O'Dwyer, Peter J.
AU - Sigurdson, Elin R.
AU - Hamilton, Stanley R.
AU - Cella, David
AU - Benson, Al B.
N1 - Publisher Copyright:
© AlphaMed Press 2019
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Background: The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum. Subjects, Materials, and Methods: Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with bevacizumab (Arm B) administered every 2 weeks for 12 cycles. Results: E5204 registered only 355 patients (17% of planned accrual goal) as it was terminated prematurely owing to poor accrual. At a median follow-up of 72 months, there was no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related grade ≥ 3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a higher proportion of patients who discontinued therapy early as a result of AEs and patient withdrawal than did Arm A (32.4% vs. 21.5%, p =.029).The most common grade 3–4 treatment-related AEs were neutropenia, leukopenia, neuropathy, diarrhea (without prior colostomy), and fatigue. Conclusion: At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer. Implications for Practice: At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local control rates, the risk of distant metastases and the need to further improve quality of life remain a challenge. Strategies combining novel agents with chemoradiation to improve both distant and local control are needed.
AB - Background: The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum. Subjects, Materials, and Methods: Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with bevacizumab (Arm B) administered every 2 weeks for 12 cycles. Results: E5204 registered only 355 patients (17% of planned accrual goal) as it was terminated prematurely owing to poor accrual. At a median follow-up of 72 months, there was no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related grade ≥ 3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a higher proportion of patients who discontinued therapy early as a result of AEs and patient withdrawal than did Arm A (32.4% vs. 21.5%, p =.029).The most common grade 3–4 treatment-related AEs were neutropenia, leukopenia, neuropathy, diarrhea (without prior colostomy), and fatigue. Conclusion: At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer. Implications for Practice: At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local control rates, the risk of distant metastases and the need to further improve quality of life remain a challenge. Strategies combining novel agents with chemoradiation to improve both distant and local control are needed.
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Bevacizumab/therapeutic use
KW - Chemotherapy, Adjuvant
KW - Disease-Free Survival
KW - Fluorouracil/therapeutic use
KW - Humans
KW - Leucovorin/therapeutic use
KW - Neoplasm Staging
KW - Organoplatinum Compounds/therapeutic use
KW - Oxaliplatin/therapeutic use
KW - Quality of Life
KW - Rectal Neoplasms/drug therapy
UR - http://www.scopus.com/inward/record.url?scp=85077031070&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2019-0437
DO - 10.1634/theoncologist.2019-0437
M3 - Article
C2 - 31852811
AN - SCOPUS:85077031070
SN - 1083-7159
VL - 25
SP - e798-e807
JO - Oncologist
JF - Oncologist
IS - 5
ER -