Cathy Eng, MD, FACP, the Sophie Caroline Steves Distinguished Professor in Cancer Research at The University of Texas MD Anderson Cancer Center, Houston, said the trial demonstrates “the challenge of analyzing six individually conducted studies in a pooled analysis.”
The final duration of oxaliplatin-based therapy should be a continuous matter of discussion between the physician and the patient based on existing toxicities of therapy.— Cathy Eng, MD, FACP
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The study’s “potential pitfalls,” according to Dr. Eng, are that the pooled analysis is composed of a heterogeneous group of independent trials, three of which have final data pending. TOSCA originally randomized patients to bevacizumab; CALGB 80702 includes a second randomization to celecoxib for improved disease-free survival and to date remains blinded. Regardless, all stage III patients from these two trials were included in the pooled analysis, not just the placebo patients. “More mature data are warranted as well as toxicity and compliance for the remaining three trials,” she said. She also noted that the combined subgroup findings came from post hoc analyses.
She emphasized that for low-risk patients, 3 months of FOLFOX was not proven to be noninferior to 6 months, as the 95% confidence interval surpassed the upper boundary threshold of 1.26. For high-risk patients, 3 months of FOLFOX was “clearly inferior,” with a hazard ratio of 1.20 and upper boundary of 1.35. CAPOX, however, was determined to be noninferior overall, but it was also not proven noninferior in high-risk patients, since the upper boundary limit was 1.17. The definition of “low risk” was based solely on T and N stage.
‘Immense Implications’
“Based on the information provided from the IDEA pooled analysis to date, in regard to the primary objective, 3 months of adjuvant oxaliplatin-based chemotherapy is not noninferior to 6 months for disease-free survival. CAPOX appears noninferior in T1–3, N1 patients, but this is largely based on one trial (SCOT), which had incomplete capture of serious adverse events,” she said. The SCOT trial included 1,330 patients, and its hazard ratio of 0.94 favored 3 months of treatment.
Alfred Neugut, MD, PhD
Alfred Neugut, MD, PhD, of NewYork-Presbyterian/Columbia University Medical Center, agreed that “the results are not as clear as the investigators suggested,” and they appeared to be skewed by the 40% of patients who received CAPOX. He did think that lower-risk patients might be as well off with 3 months as 6 months of chemotherapy.
“There are about 40,000 stage III colon cancer patients diagnosed annually in the United States, so the study’s implications are immense,” he added.
Dr. Eng, in her discussion, concluded that while 6 months of adjuvant oxaliplatin-based chemotherapy remains the standard of care for all stage III patients, “In reality, few patients are able to receive all 6 months due to treatment-related serious adverse events, notably dose-limiting neuropathy. The final duration of oxaliplatin-based therapy should be a continuous matter of discussion between the physician and the patient based on existing toxicities of therapy.” ■
DISCLOSURE: Drs. Eng and Neugut reported no conflicts of interest.
