(ChemotherapyAdvisor) – Final results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) phase 2 prospective, single-arm study of primary systemic chemotherapy with 5-fluorouracil, oxaliplatin (mFOLFOX6) and bevacizumab has found that patients with unresectable stage IV colorectal cancer can be spared initial noncurative resection of their asymptomatic intact primary tumor (IPT), investigators reported in the Journal of Clinical Oncology online August 6.
“The NSABP investigators are to be commended for performing the only modern prospective multi-institutional study that specifically addresses the issue of primary tumor resection in patients with asymptomatic stage IV colorectal cancer,” George J. Chang, MD, MS, of the University of Texas MD Anderson Cancer Center, Houston, TX, in an accompanying editorial also online August 6. “Whereas recent treatment patterns have been influenced by strong patient and provider biases, there is now additional evidence supporting the safety of systemic chemotherapy as the initial primary treatment approach for carefully selected asymptomatic patients, avoiding the need for and the morbidity risk of noncurative resection.”
Median follow-up in the NSABP Trial C-10 was 20.7 months. Median age of the patients was 58 years and 52% were female. A total of 12 patients (14%) had major morbidity related to their IPT; 10 required surgery, 8 for obstruction, 1 for perforation, and 1 for abdominal pain; 2 patients died.
Cumulative incidence of major morbidity at 24 months was 16.3%. “Eleven IPTs were resected without a morbidity event, 8 for attempted cure and 3 for other reasons,” Laurence E. McCahill, MD, of Lacks Cancer Center, St. Mary’s Health Care, Michigan State University, Grand Rapids, MI, and colleagues wrote. Two patients had minor morbidity events only, 1 hospitalization and 1 nonsurgical intervention. Median overall survival was 19.9 months (95% CI, 15.0–27.2 months).
“The challenges of managing unresectable metastatic colon cancer in the setting of an asymptomatic IPT have been an area of intense debate for the last decade,” the investigators wrote. “We believe this approach of primary systemic treatment with expectant observation of the IPT should define a new standard of care.”
Dr. Chang noted, “…more questions remain and additional study is needed to help us understand how best to select patients and optimize the available treatment modalities, including surgery, to improve outcomes and prevent subsequent morbidity.” One question: how best to define “asymptomatic” in a given patient, in that the study took more than 3 years to accrue 86 eligible patients across 29 different institutions.