Open AccessIntergroup 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: A Trial of the ECOG‐ACRIN Research Group (E5204)
Author(s) -
Chakravarthy A. Bapsi,
Zhao Fengmin,
Meropol Neal J.,
Flynn Patrick J.,
Wagner Lynne I.,
Sloan Jeffrey,
Diasio Robert B.,
Mitchell Edith P.,
Catalano Paul,
Giantonio Bruce J.,
Catalano Robert B.,
Haller Daniel G.,
Awan Rashid A.,
Mulcahy Mary F.,
O'Brien Timothy E.,
Santala Roger,
Cripps Christine,
Weis John R.,
Atkins James N.,
Leichman Cynthia G.,
Petrelli Nicholas J.,
Sinicrope Frank A.,
Brierley James D.,
Tepper Joel E.,
O'Dwyer Peter J.,
Sigurdson Elin R.,
Hamilton Stanley R.,
Cella David,
Benson Al B.
Publication year - 2020
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2019-0437
Subject(s) - medicine , bevacizumab , oxaliplatin , fluorouracil , colorectal cancer , clinical endpoint , surgery , neutropenia , leukopenia , chemotherapy , gastroenterology , randomized controlled trial , cancer
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.